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A case report of male breast cancer in a very young patient: What is changing?

  • Marcelo Madeira 1 , 2 ,
  • André Mattar 1 , 3 ,
  • Rodrigo José Barata Passos 1 ,
  • Caroline Dornelles Mora 3 ,
  • Luiz Henrique Beralde Vilar Mamede 2 ,
  • Viviane Hatsumi Kishino 2 ,
  • Thomas Zurga Markus Torres 2 ,
  • Andressa Fernandes Rodrigues de Sá 2 ,
  • Roberto Euzébio dos Santos 2 , 3 &
  • Luiz Henrique Gebrim 1 , 3  

World Journal of Surgical Oncology volume  9 , Article number:  16 ( 2011 ) Cite this article

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Male breast cancer accounts for 1% of all breast cancer cases, and men tend to be diagnosed at an older age than women (mean age is about 67 years). Several risk factors have been identified, such as genetic and hormonal abnormalities.

The present study reported the case of a 25-year-old man who was diagnosed with an advanced invasive ductal carcinoma; however, he did not have any important risk factors.

Even though more data is emerging about this disease, more efforts to understand risk factors, treatment options and survival benefits are needed. In this case, we discussed the risk factors as well as the impaired fertility associated with breast cancer therapies.

Breast cancer in men is rare, and it accounts for about 1% of all malignant breast neoplasm cases [ 1 , 2 ]. The estimated incidence is 1 case for each 100,000 men. In the United States, about 1,910 new cases were diagnosed in 2009, and 440 of these cases resulted in death [ 3 ]. Among the histologic types, invasive ductal carcinoma is the most prevalent breast cancer in males, with an incidence varying from 65 to 95% [ 2 , 4 ].

Male breast cancer has unimodal age-frequency distribution with a peak incidence at 71 years old. Conversely, female breast cancer has a bimodal age-frequency distribution with early-onset and late-onset peak incidences at 52 and 72 years old, respectively [ 5 ].

This study examined a 25-year-old man without important risk factors who was diagnosed with invasive ductal carcinoma. Although it is rare, there have been instances of breast cancer in younger males [ 6 ]. We evaluated the main aspects of the epidemiology of breast neoplasm in men and the best approach for treatment.

Case presentation

A 25-year-old Brazilian male was referred to our institution in August 2007 complaining of a breast tumor of progressive growth for the previous eight months. Previous medical and family history did not appear to contribute to the present illness. He denied using drugs or anabolic steroids and did not drink alcohol. The only medication he was taking was phenobarbital, which he had been taking for four years since he presented with two seizure episodes. The patient was a smoker who consumed 10 cigarettes per day. He also reported a normal sexual life, but he did not have children.

Physical examination revealed a 3.5 cm tumor located on the right breast. There was a retraction of the nipple; the nodule, which could be moved, had a hardened consistency and did not adhere to deep planes. The armpits did not present lymphadenopathy.

Mammographic findings consisted of a noncalcified high density mass (Figure 1 ) and breast ultrasonography revealed a hypoechogenic nodule of irregular shape with partially defined limits measuring 17 × 13 × 11 mm in the right breast. The magnetic nuclear resonance imaging showed a retroareolar nodule in the right breast, which corresponded to an expansive process. There were also signs of infiltration of the pectoralis muscle and a small area of retroareolar highlight in the left breast. Final Breast Imaging Reporting and Data System (BI-RADS) category was 5: highly suggestive of malignancy.

figure 1

Mammographic findings. Noncalcified high density mass of right breast .

Fine-needle aspiration and a core biopsy of the lesion were performed, and the diagnosis was invasive ductal carcinoma (Figure 2 ). After a recommended sperm cryopreservation, the patient started neoadjuvant chemotherapy (4 × FEC 100 + 1 cisplatin 75 with adriamycin 60). In February 2008, the patient was submitted to a modified radical mastectomy (right breast) and retroareolar lumpectomy (left breast) (Figure 3 ).

figure 2

Histological biopsy: invasive ductal carcinoma (hematoxylin-eosin staining) .

figure 3

Surgery . Modified radical mastectomy (right breast) and retroareolar lumpectomy (left breast).

The anatomopathological analysis confirmed the diagnosis of invasive ductal carcinoma with a 3.0-cm lesion in the biggest axle, which was histologic grade 2 and nuclear grade 2. Final breast surgical margins were free, but pectoralis muscle fascia and the nipple were infiltrated. The axillary lymph nodes dissection did not show any signs of cancer (0/8). In addition, immunohistochemical staining of the tumor was positive for estrogen and progesterone receptors, and HER-2 negative (Score 1). Although there were no signs of malignancy or atypical hyperplasia in the left breast tissue, there was fibrosclerosis and benign fibroadipose tissue.

The patient received adjuvant therapy along with radiation therapy (5,000 cGy), and tamoxifen (20 mg/day). Post-therapy follow-up were performed by members of the treatment team and included regular physical examinations and history. Liver function and alkaline phosphatase tests were not indicated during the time the patient was taking endocrine therapy. Although reports have appeared about the dangers of liver damage and hepatoma resulting from tamoxifen administration, results from NSABP studies attest such concerns have not been substantiated [ 7 ].

One year after the radiation therapy ended, the patient presented with cervical and dorsal nodules, jaundice and weight loss (about 20 kg). Evaluation of suspicious recurrent breast cancer included physical exam, the performance of a CBC, platelet count, liver function tests, chest imaging, bone scan and an abdomen ultrasound. Blood tests results were negative for hepatitis A, B and C, serum glutamic oxaloacetic transaminase 241 IU/L (normal range: 10-34), serum alanine aminotransferase 187 IU/L (7-50), lactate dehydrogenase 358 U/L (50-150), total bilirubin 8.69 mg/dl (0.3-1.9), direct bilirubin 8.40 mg/dl (0-0.3) and alkaline phosphatase 959 IU/L (20-140).

In October 2009, the abdominal ultrasonography showed the presence of several hepatic nodules. The general state of the patient was deteriorating. He had a variety of symptoms, including a lower level of consciousness, dysphagia, inappetence, fever, cyanosis, and dyspnea. The patient quickly developed multiple organ failure and died in November 2009.

Because of weakness and quick deterioration of health state of the patient, it was not possible to perform a biopsy documentation of recurrence and determination of hormone receptor status and HER-2 status.

Invasive ductal carcinoma in men presents peculiar features. About 42% of breast cancer cases in men are diagnosed in stage III or IV [ 1 ]. This is probably because men do not seek medical attention for breast masses as quickly as women. In addition, the tumor is usually closer to the skin in males, which increases the likelihood of infiltration into the dermis, which was reported in the present case.

Treatment strategies for male breast cancer are not based on data from randomized clinical studies in men and most treatment recommendations are extrapolated from data in women [ 8 ].

Men with breast carcinoma have a poor prognosis, especially in the younger age group, because most breast enlargements in young men are dismissed as gynecomastia [ 9 , 10 ]. This potential misdiagnosis can result in an unnecessary delay in treatment. The median age of breast cancer diagnosis in men is approximately 65 years old [ 11 ]. Reports of breast cancer in young male patients are rare. Nielsen and Jakobsen described a breast cancer case in a 32-year-old man [ 12 ]. More recently, an invasive cancer case was reported in a 30-year-old patient [ 9 ]. In 2008, Chang et al. described the case of a 16-year-old male with unilateral ductal carcinoma in situ and gynecomastia [ 13 ].

There is a close relation between the BRCA2 gene mutation and male breast cancer. It has also been observed, however, that some cases involve BRCA1 participation [ 14 – 16 ]. Other conditions that have been associated with the occurrence of breast neoplasms in men are cirrhosis [ 17 ], testicular trauma, obesity, radiation therapy exposure, and the use of exogenous estrogen [ 18 ]. In addition to the very young age of the patient in the present report, this patient did not have a family, hormonal, or genetic history that could justify the high risk for breast cancer. Although gynecomastia has been suggested to be present in 6-38% of breast cancer cases in men [ 19 ], it was not evident in our patient.

It is fundamental to consider the history of breast tumors in first-degree relatives because that can be an indicator for increased breast cancer risk. Indeed, genetic diseases such as Klinefelter's syndrome and Cowden's disease have been shown to be related to breast cancer in men [ 1 ].

There is no evidence that suggests that all men need breast magnetic nuclear resonance imaging (MRI). But suspicious MRI lesions in the contralateral breast should be examined. Furthermore, male breast cancer survivors have an increased risk of developing a second primary cancer. The risk of a contralateral breast cancer appears to be higher for men than it is for women [ 20 ]. Some studies indicate that men with breast cancer have a 30-fold increased risk of contralateral breast cancer, much greater than the two- to fourfold risk among women with breast cancer [ 21 ]. The risk of subsequent contralateral breast cancer was highest for men aged less than 50 years at the time of the first cancer diagnosis, which is consistent with studies of women with breast cancer [ 22 , 23 ].

Estrogen receptors and progesterone receptors have been suggested to play a role in breast cancers in men, and they are present in about 90% and 81% of breast cancers in males, respectively [ 4 ]. Furthermore, overexpression of the proto-oncogene HER-2 has been shown to present the worst prognosis for a patient [ 24 ]. Other markers that have been recently studied are p27, MIB-1 and Bcl-2 genes.

Similar to breast cancer cases in women, earlier detection of male breast cancer is correlated with the success of the treatment. Although males have considerably less mammary parenchyma than women, the investigation must be a combination of a clinical exam, mammography, cytology, and percutaneous biopsies [ 25 , 26 ]. The core needle biopsy is important because it enables a definitive diagnosis of invasive breast cancer and the evaluation of estrogen receptors, progesterone receptors, and Her-2 status [ 3 ].

Tamoxifen should still be considered as the optimal adjuvant therapy option for male patients with endocrine responsive disease. The effect regarding rate and overall survival by adjuvant chemotherapy is also far less well studied [ 8 ]. Some studies have demonstrated an improved disease-free and overall survival compared with historical controls using adjuvant anthracycline-based therapies [ 4 , 5 , 27 ].

Because of the high probability of an indefinite period of infertility following chemotherapy, sperm cryopreservation should be recommended for all young patients with cancer prior to the start of chemotherapy. Although treatment and survival represent the primary goals of the clinical approach towards breast cancer patients, the quality of life after treatment, including the possibility of becoming fathers, requires consideration. In addition, sperm cryopreservation is another hope that encourages young patients with cancer during and after treatment [ 28 ].

Breast cancer therapeutics in men must be based on certain parameters, such as tumor size, the presence of estrogen and progesterone receptors, HER-2 expression, and the association with other diseases. Men diagnosed with breast cancer present risk factors, such as chronic hepatopathies, that are directly associated with the neoplasm. In addition, men diagnosed with breast cancer are generally older and present other comorbidities. Due to the smaller size of male mammary parenchyma, the elected surgical treatment is modified radical mastectomy.

Conclusions

Invasive ductal carcinoma in young men is extremely rare; the peak incidence is around the seventh decade of life. Risk factors for male breast cancer include genetic factors and hormonal abnormalities. Despite an absence of a familial history of breast cancer, hormonal abnormalities, or a genetic disease, the male patient in the present study developed breast cancer at a very young age. The causative factors in this patient were unable to be definitively identified. The pathophysiology of breast cancer in males is not adequately understood. As more cases of breast cancer in young male patients are investigated, we may be able to gain a better understanding of the mechanism.

Written informed consent was obtained from the patient's family for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

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Marcelo Madeira, André Mattar, Rodrigo José Barata Passos & Luiz Henrique Gebrim

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Marcelo Madeira, Luiz Henrique Beralde Vilar Mamede, Viviane Hatsumi Kishino, Thomas Zurga Markus Torres, Andressa Fernandes Rodrigues de Sá & Roberto Euzébio dos Santos

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AM, RJBP, CDM and RES took part in the care of the patient. MM, LHBVM, VHK, TZMT and AFRS were responsible for the literature review, design, and writing of the manuscript. LHG was responsible for the manuscript completion and critical review. All authors read and approved the final manuscript.

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Madeira, M., Mattar, A., Passos, R.J.B. et al. A case report of male breast cancer in a very young patient: What is changing?. World J Surg Onc 9 , 16 (2011). https://doi.org/10.1186/1477-7819-9-16

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World Journal of Surgical Oncology

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male breast cancer case study

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  • Published: 07 January 2022

Clinicopathologic characteristics and prognosis for male breast cancer compared to female breast cancer

  • Nan Yao 1   na1 ,
  • Wenzai Shi 2   na1 ,
  • Tong Liu 3 ,
  • Sarah Tan Siyin 4 ,
  • Weiqi Wang 1 ,
  • Ning Duan 1 ,
  • Guoshuai Xu 1 &
  • Jun Qu 1 , 5  

Scientific Reports volume  12 , Article number:  220 ( 2022 ) Cite this article

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Male breast cancer (MBC) is rare. Due to limited information, MBC has always been understudied. We conducted a retrospective population-based cohort study using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. The clinical and biological features of female breast cancer (FBC) patients were compared with MBC patients. Cox regression models and competing risks analyses were used to identify risk factors associated with cancer-related survival in MBC and FBC groups. Results showed that MBC patients suffered from higher TNM stages, tumor grades, and a higher percentage of hormone receptor-positive tumors, compared with FBC patients (all p  < 0.05). In addition, the breast tumor locations varied a lot between males and females ( p  < 0.05). FBC patients were associated with superior overall survival than MBC patients. Results from multivariate cox regression and competing risks analyses showed age, race, T, N, M-stages, tumor grades, estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) overexpression were independent prognosis factors in FBC patients (all p  < 0.05). MBC patients had similar risk factors to FBC patients, but PR and HER-2 status did not independently influence survival (all p  > 0.05). Tumor location was an independent prognostic factor for both gender groups.

Introduction

Breast cancer is one of the most common malignant tumors, and the leading cause of cancer-related death in women worldwide. In 2018, there were an estimated 2.1 million new cases of breast cancer and 627,000 deaths from breast cancer worldwide 1 . Though it is rare, breast cancer in men accounts for 1% of all breast cancer cases 2 , 3 .

Given the low incidence, previous studies on male breast cancer (MBC) have suffered from small sample sizes, short follow-up time, limiting their interpretability. And the therapeutic strategies for MBC patients are commonly extrapolated from those used to treat postmenopausal female breast cancer (FBC) patients 4 , 5 . No existing evidence-based data supports this female-to-male extrapolation. Literature has suggested that MBC has biological differences compared with FBC. MBC patients are typically associated with advanced stages, higher grades, higher prevalence of hormone receptor-positive, and a worse prognosis 6 , 7 , 8 , 9 , 10 , 11 . Furthermore, studies have proposed that MBC patients are insensitive to adjuvant therapy, and an underutilization of therapy in MBC patients compared with FBC patients 12 , 13 . Therefore, it may be inappropriate to adopt the clinical applications of female-to-male extrapolation.

In the current study, we attempt to compare the clinicopathologic characteristics and prognosis between MBC patients and FBC patients by drawing data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Database from the beginning of 2010 to the end of 2014, with the aim of better understanding gender differences and specificity of MBC.

Materials and methods

This is a retrospective cohort study of breast cancer patients diagnosed in the SEER database 8.3.4 from the beginning of 2010 to the end of 2014. SEER collects cancer incidence data from population-based cancer registries covering approximately 34.6% of the U.S. population. It also records data of patients’ clinicopathological characteristics, and vital status during follow-up. Breast cancer cases were identified according to the 3rd edition of the International Classification of Diseases for Oncology (ICD-O-3).

A total of 313,504 patients with breast cancer were identified in the SEER database. Patients were excluded if they had 1) survival month that was 0 or unknown; 2) T0 local disease diagnosis; 3) other malignant tumors. 4) missing information for demographic and tumor characteristics including sex, age, laterality (left, right, bilateral), tumor location, race (white, black, and other), pathological type (ductal, lobular, and other), TNM stage, histological grade (well-differentiated, moderately differentiated, poorly-differentiated and undifferentiated), surgical treatment of breast cancer, estrogen receptor (ER), progesterone receptor (PR), and HER-2. A total of 169,278 patients (1,123 males and 168,155 females) remained in the final analysis (Fig.  1 ). Surgical treatment of breast cancer was defined as patients who received any type of surgical resection of the primary tumor. Histology was classified into three subtypes: ductal, lobular and others including mucinous adenocarcinoma, non-small cell carcinoma, adenocarcinoma and other rare types of cancer. All patients have given prior informed consent to being registered in SEER database.

figure 1

Flow chart of patients’ selection for final analysis.

Statistical analysis

All statistical analyses were performed using SAS statistical software (version 9.4). The characteristics of the subjects with normal distribution were expressed as mean ± standard deviation and compared using t test. Categorical variables were represented as absolute value with percentage and the Chi-square test was used for comparison between male and female patients. Kaplan–Meier survival curves were generated to compare differences in survival probabilities over time between groups, and the equality of these curves was tested using a log-rank statistic.

The interval from the date of cancer diagnosis to the endpoint was calculated as survival time (in months). The endpoint was defined as one of the three events, whichever occurred first: date of breast cancer-related death, date of non-breast cancer related death, or the date used as the cutoff for the study. Cox regression models were generated to describe the relationship between clinicopathologic features and risk of breast cancer-related death among MBC patients and FBC patients.

Non-breast cancer related death may occur before the occurrence of breast cancer-related death during the follow-up period which hinders us from identifying the existence of breast cancer cases. The traditional multivariate COX regression model may markedly overestimate the risk of breast cancer 14 . To avoid overestimation and to improve accuracy, the cause-specific hazard model (CS model) and sub-distribution hazard function model (SD model) were used to calculate the absolute risk of breast cancer-related death. A two-sided p -value < 0.05 was considered statistically significant in this study.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Aerospace Center Hospital and was complied with the Declaration of Helsinki.

Differences in clinical and pathological characteristics between males and females

MBC (n = 1,123/169,278) represented 0.66% of all breast cancers. The common descriptive characteristics of both genders are presented in Table 1 . The median age at diagnosis for MBC was 63.45 ± 10.81 years old compared to 58.96 ± 12.14 years old for FBC ( p  < 0.001). In MBC patients, the race of patients was predominantly white (80.23%), with 14.34% black and 5.43% other races. In FBC patients, 79.19% were white, 11.04% were black and 9.77% were of others races ( p  < 0.001). There was no difference in laterality between men and women ( p  = 0.085). MBC patients tend to have larger tumor sizes ( p  < 0.001), a higher percent of lymph node ( p  < 0.001) and organ metastasis ( p  < 0.001) compared with FBC patients. MBC patients were also more likely to present with advanced grades ( p  < 0.001). In terms of pathological types, 84.86% of MBC patients were invasive ductal carcinoma compared with 77.81% in FBC patients. Lobular carcinomas accounted for only 0.62% of breast cancer in MBC patients by the contract of 8.14% in FBC patients ( p  < 0.001). Compared with FBC patients, MBC patients were more likely to express hormone receptor-positive. 97.42% of men and 82.72% of women had ER-positive tumors ( p  < 0.001). Similarly, MBC patients were more likely to have PR-positive tumors than FBC patients (91.63% vs. 72.46%, p  < 0.001). Compared with FBC patients, MBC patients exhibited a lower percentage of HER-2 overexpression (11.04% vs. 14.68%, p  < 0.001).

Among MBC patients, there were 47.91% of tumors located with the central portion, followed by 15.58% in the upper-outer quadrant, 6.14% in the nipple, 5.16% in the lower-outer quadrant, 4.27% in the upper-inner quadrant, 2.23% in the lower-inner quadrant, 0.09% in the axillary tail, and the remaining 18.61% were classified as overlapping lesion. However, in FBC patients, there were only 5.20% of tumors located in the central portion, and tumors primarily located in the upper-outer accounted for 39.16%. The rest were located in the upper-inner quadrant (14.06%), lower-inner quadrant (6.38%), lower-outer quadrant (8.44%), nipple (0.38%), axillary tail (0.53%), and overlapping lesion (25.86%).

The association of clinicopathologic characteristics with the cancer-related death risk

During the median follow-up of 57 (43–74) months, 116 male patients and 13,140 female patients died from breast cancer. The Kaplan–Meier method showed that the MBC patients had a worse overall survival (OS) than FBC patients. The log-rank test showed a significant difference in the OS between the two groups (log-rank, p  < 0.001, Fig.  2 ).

figure 2

Breast-cancer-specific survival between the MBC and FBC groups.

Multivariate Cox regression models were generated to describe the association between clinicopathological characteristics and risk of death. Among FBC patients, results indicated that age (HR = 1.17, 95% CI: 1.16–1.19), black race (HR = 1.24, 95% CI: 1.19–1.30), higher tumor grades (HR grade2vs. grade1  = 1.79, 95% CI: 1.65–1.93; HR grade3vs. grade1  = 2.98, 95% CI: 2.75–3.23; HR grade4vs. grade1  = 3.01, 95% CI: 2.42–3.73), larger tumor size (HR T2vs.T1  = 2.34, 95% CI: 2.23–2.45; HR T3vs.T1  = 3.46 95% CI: 3.25–3.68; HR T4vs.T1  = 3.81, 95% CI: 3.56–4.08), higher lymph node involvement (HR N1vs.N0  = 1.84, 95% CI: 1.76–1.92; HR N2vs.N0  = 3.06, 95% CI: 2.89–3.24; HR N3vs.N0  = 3.57, 95% CI: 3.36–3.80), distant metastasis (HR = 3.95, 95% CI: 3.74–4.17), and type of histology (HR lobular vs. ductal  = 1.10, 95% CI: 1.03–1.18) were associated with a higher risk of cancer-related death. On the contrary, ER positive (HR = 0.67, 95% CI: 0.64–0.71), PR positive (HR = 0.61, 95% CI: 0.58–0.64), HER-2 positivity (HR = 0.56, 95% CI: 0.54–0.59), and breast surgery (HR = 0.33, 95% CI: 0.31–0.34) were associated with significantly reduced risks of cancer-related death (Table 2 ). Similar results were obtained among MBC patients; however, it was noteworthy that PR (HR = 0.68, 95% CI: 0.35–1.31) and HER-2 status (HR = 0.95, 95% CI: 0.55–1.63) did not appear to independently influence cancer-related survival (Table 2 ). Tumor location was an independent prognostic factor for both MBC and FBC patients. Medial location tumor was associated with a poorer prognosis compared with central and lateral location tumor (HR central vs. medial  = 0.95, 95% CI: 0.92–0.98, HR lateral vs. medial  = 0.93, 95% CI: 0.90–0.97 in females; HR central vs. medial  = 0.44, 95% CI: 0.21–0.94, HR lateral vs. medial  = 0.47, 95% CI: 0.24–0.72 in males).

During the follow up, a total of 9,255 non-breast cancer-related death cases were identified before the occurrence of breast cancer-related death. Tables 3 , 4 summarizes adjusted HRs (95%CI) for the association of clinicopathological characteristics with breast cancer related death after taking competing risk events (none breast cancer-related death) into consideration. The associations of clinicopathological characteristics with breast cancer-related death were attenuated but remained significant both in the CS models and the SD models.

This large-scale population-based study, which makes comparisons between MBC and FBC patients, provides intriguing etiologic and prognostic clues to this disease. Several significant conclusions were made. First, MBC patients have a worse prognosis than FBC patients. Second, there were differences in independent prognostic factors between MBC and FBC patients: PR and HER-2 were independent prognostic factors for FBC but not MBC patients. Finally, breast tumor locations between the two genders were different, which might have an important influence on prognostic results.

In our analysis, MBC patients had a worse overall prognosis than FBC counterparties which was in line with several previous studies. Nahleh et al. found that FBC patients had a significantly longer OS than MBC patients. The median OS for MBC patients was 7.0 years compared with 9.8 years for FBC patients (log-rank test; p  < 0.05) 9 . Similarly, a study including 2,537 MBC patients also demonstrated that MBC patients had a relatively shorter 5-year survival rate than FBC patients 4 . Several explanations may help to explain this phenomenon. Better prognosis in FBC patients is partly due to the introduction of screening, public awareness, diagnosis at an earlier age with fewer complications, advances in treatment, and standardization of treatment regimens in international guidelines. However, the situation in MBC patients differs a lot compared with female counterparts. First, the breast tissue in men is sparser, and a small tumor would be able to invade the breast skin rapidly. The tumor can also be easily drained into the subareolar lymphatic plexus and thus could lead to a high propensity to metastasize 15 . Second, the prevalence of adjuvant therapies for MBC patients is far behind FBC patients. A recent study using the SEER data from 1996 to 2005 demonstrated that there is a 42% decrease in breast cancer-specific mortality among women compared with only a 28% decrease among men, suggesting that the treatments being used in MBC patients are not as effective as they are for FBC patients 10 . Third, the use of adjuvant therapy in MBC patients is not widespread as FBC patients. In a paper that included 10,173 men with HR-positive breast cancer, men were less likely to receive adjuvant endocrine therapy than women (67.3% vs 78.9%, p  < 0.001) 16 . Reliable and widespread use of adjuvant chemotherapy and radiotherapy for men is also lacking 17 , 18 , 19 , 20 . However, among the patients who were treated with surgery in this current study, male patients were more likely to receive mastectomy than tumorectomy (88.77% vs. 11.23%) when compared to female patients (37.84% vs. 62.16%, p  < 0.001). The generally higher rate of mastectomies in men could explain why radiotherapy is less often used.

There may be different risk factors between FBC and MBC especially when it is related to PR and HER-2. A population-based study indicated PR status did not appear to independently influence survival among MBC patients 4 . Matthew J’s study also demonstrated PR status did not affect survival in MBC patients 21 . This may be related to the fact that PR status is not a crucial factor for endocrine therapy, and MBC patients are not as sensitive towards endocrine therapy. Little research has focused on HER-2 expression in men. The effectiveness of trastuzumab in HER-2 overexpressing MBC is unproven 22 . In addition, MBC patients with HER-2 overexpression only comprise a small portion of all MBC patients 23 , 24 , making it difficult to draw a reliable conclusion.

In this current study, the tumor locations between the MBC and FBC patients were markedly different. Among FBC patients, tumors were primarily located in the upper-outer and accounted for 39.16% while other sites in the breast were discovered at lower frequencies, which is in alliance with previous studies 25 , 26 , 27 , 28 . This basic observation of asymmetric occurrence of breast cancer has become well accepted but lacks an adequate scientific explanation. A possible explanation is that the upper-outer quadrant of the breast contains a greater proportion of the epithelial tissue, which has a greater chance to occur cancer 29 . In MBC patients, the central position (nipple and central portion) is dominant which accounted for 54.05%. The upper-outer quadrant only made up 15.58%, which was far below the central position. This discrepancy may be caused by the anatomy of the male breast, as there is a larger volume of epithelial breast tissue in the central portion in men 29 . In addition, the prognostic role of the tumor location is also underappreciated, as almost all breast cancer guidelines do not include tumor location as a prognostic factor 30 , 31 . Yet in our study, tumor location affected the prognosis for both MBC and FBC patients; tumors situated in the medial quadrants of the breast have a worse prognosis compared with those located in lateral quadrants. This finding was compatible with other papers. David K et. al suggested that medial tumor location adversely impacts breast cancer-specific survival and OS in breast cancer patients 32 . Similarly, the Caroline trials indicated that medial location was associated with a 50% excess risk of systemic relapse and breast cancer death compared with lateral tumors 33 .

The poor prognosis of tumors with the internal location may be associated with internal mammary nodes (IMN), which were not conventionally treated. Findings from a previous study have found occult nodal metastases in the internal mammary chain is more likely to be found in tumors with a central or medial location and female breast cancer patients with metastatic axillary nodes 34 . The tumor cell is usually clinically silent in the internal mammary chain, and it might disseminate the disease, especially in node-negative women, who did not receive adjuvant systemic treatment 35 . It has also been observed that 5% of breast cancer patients metastasis to IMNs alone 34 .

Competing risks are common in epidemiological research 35 , 36 . In the current study, cancer-unrelated death occurred before the identification of cancer-related death. In this competing risk setting, traditional Cox regression may overestimate the absolute risk of cancer-related death, because individuals with a competing (and therefore censored) event are considered to be likely to experience events of interest in the future. The CS model and the SD model are different, and the choice of method should be determined by scientific issues. The CS model may be more suitable for studying the cause of the disease, while the SD model can be used to predict individual risks 14 . Future research should be conducted to explore methodological differences and expand tools to understand competitive risk methods for epidemiological data.

The strength of this current study is the large quantity of data regarding MBC and FBC patients, which allows for a reliable extrapolation of the results. Furthermore, we analyzed the tumor location within the breast, which has been rarely focused on. Moreover, competing risk regressions were further used to validate our results, increasing the accuracy of the study. However, the limitations should also be acknowledged. The main limitation of this study was its missing data, especially on antigens identified by monoclonal antibody Ki-67 status, disease-free survival and adjuvant therapy information. Furthermore, the pathologic information was collected from different hospitals and failed to undergo a centralized review. Lastly, because of the special status of the disease, the number of MBC and FBC patients was very asymmetric. However, the bias was minimized as males and females were studied separately.

Conclusions

Our retrospective study showed that MBC has a worse overall prognosis than FBC and the independent prognostic factors between MBC and FBC were not entirely the same. In addition, there are vast differences between genders for tumor location, which should be considered by clinicians as a prognostic factor. MBC should be considered as an independent disease. Future research on MBC is needed in many aspects, including molecular pathology, risk factors, genetic contributions diagnostic and therapeutic tools.

Abbreviations

Male breast cancer

Female breast cancer

Estrogen receptor

Progesterone receptor

Human epidermal growth factor receptor 2

Overall survival

Surveillance, epidemiology, and end results

Internal mammary nodes

Cause-specific hazard model

Sub-distribution hazard function model

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Acknowledgements

We thank all the staff and participants of the SEER database for their important contributions.

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Department of General Surgery, Aerospace Center Hospital, Beijing, 100089, China

Nan Yao, Weiqi Wang, Ning Duan, Guoshuai Xu & Jun Qu

Department of Hepatobiliary Surgery, Peking University International Hospital, Beijing, 100038, China

Department of Gastrointestinal Surgery, Beijing Shijitan Hospital, Beijing, 100038, China

Department of General Surgery, Beijing Children’s Hospital, Beijing, 100038, China

Sarah Tan Siyin

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N.Y., and W.S. executed the study and drafted the manuscript. N.Y., T.L. and S.T.S. participated in the study design and performed the statistical analyses. W.W., N.D. and G.X. contributed to the discussion. J.Q. reviewed the manuscript.

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Yao, N., Shi, W., Liu, T. et al. Clinicopathologic characteristics and prognosis for male breast cancer compared to female breast cancer. Sci Rep 12 , 220 (2022). https://doi.org/10.1038/s41598-021-04342-0

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Introduction

Materials and methods, disclosure of potential conflicts of interest, authors' contributions, acknowledgments, finasteride use and risk of male breast cancer: a case–control study using individual-level registry data from denmark, finland, and sweden.

Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

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Thora M. Kjærulff , Annette K. Ersbøll , Anders Green , Martha Emneus , Klaus Brasso , Peter Iversen , Eero Pukkala , Kristian Bolin , Lau C. Thygesen; Finasteride Use and Risk of Male Breast Cancer: A Case–Control Study Using Individual-Level Registry Data from Denmark, Finland, and Sweden. Cancer Epidemiol Biomarkers Prev 1 May 2019; 28 (5): 980–986. https://doi.org/10.1158/1055-9965.EPI-18-0904

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In case reports, concerns have been raised as to whether finasteride use increases the risk of male breast cancer. Previous epidemiologic evidence on the potential link is conflicting. This study aimed to assess whether an association between finasteride use and male breast cancer exists after accounting for potential confounders.

The source population consisted of all men (≥35 years) from Denmark (1995–2014), Finland (1997–2013), and Sweden (2005–2014). Cases with incident male breast cancer were identified in the cancer registries and matched with 50 density-sampled, age, and country-matched male population controls per case. Exposure information on finasteride use was derived from the prescription registries. Potential confounders were identified using the directed acyclic graph methodology and measured by use of information from nation-wide registries.

The study population comprised 1,005 male breast cancer cases and 43,058 controls. Confounder-adjusted odds of finasteride exposure were not statistically significantly increased [OR, 1.09; 95% confidence interval (CI), 0.77–1.54] in breast cancer cases relative to controls. There was no evidence of a dose–response relationship, as the group with greatest exposure to finasteride was associated with lowest OR of male breast cancer [OR, 0.72 (95% CI, 0.40–1.30)]. Sensitivity analyses did not reveal marked changes in results with different exposure definitions or for specific subgroups.

Results from this study provided no evidence that finasteride use was associated with male breast cancer.

This large confounder-adjusted study supports the view that exposure to finasteride is not associated materially with male breast cancer risk.

Finasteride is a type II 5-alpha-reductace inhibitor (5-ARI) blocking the conversion of testosterone to the more potent androgen dihydrotestosterone. Dihydrotestosterone is the primary androgen of the prostate and hair follicles contributing to the development of benign prostatic hyperplasia (BPH) and androgenetic alopecia ( 1 ). Finasteride was approved in the dose of 5 mg for treatment of symptomatic BPH in 1992 and in the 1 mg dose for treatment of androgenetic alopecia in 1997 by the FDA ( 2, 3 ). Finasteride 5 mg was approved in March 1993 in Denmark, June 1992 in Finland, and September 1992 in Sweden. Finasteride 1 mg was approved in November 1998 in Denmark and Finland and April 1998 in Sweden. BPH can cause lower urinary tract symptoms (LUTS) when the enlarged prostate compresses the urethra ( 4 ). BPH is a common condition increasing with age with approximately 50% of men having BPH at age 50 and more than 80% having BPH at age 80 or older ( 5 ). Androgenetic alopecia or male pattern hair loss is a condition influenced by a combination of hereditary and hormone factors ( 6 ). The condition becomes a medical issue if causing distress and affecting quality of life ( 7 ).

Male breast cancer is a rare disease accounting for 0.6% of all breast cancers ( 8 ). The disease has an incidence rate from 1995 to 2014 of 0.5 case per 100,000 person-years in the Nordic countries (age-standardized to the World Standard Population; ref. 9 ). Case reports have raised concerns about a potential link between finasteride use and the development of male breast cancer. In 2009, the Medicines and Healthcare Regulatory Agency summarized in a review that 50 cases of male breast cancer have been reported worldwide in association with finasteride 5 mg and three cases in association with finasteride 1 mg ( 10 ). In the following years, epidemiologic studies have investigated the potential association between finasteride and male breast cancer; however, results from these studies have been affected by small or selected samples, inadequate confounder adjustment, and have shown conflicting results ( 11–15 ).

The rareness of male breast cancer disease makes it difficult to study and requires large study populations to obtain sufficient statistical power. None of the previous studies from the United States, United Kingdom, and Sweden found evidence for an increased risk of male breast cancer among finasteride users or users of any 5-ARI (i.e., finasteride or dutasteride) compared with nonusers ( 11–13, 15 ). The largest study to date, a cross-national Nordic cohort study ( 14 ), was based on approximately the same registry data as the current study, but with a shorter study period, different exclusion criteria, and only adjusting for calendar year, country, and age. This study found an increased incidence rate ratio for male breast cancer comparing finasteride users to nonusers of 1.44 [95% confidence interval (95% CI) = 1.11–1.88; ref. 14 ]. The authors stress that the reported higher incidence might be influenced by unmeasured confounding or surveillance bias, that is, finasteride users being more closely followed by physicians than nonusers, increasing their likelihood for having a breast cancer detected and diagnosed.

The Nordic countries have a long history of establishing and maintaining population registries including registries on cancer, hospital contacts, prescription redemption, and sociodemographic characteristics of the entire population ( 16–19 ). These data make it feasible to examine the association between finasteride and male breast cancer accounting for potential confounders by pooling data at the individual level from more than one country. This study aims to evaluate whether finasteride increases the risk of male breast cancer after accounting for potential confounding factors using cross-national registry data from Denmark, Finland, and Sweden.

Data sources

Individual-level data from Denmark, Finland, and Sweden were collected from nationwide registries by a national coordinator and transferred to Statistics Denmark, where a common database with individual-level records was established. Data were collected from the cancer registries, prescription registries, national patient registries covering all contacts with the hospital (outpatient and inpatient), civil registration systems, and social registries. Individual-level linkage between registries was possible due to the unique personal identity code assigned to all residents at birth or immigration ( 16, 18, 20 ). Data were collected for the period in each country where information from all registries was available. The study period was therefore 1 January 1995 to 31 December 2014 for Denmark, 1 January 1997 to 31 December 2013 in Finland, and 1 July 2005 to December 2014 in Sweden, respectively.

Study design

This study is being performed as a postauthorization safety study commitment to the European Union health authorities. A case–control design was used comparing finasteride redemptions among male breast cancer cases aged 35 years or older with a random sample of age and country-matched controls.

Male breast cancer cases were identified in the three cancer registries as men with first-ever breast cancer. However, male breast cancer patients with previous nonmelanoma skin cancer were included. Breast cancer cases were identified by the International Classification of Disease seventh revision (ICD-7) code 170 or ICD-O-3 code C50. The cancer registries in the Nordic countries are harmonized and characterized by high validity of diagnoses ( 17 ). Cases with previous radical prostatectomy (i.e., treatment for prostate cancer) were excluded to manage the unlikely situation that some of the prostate cancers were missing in the cancer registries. A new users design was applied by excluding cases with finasteride or dutasteride prescription redemptions in the first 6 month of registration in the prescription registries ( 21 ).

Density-sampling was used to sample 50 control men per case alive on the date as the respective male breast cancer diagnosis (index date). In Finland, controls were in addition matched by municipality of residence. Less than 50 controls were sampled for cases where fewer controls were eligible for sampling (especially among the oldest cases). Controls with cancer diagnosed before the index date, except for nonmelanoma skin cancer, were excluded. Same exclusion criteria were performed for controls as for cases, that is, previous radical prostatectomy and use of a new user design.

Information on finasteride use was obtained from the prescription registries by use of the Anatomic Therapeutic Chemical (ATC) code G04CB01 (finasteride 5 mg) and D11AX10 (finasteride 1 mg). All drug purchases of prescription drugs are registered at the individual-level with information on date of purchase, ATC code, number of packages, and number of pills per package. Cumulative finasteride use was calculated by converting all finasteride prescription redemptions into 5 mg packs of 98 pills. In Finland, however, only reimbursed drugs are included in the registry meaning that information on drug purchases of nonreimbursed finasteride 1 mg was unavailable for the Finnish population ( 16 ). In addition, finasteride 5 mg was coded by ATC code G04CB04 in Finland from 1994 to 1996 and was not included in the prescription registry. Consequently, Finland was included in the study from 1997 onwards. In the main analysis, the exposed group was defined as men with at least two prescription redemptions of finasteride compared with unexposed men with none or only one finasteride prescription redemption.

Confounder selection and definition

Potential confounders for the association between finasteride use and male breast cancer were identified at an expert meeting and in the literature ( 22, 23 ). The directed acyclic graph (DAG) method was used to select the minimum set of potential confounders to adjust for and thereby minimize bias when estimating the effect of finasteride on male breast cancer (see the DAG in appendix Fig. S1; ref. 24 ). The potential confounders in the adjustment set were: age at the index date, country, benign prostatic hyperplasia, exogenous testosterone, estrogen therapy, Klinefelter syndrome, educational level, testicular disorders, and urbanization. Klinefelter syndrome and testicular disorder were defined as one or more diagnoses registered in the national patient registries before the index date and BPH as any diagnosis or BPH surgery registered before the index date. Estrogen therapy and exogenous testosterone were defined as having at least two prescription redemptions of the drugs before the index date. Educational level and urbanization were defined as the highest educational achievement (elementary: ≤9 years, short: 10–12 years, medium/long: >12 years) and living in an urban area, respectively. In Denmark and Sweden, information on educational level and urbanization was derived for the year before the index date and if this information was missing then the same year as the index date. In Finland, information on urbanization was obtained in the same way, but information on educational level came from the latest available census (1995, 2000, 2005, or 2010). The ATC and ICD coding of all variables derived from the registries is presented in Supplementary Material Table S1.

Statistical analysis

The confounder-adjusted analysis of the association between finasteride and male breast cancer was performed by use of a conditional logistic regression model. Men with dutasteride use before the index date were excluded from the analyses, as dutasteride is a drug with same indication as finasteride and the purpose of the study was to examine the effect of finasteride exclusively (except for the sensitivity analysis including dutasteride users). It is unclear whether finasteride should be considered a drug that contributes to the development of cancer in the first initial phase or a cancer promoter that influences the late critical period in the carcinogenesis. Consequently, a lag period between finasteride use and diagnosis of cancer was not applied in the main analysis. In addition to the main analysis, sensitivity analyses were performed to examine the robustness of the results when changing the exposure definition or restricting the study population. The sensitivity analyses included defining finasteride by cumulative use based on number of packages purchased (2–3 packs, 4–6 packs, or 7+ packs of 98 pills finasteride 5 mg versus less than two packs of finasteride); including only prescription redemptions of finasteride 5 mg; including persons who have only redeemed finasteride once in the exposed group; and grouping finasteride use into 0, 1, and 2 or more prescription redemptions. Moreover, the subgroup sensitivity analyses included adding persons with previous dutasteride use and combining exposure of finasteride and dutasteride altogether; restricting the study population to age of 65 years and above; only including Denmark and Finland (countries with longest follow up); requiring a 2-year lag period between finasteride use and cancer diagnosis; analyzing data without applying a new user design (i.e., including data on finasteride use in the first 6 months of registration); and stratifying the analysis by surveillance factors (persons with number of prescription redemptions and hospital contact below and above the mean as well as stratifying by cancer stage).

Finally, a random effect meta-analysis summarizing the evidence from four previous studies examining finasteride/5-ARIs and male breast cancer ( 11–15 ) together with this study was performed by use of Review Manager software version 5.3 ( 25 ). The meta-analysis was not initially included in the study protocol, but performed ad hoc to summarize the existing evidence on the association between finasteride and male breast cancer including results from this study. Studies included in the meta-analysis did include finasteride as the exposure (alone or together with dutasteride) and had male breast cancer as the outcome. The studies may differ in the study design, definition of the study population, and the exposure assessment. The study by Mejier and colleagues (2018; ref. 14 ) was not included in the meta-analysis because it was based on data with overlapping time period and study population as to the current study. The DAG was developed by use of DAGitty software version 2.3 ( 26 ). The remaining data management and analyses were performed by use of SAS software version 9.4.

Ethical considerations

According to the law in Denmark, Finland, and Sweden, registry-based studies can be performed without consent from the subjects if the data processing takes place with the only purpose of performing statistical or scientific studies of significant public health concerns and where the processing is required to perform these studies. Before data collection, data management, and data analyses, approval was obtained from the relevant national data agencies required in the three countries.

In total 445, 255, and 328 incident male breast cancer cases were identified in Denmark, Finland, and Sweden and were matched with 22,233, 11,552, and 15,864 controls, respectively ( Fig. 1 ). Controls with cancer before the index date (4,843), controls and cases with previous radical prostatectomy (1 case; 43 controls), or finasteride prescription redemptions in the first 6 months of registration (18 cases; 1,214 controls) were excluded. Cases and controls with previous dutasteride use were excluded from the main analyses (4 cases; 491 controls) leaving 44,063 men for the analysis (1,005 cases; 43,058 controls).

Figure 1. Overview of the study population. The figure illustrates the construction of the study population in Denmark, Finland, and Sweden and the establishment of a common database for analysis with data from all three countries. MBC, male breast cancer.

Overview of the study population. The figure illustrates the construction of the study population in Denmark, Finland, and Sweden and the establishment of a common database for analysis with data from all three countries. MBC, male breast cancer.

Among male breast cancer cases, 38 (3.8%) were new users of finasteride before the index date compared with 1,258 (2.9%) of controls ( Table 1 ). The distribution of confounding factors was similar for cases and controls, except for a slightly higher proportion of the cases with BPH relative to controls (13.2% of cases vs. 10.0% of controls).

Characteristics of male breast cancer cases and controls with respect to finasteride use and potential confounding factors

NOTE: Figures are numbers and percentages if nothing else is stated.

The OR with corresponding 95% confidence interval (95% CI) of finasteride use was 1.18 (0.84–1.65) in the crude analysis accounting for age, country of residence, and calendar time ( Table 2 ). The OR (95% CI) attenuated to 1.09 (0.77–1.54) when adjusting for the remaining confounding factors. It was not possible to adjust for Klinefelter syndrome and estrogen therapy due to too few observations in the strata (see Table 1 ). No clear relationship between finasteride use and male breast cancer was found when examining the cumulative finasteride use. Men who had redeemed 4–6 packs of 98 5 mg finasteride pills had the highest odds of male breast cancer compared with nonusers [1.24 (0.58–2.66)]. The OR for the association between finasteride and male breast cancer did not change markedly in analyses that included only 5 mg finasteride [1.09 (0.77–1.54)] or when including persons with only one prescription redemption in the exposed group [1.21 (0.89–1.64)]. In the analysis comparing the groups of users with one and two or more finasteride prescription redemptions with those who did not use finasteride, the group of men with only one prescription redemption had the highest OR [1.64 (0.93–2.89)].

Conditional logistic regression model for the association between finasteride use and male breast cancer

a Matched for age and country.

b Matched for age and country and adjusted for benign prostatic hyperplasia, exogenous testosterone, educational level, testicular disorders, and urban/rural differences. It was not possible to adjust for Klinefelter syndrome and estrogen therapy due to too few observations in the strata.

c Cumulative finasteride use was calculated by converting all finasteride prescription redemptions into 5 mg packs of 98 pills and dividing the cumulative use into four categories [i.e., nonuse (<2 packs), 2–3 packs, 4–6 packs, and 7+ packs].

Combining finasteride and dutasteride use [0.95 (0.68–1.32)], restricting the analyses to men aged 65 or above [1.02 (0.70–1.48)], inferring a 2-year lag period [0.88 (0.56–1.37)], including only those data from Denmark and Finland with the longest follow-up period [1.20 (0.81–1.78)], or not applying a new user design [1.15 (0.86–1.55)] did not change the results materially ( Table 3 ).

Sensitivity analyses with restriction, stratification, alternative definition of the study population, and surveillance factors

a Matched by age and country. Conditional logistic regression.

b Matched by age and country and adjusted for benign prostatic hyperplasia, exogenous testosterone, educational level, testicular disorders, and urban/rural differences. Conditional logistic regression.

c 104 cases (10.4%) had no information on cancer stage and were therefore excluded from this analysis as were their corresponding 4,430 controls.

The OR of exposure to finasteride was similar when restricting the analysis to men with frequent contact to the healthcare system (i.e., men with number of hospital contact and prescription redemptions above the mean [0.94 (0.63–1.41) and 1.03 (0.71–1.51), respectively]. Likewise, the ORs did not vary markedly between breast cancers of localized versus nonlocalized stage ( Table 3 ).

The meta-analysis included the four previous studies examining finasteride/5-ARIs and male breast cancer ( 11–15 ) together with this study. The meta-analysis showed no evidence of heterogeneity ( P = 0.48) among the five studies included ( Fig. 2 ). The pooled relative risk estimate (95% CI) for the association between finasteride/5-ARI and male breast cancer was 1.00 (0.78–1.27).

Figure 2. Meta-analysis of the studies on finasteride/5-ARI and male breast cancer, including four previous studies and this study. The individual studies included in the meta-analysis are illustrated by squares, with the size of the square symbolizing the size of the study, and the 95% confidence intervals (CI) are illustrated by the width of the line. The pooled estimate is shown by a black diamond, with the width of the diamond illustrating the 95% CI.

Meta-analysis of the studies on finasteride/5-ARI and male breast cancer, including four previous studies and this study. The individual studies included in the meta-analysis are illustrated by squares, with the size of the square symbolizing the size of the study, and the 95% confidence intervals (CI) are illustrated by the width of the line. The pooled estimate is shown by a black diamond, with the width of the diamond illustrating the 95% CI.

No significantly increased odds of exposure to finasteride were found for male breast cancer cases relative to controls. The OR for the association between finasteride use and male breast cancer decreased when accounting for potential confounders. In the protocol of this study, confounding was assumed to be an important bias of the association between finasteride and male breast cancer; however, the actual results did not support that confounding did influence the results markedly although the estimates attenuated slightly. Changes in the definition of finasteride use or performing restrictions of the study population did not change the results materially. No increased OR for the association between finasteride and male breast cancer was seen among men who were often in contact with the healthcare system and therefore more likely to undergo disease surveillance.

Results from this study contribute to the existing epidemiologic evidence on the association between finasteride and male breast cancer in supporting no evidence for a raised risk, and if there is any raised risk it is likely to be small or modest. The first epidemiologic study from the United States found no evidence of an association between 5-ARIs and male breast cancer with an OR (95% CI) of exposure in one or more years of 0.70 (0.34–1.45 ref. 11 ). Likewise, Duijnhoven and colleagues (2014) found no evidence that men treated with 5-ARIs had an increased risk of male breast cancer with an OR (95% CI) of 1.08 (0.62–1.87). In addition, no association between 5-ARI and male breast cancer was observed in two smaller studies from United Kingdom and Sweden, respectively ( 13, 15 ). A cross-national study by Mejier and colleagues (2018) was based on data from the Nordic countries in line with this study and found a statistically significant increased incidence rate of male breast cancer among finasteride users compared with nonusers [IRR (95% CI) = 1.44 (1.11–1.88); ref. 14 ]. Some differences in study population and design exist between these two Nordic studies, which explain the lower risk estimate found in this study relative to the previous Nordic study (i.e., different follow-up period, exclusion criteria, confounder adjustment, exposure definition, and Norway included in the earlier study). When analyzing data from this study to mirror the analysis of Meijer and colleagues (2018) with a shorter study period, no exclusion criteria and including men with only one prescription redemption of finasteride in the exposed group, the estimate of the association between finasteride and male breast cancer was 1.60 (1.18–2.17). It was not possible to study the effect of including Norway as Norwegian data were not available in this study. However, as only one male breast cancer case from Norway was exposed to finasteride in the Meijer and colleagues (2018) study, we do not expect the difference between the two studies to be explained by the exclusion of Norwegian data. This study is likely to provide a more valid estimate of the association between finasteride use and male breast cancer than Meijer and colleagues (2018) as a more advanced study design was applied incorporating a new user design, including longer follow-up period (important if the latency period is long) and not including men with only one prescription redemption as exposed as these men are likely not to have consumed the drug or only used it for a very short time.

The study was performed as a response to a drug safety concern regarding a potential signal of increased risk of male breast cancer, a serious but rare disease, meaning that the width of the confidence interval is important to consider. However, given the low age-adjusted incidence rate of breast cancer among men in the Nordic countries from 1995 to 2014 of about 0.5 cases per 100,000 person years ( 9 ), even an OR or RR close to the upper limit of the 95% confidence interval (i.e., 1.54 in this study and 1.27 in the pooled meta-analysis) results in a small absolute number of male breast cancer cases attributable to finasteride.

Strengths of the study include the advantage of merging nationwide individual-level data across countries providing a source population of the entire male population aged 35 years or older from three countries. Hence, the study population was representative of adult men in the Nordic countries increasing the generalizability of the results to other populations outside the Nordic countries especially other populations mainly consisting of Caucasian men. Moreover, a merit was the large number of men exposed to finasteride. A previous study reported a period prevalence of finasteride use among men aged 15 years and older to range from 4.9 users/1,000 men in Denmark to 18.2 users/1,000 men in Finland ( 27 ). Because of the long history of the population registries in the Nordic countries, another merit of this study was the long follow-up of finasteride users making it possible to study a rare disease with potentially long latency period as is the case with male breast cancer. Another strength of the study is that the prescription registers cover close to all prescription drugs except for drugs handled out in the hospitals and online drugs purchased from other countries. In Denmark, more than 99% of finasteride is purchased at pharmacies outside the hospitals and this proportion is assumed to be similar in Finland and Sweden ( 28 ). No subsidies are given for prescription drugs purchased via the internet from other countries and it is therefore unlikely to be used often for subsidized drugs as there is no economic benefit for the purchaser. Finally, the high validity of cancer diagnoses in the Nordic cancer registries and the harmonization of the cancer and prescription registries of the Nordic countries contribute to high internal validity of the results ( 17, 19, 29 ).

A limitation of the study is the unknown drug compliance, as finasteride exposure is based on dispensed and not necessarily consumed drugs. However, this potential overestimation of the exposure was compensated by including only persons with at least two prescription redemptions in the exposed group increasing the likelihood that the drug was actually consumed. It was not feasible to adjust for the potential confounders Klinefelter syndrome and estrogen therapy, as too few men had the diagnosis or had received the treatment. As an alternative strategy, a restriction of the analysis was performed by excluding men with Klinefelter syndrome or estrogen therapy ( n = 14, only controls) and this did not change the results. Even though this study is the largest to date with 1,005 cases, a limitation of the study is that only 38 cases were exposed to finasteride.

In conclusion, no evidence of an association between finasteride and male breast cancer was found in this large and confounder-adjusted cross-national registry-based study with a long follow-up period.

A. Green and M. Emneus served as consultants for Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., in connection with the study presented in this paper. No potential conflicts were disclosed by the other authors.

Conception and design: T.M. Kjærulff, A.K. Ersbøll, A. Green, M. Emneus, K. Brasso, P. Iversen, E. Pukkala, L.C. Thygesen

Development of methodology: T.M. Kjærulff, A. Green, K. Brasso, P. Iversen, E. Pukkala, L.C. Thygesen

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): T.M. Kjærulff, A. Green, M. Emneus, K. Brasso, E. Pukkala, K. Bolin, L.C. Thygesen

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): T.M. Kjærulff, A.K. Ersbøll, A. Green, K. Brasso, P. Iversen, E. Pukkala, K. Bolin, L.C. Thygesen

Writing, review, and/or revision of the manuscript: T.M. Kjærulff, A.K. Ersbøll, A. Green, K. Brasso, P. Iversen, E. Pukkala, K. Bolin, L.C. Thygesen

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): T.M. Kjærulff, M. Emneus, L.C. Thygesen

Study supervision: A.K. Ersbøll, M. Emneus

This article is based on data originating from a study conducted by Applied Economics and Health Research (ApEHR) as an independent research institute/organization based on a regulatory request from the European Medicines Agency (EMA) and funded by Merck Sharp & Dohme Corp (MSD). The included ad hoc meta-analysis on the association between finasteride and male breast cancer was not included in the initial protocol and was not covered by the funding from MSD. MSD has had the opportunity to comment on the manuscript, but the authors retained the right to accept or reject comments or suggestions.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supplementary data

Anatomic Therapeutic Chemical (ATC) and International Classification of Disease (ICD) codes used for male breast cancer, finasteride and potential confounders used in the three countries

Final directed acyclic graph (DAG) of the association between finasteride and male breast cancer

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  • Published: 17 May 2022

Infertility and risk of breast cancer in men: a national case–control study in England and Wales

  • Anthony J. Swerdlow   ORCID: orcid.org/0000-0001-5550-4159 1 , 2 ,
  • Cydney Bruce 1 , 3 ,
  • Rosie Cooke 1 , 4 ,
  • Penny Coulson 1 &
  • Michael E. Jones 1  

Breast Cancer Research volume  24 , Article number:  29 ( 2022 ) Cite this article

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Breast cancer is uncommon in men and its aetiology is largely unknown, reflecting the limited size of studies thus far conducted. In general, number of children fathered has been found a risk factor inconsistently, and infertility not. We therefore investigated in a case–control study, the relation of risk of breast cancer in men to infertility and number of children.

Patients and methods

We conducted a national case–control study in England and Wales, interviewing 1998 cases incident 2005–17 and 1597 male controls, which included questions on infertility and offspring.

Risk of breast cancer was statistically significantly associated with male-origin infertility (OR = 2.03 (95% confidence interval (CI) 1.18–3.49)) but not if a couple’s infertility had been diagnosed as of origin from the female partner (OR = 0.86 (0.51–1.45)). Risk was statistically significantly raised for men who had not fathered any children (OR = 1.50 (95% CI 1.21–1.86)) compared with men who were fathers. These associations were statistically significantly present for invasive tumours but not statistically significant for in situ tumours.

Our data give strong evidence that risk of breast cancer is increased for men who are infertile. The reason is not clear and needs investigation.

Introduction

Breast cancer is comparatively rare in men, and its aetiology is largely unknown. There are several commonalities with the disease in women, including a genetic component with several specific genes and SNPs known [ 1 ] and a relation to anthropometric factors [ 2 ]. There is a very high risk in men with Klinefelter syndrome [ 3 ], and this, along with the relation to anthropometrics, suggests that sex hormone-related factors might be involved, as they are in women, and a raised risk of breast cancer has been found in the only cohort analysis able to examine prior oestradiol levels in men who subsequently developed breast cancer [ 4 ]. In women, reproductive-related factors are important in breast cancer aetiology [ 5 ], notably a reduced risk in parous women, and although that relates to the hormonal consequences of parity, which could not plausibly apply in men, it nevertheless seems worth investigating whether male fertility relates to male breast cancer risk. Klinefelter syndrome is associated with infertility [ 6 ], and there is some, but not definitive, evidence that testicular abnormalities may also be associated with male breast cancer risk [ 2 ]. Infertility is generally defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourse and can be of male origin or female or contributions from both [ 7 ].

Investigation of the relation of male infertility and reproductive history to breast cancer risk has been hampered, however, by the rarity of the tumour. Few studies have investigated infertility [ 8 , 9 , 10 ] or reproductive history [ 2 , 11 , 12 , 13 , 14 , 15 ], the largest based on 227 cases of whom 7 reported male infertility [ 8 ]. A pooled analysis has been published [ 2 ], but is difficult to interpret because the small studies aggregated had very varied case and control selection criteria, and varied also in definitions of infertility. No significant relation to infertility was found, but there was a significant relation to whether the subject had any children. We have conducted a case–control study in England and Wales covering almost 2000 cases nationally incident over a 12.7 year period and present here the results relating to fertility and children.

Materials and methods

The study is of case–control design, with potential cases being all male residents of England and Wales with in situ or invasive breast cancer diagnosed in these countries at ages < 80 years during 1 January 2005 to 31 August 2017. These cases were identified from clinician reports to us and comprehensive listings from national population-based cancer registries.

Since attempts to recruit population-based controls now give very low and selective recruitment rates [ 16 , 17 ], we recruited controls nationally from two sources for which compliance was much higher and made comparisons between the two sources to assess potential bias. The first source was male non-blood relatives of the cases, ascertained by asking the cases about such relatives and then selecting one or more on the basis of stratum-matching on age and geographic region. Secondly, we recruited as controls the husbands of women participating in the Generations cohort study [ 18 ], again stratum-matched to cases, and approached via their wives. Since for all of the analyses in the current paper, the two control groups gave results in the same direction, we present in this paper the results for the two groups of controls combined.

Potential cases and controls were asked if they would take part in the study, and if so were interviewed, usually in their homes, by trained research nurse interviewers using a structured questionnaire. The nurses also took a blood sample (or if not possible, a saliva sample) for genetic analyses. The questionnaire enquired about demographic factors and potential risk factors for breast cancer including infertility and offspring. For infertility, we asked whether the subject or their partner had “ever had problems trying to have children for which you or she went to a doctor or infertility clinic’’ and if so we asked for the outcome of the consultation, with responses recorded according to which partner(s) were stated to be the cause of the infertility, and if the case was stated to be infertile, what treatment if any they had received. For offspring, we asked about each biological child the man had fathered, including any who had died.

Analyses of the study data were by standard methods for case–control studies [ 19 ], calculating odds ratios (as estimates of relative risks) adjusted for ‘index’ age, year of interview, socio-economic status (residential-based ‘Acorn’ score) [ 20 ], marital status and region of residence. The index age for cases was the age at diagnosis, and for controls was an equivalent age derived by calculating for each calendar year of interview, the mean duration for cases from cancer diagnosis to interview, and then subtracting this duration from the age at interview of each control interviewed in that calendar year. Linear trends in risk by exposure level were analysed as continuous variables [ 19 ]. We took p  < 0.05 in a two-sided test to indicate statistical significance.

To examine misclassification and potential confounding, we conducted several sensitivity analyses: excluding subjects whose quality of responses to the overall questionnaires were rated by the interviewer as ‘not well’ or ‘very poorly’; excluding subjects with Klinefelter syndrome, and then excluding also those with other factors that are potential confounders, namely certain testicular conditions, severe obesity, and previous primary cancers that might have involved chest radiotherapy and that directly or via their treatments might have affected fertility; and analyses restricted to married men, as an alternative to adjustment for marital status, since one of the two control groups (the ‘Generations Study’ controls) was by consequence of its source married. We also conducted sensitivity analyses adjusting additionally for alcohol consumption, smoking, family history of breast cancer, and liver disease, in case these might be confounders, although there is no strong evidence that they are.

From the cancer registries and consultant notifications, we identified 3187 men resident in England and Wales diagnosed during the study period with breast cancer at ages under 80 years. Of these, 433 died (427) or emigrated (6) before we could make contact with them, for 21 we could not identify the consultant or the consultant did not participate, for 28 the consultant deemed the patient unsuitable to be approached, and 707 did not reply to our invitation or declined to participate. The remaining 1998 (62.7%) were interviewed. They were mainly (Table 1 ) aged 60 years or older at diagnosis, and the tumours were mostly invasive (92.0%) rather than in situ (8.0%), and largely oestrogen receptor positive (98.5% of those with known status). Cases tended to be older than controls, of higher socio-economic status, less often married, less often from the south of England, and interviewed more recently (Table 1 ): all of these relations except region were statistically significant, and these factors were adjusted for in the risk analyses.

We approached 828 men to be non-blood relative controls, of whom 613 (74.0%) participated, and we approached 1,109 potential Generations Study controls, of whom 984 (88.7%) participated.

One hundred and twelve (5.6%) cases and 80 (5.0%) controls reported that they had had infertility problems for which they or their partner had consulted a doctor or infertility clinic (Table 2 ). The prevalence of infertility did not vary by age (controls P  = 0.90; cases P  = 0.39). The odds ratio for ever-infertility was statistically non-significantly raised (OR = 1.29, 95% confidence interval (CI) 0.94–1.77). When analysed by outcome of the infertility consultation, there was a statistically significantly raised risk for men who said that they were diagnosed as the source of the couple’s infertility (OR = 2.03 (1.18–3.49)), but not for those whose partner was the source of the infertility (OR = 0.86 (0.51–1.45)) or for whom no source was identified (OR = 1.26 (0.71–2.24)). The same pattern was true in analyses excluding men with Klinefelter syndrome (infertility OR = 1.23 (0.89–1.69); self as source of infertility (OR = 1.81 (1.02–3.20)) and in analyses also excluding men with potentially confounding conditions (Table 2 ). Analyses restricted to married men were based on somewhat smaller numbers (1600 cases, 1539 controls), but showed similar results, with a statistically significant risk ( p  = 0.02) for men who were themselves infertile (not in Table). Risk was also statistically significantly raised if we aggregated men who were either diagnosed as the source or said the source was unknown but they had been diagnosed with a low sperm count (OR = 2.17 (1.29–3.67), P  = 0.004, not in table).

One thousand, six hundred and fifteen (80.8%) cases and 1423 (89.1%) controls had fathered any children (Table 3 ). There was a statistically significantly raised risk (OR = 1.50 (1.21–1.86), p  < 0.001) for childless men. Analysis by number of children showed a highly statistically significant inverse trend if zero was included as a value ( p  < 0.001) but a borderline statistically significant trend if it was not ( p  = 0.04). These results remained statistically significant when men with Klinefelter syndrome were excluded (not in table), when in addition potentially confounding conditions were excluded (Table 3 ), and when analyses were restricted to married men (for childless men p  < 0.001; not in Table). There was no relation of risk to age of the men at birth of their first child (Table 4 ). When infertility and number of children were fitted together (not in Table), the trend with number of children was inverse ( P  = 0.04) and the OR for men who reported that they were diagnosed as the source of infertility was less raised (OR = 1.68 (0.96–2.93)), and there were modest changes for men whose partner was the source of infertility (OR = 0.76 (0.45–1.29)) or for whom no source was identified (OR = 1.12 (0.63–2.01)).

Sensitivity analyses excluding men whom the interviewers considered to be relatively unreliable gave similar results to those above, and in particular risks for men who were themselves the cause of the couple’s infertility ( p  = 0.04), and for men with no children ( p  < 0.001), remained statistically significantly raised (not in Table). Sensitivity analyses adjusting additionally for alcohol consumption, smoking, liver disease and family history of breast cancer (see Methods) did not change the results materially (not in Table).

In analyses separately for invasive ( n  = 1838) and in situ ( n  = 160) tumours (Table 5 ), the relations above were present and statistically significant for the former (unsurprisingly since they were > 90% of the total), but odds ratios were generally closer to 1.0, and in no instance statistically significant, based on much smaller numbers, for the latter. There were too few tumours that were ER-ve to conduct analyses by ER status (Table 1 ), but results for HER-2 + ve ( n  = 187) and − ve ( n  = 1376) tumours separately each gave similar results, with statistically significantly raised risks for male infertility ( p  = 0.04 and 0.01, respectively) and for having no children ( p  = 0.01 and < 0.001, respectively) (not in Table).

Our large case–control study has shown a clear, statistically significant, association between reported diagnosis of male infertility and risk of breast cancer, and this was supported by analysis of numbers of offspring—there were significantly more men with no children among cases than among controls, both overall and after excluding potentially confounding conditions, and in analyses restricted to married men.

Case–control studies are notoriously at risk of bias, but there seems no plausible reason why our infertility results should have been artefactual. Although our controls, unlike the cases, were not strictly population-based, because of the poor response rate now for population-based controls [ 16 , 17 ], they were drawn from the whole country and age range of the cases, we adjusted for the difference in distribution of relevant variables between the cases and controls, and the infertility results were present in comparisons with each of the two control groups, from different sources, used in the study. The association with infertility is not one plausibly known to the subjects, and there is no obvious reason why the men should have recalled or reported it in a way biased between cases and controls, especially for reporting of number of children. We could not interview patients who died before they could be approached or interviewed, which could lead to bias if survival was related to infertility, but there is no obvious reason why it should be nor any evidence for such an association to our knowledge. Although a small part of the association is explicable by the known association of male breast cancer with Klinefelter syndrome [ 21 ], this is far too rare to account for the overall relation, which persisted after excluding subjects with known Klinefelter, based on cytogenetic karyotyping of the first 901 cases and self-reporting of diagnosis for the remainder. The association also largely remained after additional exclusion of patients with other pre-existing potential confounders, namely severe obesity, past malignancies that can be treated with chest radiotherapy, and testicular abnormalities [ 22 ]. It is arguable, however, whether the latter exclusions are overly conservative, since several of the testicular conditions, which were the main exclusions, may have been diagnosed as a consequence of investigations for infertility rather than diagnosed independently of it: we did not have information to determine the sequence of diagnostic dates. There are several other factors that are known or posited to be related to risk of infertility, including diabetes, dyslipidaemia, cirrhosis of the liver, alcohol consumption, smoking, and endocrine disrupting chemicals [ 7 ], but there is no convincing evidence that these factors are related to risk of breast cancer in men [ 2 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 23 ], and hence, no reason to believe that they are confounders for which adjustment would be needed in our infertility analyses. Conversely, known risk factors for breast cancer in men, family history of breast cancer and risk genotypes [ 1 ] are not known to be associated with risk of infertility and hence again are not clear confounders. Nevertheless, in sensitivity analyses, adjustment for those of these variables for which we had data made no material difference to the results.

Self-reported fertility is a ‘soft’ measure with potential for misclassification for several reasons. Infertility is a complex process that can include factors from both the male and female members of a couple; men may not report (or even know of) children born outside marriage; they may have remained childless by choice, not infertility; and they may report a low sperm count even if it was not the reason for infertility. Additionally, the self-reports were reliant on the men’s recall and understanding—the evidence would have been stronger if infertility could have been validated from medical records, but this was not practical across an entire country over many decades. However, although all of the above sources of misclassification might plausibly have led to dilution and hence underestimation of any true risks, there is, as noted above, no obvious reason why this should have been differential between cases and controls, and hence have led to bias.

The lack of a significant association of male breast cancer with infertility in most of the previous literature does not argue substantially against the association that we found: the few published studies [ 8 , 9 , 10 ] have had mixed results, with at most only 227 cases of whom 7 reported infertility [ 8 ]. A pooled analysis that included 420 cases [ 2 ] found a non-significant odds ratio of 1.36, although based on heterogeneous case–control studies with heterogeneous definitions of infertility that complicate interpretation, and with analysis solely of a dichotomy between “history of infertility” and no such history.

Our finding of greater risk for men with no biological children compared with any children is congruent with infertility as a risk factor. Most previous studies have not found such an effect, but based on very small numbers [ 11 , 12 , 15 , 24 ], although one small study [ 13 ] (21 cases) and a pooled analysis [ 2 ] found significantly raised risk for men with no children.

We found significantly decreasing risk with increasing numbers of children. However number of children beyond one is difficult to interpret as an indicator of male fertility, since it may more reflect social and cultural factors than fertility per se. The same is true for age at first birth. Similarly, it is difficult to interpret analyses confined to married men because of the changing relation of marital status to fatherhood in Britain, such that the meaning of ‘married’ in relation to potential for fatherhood has changed over time. Before 1980, 10% or fewer of births in England and Wales were outside marriage, but the proportion has since soared such that by 2000, 40% were outside marriage and subsequently almost 50% [ 25 ]. In our main analyses, we adjusted for marital status; in comparison, analyses confined to married men showed slightly less marked odds ratios, but entirely in the same direction.

Our data showed that the association of infertility with male breast cancer risk was clearly present for invasive tumours, but not significant, based on much smaller numbers, for in situ tumours: this does not appear to have been investigated previously.

The reason for the association of male infertility with breast cancer risk demonstrated in our data is uncertain. Infertility can result from a wide range of factors, including genetic, congenital anomalies of the genitourinary tract, other anatomical reasons, and sexual dysfunction, but most cases are idiopathic [ 22 ].

The main source of testosterone secretion in men is the testis, so one potential link between infertility and breast cancer risk would be via hormonal effects of testicular abnormalities. For instance, mumps orchitis can lead to testicular atrophy and long-term reduced testosterone production [ 26 ], and can lead, albeit not commonly, to subfertility or, rarely, sterility [ 27 ]. Although significant associations remained (albeit slightly reduced) after exclusion of men diagnosed with testicular abnormalities that have been reported to be associated with breast cancer risk, it is possible that associations remained from other abnormalities of the testes not know to be risk factors, or more subtle abnormalities that would not receive a diagnosis.

It has been hypothesised that prenatal oestrogen exposure can lead to raised risk of male infertility [ 28 ], in which case a possible connection would be if the prenatal hormone environment might also affect male breast cancer risk, as hypothesised for women [ 29 ].

Conclusions

In summary, our large case–control study gives strong evidence that male infertility is associated with raised risk of breast cancer in men. The reasons are uncertain and need to be investigated.

Availability of data and materials

The statistical output data underlying this article will be shared on reasonable request to the corresponding author. The individual subject data underlying this article cannot be shared because of the privacy of the individuals who participated in the study.

Abbreviations

Confidence interval

Oestrogen receptor

Human epidermal growth factor receptor 2

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Acknowledgements

We thank the men who participated in the study; the cancer registries of England and Wales for providing us with information on eligible participants; and the consultants under whose care the patients were for their advice and help; and our colleagues who coordinated information on controls, who interviewed the patients and who gave administrative help and advice. This work uses data that have been provided by patients and collected by the NHS as part of their care and support. The data are collated, maintained and quality assured by the Welsh Cancer Intelligence and Surveillance Unit and by the National Cancer Registration and Analysis Service, which is part of Public Health England (PHE). Access to the English data was facilitated by the PHE Office for Data Release.

We thank Breast Cancer Now, formerly Breakthrough Breast Cancer, and the John Tridgell family, in memory of John Tridgell, for funding. The ICR acknowledge NHS funding to the NIHR Biomedical Research Centre. The funding bodies had no role in the study design, collection, analysis, interpretation of data and writing of the manuscript.

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Contributions

AJS, RC and MEJ designed the study; AJS, RC and CB organised the data collection; CB, PC, and RC collated the data for analysis; CB and MEJ analysed the data; AJS was the major contributor in writing the manuscript. All authors read and approved the final manuscript.

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Swerdlow, A.J., Bruce, C., Cooke, R. et al. Infertility and risk of breast cancer in men: a national case–control study in England and Wales. Breast Cancer Res 24 , 29 (2022). https://doi.org/10.1186/s13058-022-01517-z

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The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study

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  • Published: 04 February 2024

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  • Hasan Çağrı Yıldırım   ORCID: orcid.org/0000-0003-3060-377X 1 ,
  • Yasin Kutlu 2 ,
  • Emel Mutlu 3 ,
  • Musa Barış Aykan 4 ,
  • Mustafa Korkmaz 5 ,
  • Selim Yalçın 6 ,
  • Teoman Şakalar 7 ,
  • Özde Melisa Celayir 8 ,
  • Erkan Kayıkçıoğlu 9 ,
  • Ferit Aslan 10 ,
  • Emre Hafızoğlu 11 ,
  • Yunus Emre Altıntaş 12 ,
  • Merve Keskinkılıç 13 ,
  • Elvin Chalabiyev 1 ,
  • Abdussamet Çelebi 14 ,
  • Bengü Dursun 15 ,
  • Caner Kapar 16 ,
  • Miraç Özen 17 ,
  • Ömer Acar 18 ,
  • Özgecan Dülgar 19 ,
  • Engin Kut 20 ,
  • Sedat Biter 21 ,
  • Fatih Kus 1 ,
  • Elvina Almuradova 22 ,
  • Atike Pınar Erdoğan 18 ,
  • Seray Saray 23 ,
  • Deniz Can Güven 1 ,
  • Eda Tanrıkulu Şimşek 24 ,
  • Necdet Üskent 24 ,
  • Yasemin Kemal 25 ,
  • Burcu Çakar 26 ,
  • Özgür Açıkgöz 2 ,
  • Saadettin Kılıçkap 27 &
  • Sercan Aksoy 1  

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Introduction

Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 −) breast cancer in women, limited data exist on their effectiveness in male patients.

We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer.

This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects.

A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92–27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70–37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51–37.42) vs 28.33 months (95% CI 14.77–41.88), respectively, p  = 0.211). No new adverse events were reported.

This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 − metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

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Hasan Çağrı Yıldırım, Elvin Chalabiyev, Fatih Kus, Deniz Can Güven & Sercan Aksoy

Department of Medical Oncology, Istanbul Medipol University Medical Faculty, Istanbul, Turkey

Yasin Kutlu & Özgür Açıkgöz

Department of Medical Oncology, Erciyes University Faculty of Medicine, Kayseri, Turkey

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Musa Barış Aykan

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Selim Yalçın

Department of Medical Oncology, Kahramanmaras Necip Fazıl City Hospital, Kahramanmaras, Turkey

Teoman Şakalar

Department of Medical Oncology, MAA Acıbadem University, Istanbul, Turkey

Özde Melisa Celayir

Department of Medical Oncology, Süleyman Demirel University, Isparta, Turkey

Erkan Kayıkçıoğlu

Department of Medical Oncology, Medicalpark Ankara Batıkent Hospital, Ankara, Turkey

Ferit Aslan

Department of Medical Oncology, Ankara City Hospital, Ankara, Turkey

Emre Hafızoğlu

Department of Medical Oncology, Koc University Medical Faculty, Istanbul, Turkey

Yunus Emre Altıntaş

Department of Medical Oncology, Eylül University Faculty of Medicine, İzmir, Turkey

Merve Keskinkılıç

Department of Medical Oncology, Marmara University Faculty of Medicine, Istanbul, Turkey

Abdussamet Çelebi

Department of Medical Oncology, Ankara University Faculty of Medicine, Ankara, Turkey

Bengü Dursun

Department of Medical Oncology, Bakırkoy Dr. Sadi Konuk Educatıon and Research Hospital, Istanbul, Turkey

Caner Kapar

Department of Medical Oncology, Sakarya University Faculty of Medicine, Sakarya, Turkey

Department of Medical Oncology, Manisa Celal Bayar University Faculty of Medicine, Manisa, Turkey

Ömer Acar & Atike Pınar Erdoğan

Department of Medical Oncology, Umraniye Training and Research Hospital, Istanbul, Turkey

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Department of Medical Oncology, Tınaztepe Galen Hospital, Izmir, Turkey

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Department of Medical Oncology, Anadolu Medical Center, Kocaeli, Turkey

Eda Tanrıkulu Şimşek & Necdet Üskent

Department of Medical Oncology, Samsun Medical Park Hospital, Samsun, Turkey

Yasemin Kemal

Department of Medical Oncology, Ege University Faculty of Medicine, İzmir, Turkey

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Yıldırım, H.Ç., Kutlu, Y., Mutlu, E. et al. The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study. Int J Clin Oncol (2024). https://doi.org/10.1007/s10147-023-02460-5

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DOI : https://doi.org/10.1007/s10147-023-02460-5

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Male Breast Cancer Results

Frequently Asked Questions

Evaluation of contaminated drinking water and male breast cancer at Marine Corps Base Camp Lejeune, North Carolina: a case control study

Study Purpose

Some residents who lived at Camp Lejeune from the 1950s through 1985 were exposed to contaminated drinking water.

The purpose of this study was to determine if Marines who were exposed to contaminated drinking water at Camp Lejeune were more likely to have male breast cancer.

Drinking water at Camp Lejeune was contaminated with volatile organic compounds (VOCs), including trichloroethylene (TCE), tetrachloroethylene (PCE), benzene, 1,2-dichloroethylene (DCE), and vinyl chloride.

What Was Studied

The study included 71 men with breast cancer (called “cases”) and 373 men who had other types of cancer (called “controls”). ATSDR used the Department of Veteran’s Affairs (VA) cancer registry to identify these cases and controls. ATSDR selected the controls from cancers that are not associated with solvent exposure; this included 270 men with skin cancer, 71 with mesothelioma, and 32 with bone cancer.

The VA’s cancer registry maintains information from eligible veterans who were diagnosed with or treated for cancer at a VA clinic. Eligible study members were male Marines born before January 1, 1969 and diagnosed with cancer or treated for cancer at a VA medical facility from January 1, 1995, (the start of the VA’s cancer registry) to May 5, 2013 (the latest date that complete medical records were available). Marines born after January 1, 1969 were not old enough to serve during the period of contamination at Camp Lejeune (i.e. they were younger than 17 years of age by the end of 1985 when the contamination ended).

Features of this Study

Because of the lack of existing information, ATSDR used extensive water modeling to reconstruct exposures before 1987. The water modeling identified where and when certain areas at Camp Lejeune received contaminated drinking water. ATSDR used the water modeling results to determine which Marines were exposed to contaminated water during their service.

ATSDR combined the water modeling results with additional information from personnel records, base family housing records, and records that indicated where Marine units were barracked. ATSDR used all of this information to estimate contaminant-specific residential exposure levels for each of the cases and controls in the study who were stationed at Camp Lejeune.

Conclusion and Key Results

ATSDR’s study results suggested possible associations between exposure to PCE, DCE, and vinyl chloride at Camp Lejeune and male breast cancer. These results took into account age at diagnosis, race, and service in Vietnam. For PCE, risk increased slightly with increasing levels of exposure.

Exposures to TCE, PCE, DCE, and vinyl chloride were also observed to possibly accelerate the onset of male breast cancer.

The study did not find evidence suggesting associations between male breast cancer and exposures to benzene.

The results of this study add to the scientific literature on the health effects of exposures to these chemicals in drinking water. However, these findings were based on small numbers of exposed cases.

ATSDR intends to evaluate male breast cancer in a planned cancer incidence study that will involve state cancer registries nationwide as well as federal cancer registries.

  • Journal Article

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Risk factors for male breast cancer--a case-control study from Scandinavia

Affiliation.

  • 1 Danish Cancer Society, Division for Cancer Epidemiology, Copenhagen, Denmark.
  • PMID: 11504305
  • DOI: 10.1080/028418601750288181

We report a population-based case-control study on risk factors for male breast cancer. Data on a broad range of previously suggested risk factors were collected in a set of Scandinavian breast cancer cases and matched controls. Incident cases (n = 282) with histologically verified carcinomas of the breast were identified from notification to the cancer registries of Denmark, Norway and Sweden over a 4-year period 1987-1991 and of these cases, 156 men could be approached and responded. Controls were identified through national central population registers and were matched individually for country, sex and year of birth. Controls with a diagnosis of breast cancer were excluded; 468 of 780 controls responded. Data on risk factors were collected by self-administered questionnaires mailed to the cases between land 2 years after diagnosis and to controls during the same period. The findings were compatible with an increased risk associated with family history of breast cancer (odds ratio (OR) = 3.3, 95% confidence interval (CI) 2.0-5.6), obesity 10 years before diagnosis (OR = 2.1, 95% CI 1.0-4.5) for BMI > 30, diabetes (OR = 2.6, 95% CI 1.3-5.3) and the use of digoxin and methyldopa (OR = 2.0 and 2.1, respectively). The association with family history of breast cancer has been repeated in several studies, while the relation to anthropometric measures has been equivocal. We could not substantiate some associations seen in other studies; namely those with high education, fertility, marital status, testicular injury, liver disease and religion. The detailed questions about gynaecomastia indicated that many cases reported signs of breast cancer as a gynaecomastia. This type of misunderstanding may explain the strong association with gynaecomastia seen in other studies. Several patients died before contact. Thus, risk factors related to a more aggressive male breast cancer or related to high risk of dying (e.g. liver cirrhosis, heavy smoking) may have been missed.

  • Anthropometry
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms, Male / epidemiology*
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  • Case-Control Studies
  • Comorbidity
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  • Gynecomastia / epidemiology
  • Obesity / epidemiology
  • Occupations
  • Precancerous Conditions / epidemiology
  • Prostatic Neoplasms / epidemiology
  • Risk Factors
  • Scandinavian and Nordic Countries / epidemiology

ScienceDaily

Novel technique has potential to transform breast cancer detection

An innovative breast imaging technique provides high sensitivity for detecting cancer while significantly reducing the likelihood of false positive results, according to a study published today in Radiology: Imaging Cancer , a journal of the Radiological Society of North America (RSNA). Researchers said the technique has the potential to offer more reliable breast cancer screening for a broader range of patients.

Mammography is an effective screening tool for early detection of breast cancer, but its sensitivity is reduced in dense breast tissue. This is due to the masking effect of overlying dense fibroglandular tissue. Since almost half of the screening population has dense breasts, many of these patients require additional breast imaging, often with MRI, after mammography.

Low-dose positron emission mammography (PEM) is a novel molecular imaging technique that provides improved diagnostic performance at a radiation dose comparable to that of mammography.

For the study, 25 women, median age 52, recently diagnosed with breast cancer, underwent low-dose PEM with the radiotracer fluorine 18-labeled fluorodeoxyglucose ( 18 F-FDG). Two breast radiologists reviewed PEM images taken one and four hours post 18 F-FDG injection and correlated the findings with lab results.

PEM displayed comparable performance to MRI, identifying 24 of the 25 invasive cancers (96%). Its false positive rate was only 16%, compared with 62% for MRI.

Along with its strong sensitivity and low false-positive rate, PEM could potentially decrease downstream healthcare costs as this study shows it may prevent further unnecessary work up compared to MRI. Additionally, the technology is designed to deliver a radiation dose comparable to that of traditional mammography without the need for breast compression, which can often be uncomfortable for patients.

"The integration of these features -- high sensitivity, lower false-positive rates, cost-efficiency, acceptable radiation levels without compression, and independence from breast density -- positions this emerging imaging modality as a potential groundbreaking advancement in the early detection of breast cancer," said study lead author Vivianne Freitas, M.D., M.Sc., assistant professor at the University of Toronto. "As such, it holds the promise of transforming breast cancer diagnostics and screening in the near future, complementing or even improving current imaging methods, marking a significant step forward in breast cancer care."

Low-dose PEM offers potential clinical uses in both screening and diagnostic settings, according to Dr. Freitas.

"For screening, its ability to perform effectively regardless of breast density potentially addresses a significant shortcoming of mammography, particularly in detecting cancers in dense breasts where lesions may be obscured," she said. "It also presents a viable option for patients at high risk who are claustrophobic or have contraindications for MRI."

The technology could also play a crucial role in interpreting uncertain mammogram results, evaluating the response to chemotherapy and ascertaining the extent of disease in newly diagnosed breast cancer, including involvement of the other breast.

Dr. Freitas, who is also staff radiologist of the Breast Imaging Division of the Toronto Joint Department of Medical Imaging, University Health Network, Sinai Health System and Women's College Hospital, is currently researching PEM's ability to reduce the high rates of false positives typically associated with MRI scans. Should PEM successfully lower these rates, it could significantly lessen the emotional distress and anxiety linked to false positives, Dr. Freitas said. Additionally, it might lead to a decrease in unnecessary biopsies and treatments.

More studies are needed to determine low-dose PEM's exact role and efficacy in the clinical setting.

"While the full integration of this imaging method into clinical practice is yet to be confirmed, the preliminary findings of this research are promising, particularly in demonstrating the capability of detecting invasive breast cancer with low doses of fluorine-18-labeled FDG," Dr. Freitas said. "This marks a critical first step in its potential future implementation in clinical practice."

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Story Source:

Materials provided by Radiological Society of North America . Note: Content may be edited for style and length.

Journal Reference :

  • Vivianne Freitas, Xuan Li, Anabel Scaranelo, Frederick Au, Supriya Kulkarni, Sandeep Ghai, Samira Taeb, Oleksandr Bubon, Brandon Baldassi, Borys Komarov, Shayna Parker, Craig A. Macsemchuk, Michael Waterston, Kenneth O. Olsen, Alla Reznik. Breast Cancer Detection Using a Low-Dose Positron Emission Digital Mammography System . Radiology: Imaging Cancer , 2024; 6 (2) DOI: 10.1148/rycan.230020

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Risk-reducing mastectomy may lower breast cancer mortality: Study

Risk-reducing mastectomy may lower breast cancer mortality: Study

Risk-reducing mastectomies (RRM) in women with a certain genetic variant may significantly reduce the risk of being diagnosed with breast cancer and lower the probability of death, a study has found.

The research, published in the British Journal of Cancer, examined how RRM -- a surgery to remove a breast -- affects the rate of death of women with a pathogenic variant but no cancer diagnosis.

''The decision to have a risk reducing mastectomy is often difficult for a woman to make, and the more evidence we are able to provide them with when they are making that decision, the more informed their care plan will be,'' said Professor Kelly Metcalfe from the University in Toronto, Canada.

Women who have an inherited BRCA1 or BRCA2 variant have an 80 per cent risk of developing breast cancer over the course of their lifetime, the researchers said.

Studies have shown that an RRM reduces the risk of breast cancer by 90 per cent, and in Canada, 30 per cent of women with a pathogenic variant opt for this surgery, they said.

It is one of the most effective ways of preventing breast cancer in women with this risk profile, Metcalfe said.

The researchers followed over 1600 participants from a registry of women with a pathogenic BRCA 1/2 variant from nine different countries over the course of six years, with half of the women having a risk-reducing mastectomy.

At the end of the trial, there were 20 incident breast cancers and two deaths in the group who opted for a RRM, and 100 incident breast cancers and seven deaths in the control group, the researchers said.

RRM reduced the risk of breast cancer by 80 per cent, and the probability of dying of breast cancer 15 years after risk-reducing mastectomy was less than one per cent, they said.

''Although there wasn't a significant difference in deaths between the two groups in this study, we know that a risk reducing mastectomy significantly reduces the risk of ever developing breast cancer,'' said Metcalfe.

Metcalfe noted that following these participants for an extended period would generate more evidence to assess the true mortality risk with precision and highlight the benefits associated with this type of surgery.

''Right now, we have good screening in place for breast cancer, including breast MRI, so surgery is only offered as an option, not a recommendation,'' Metcalfe said.

''But with more studies being conducted to assess women's trajectory and risk factors following RRM, we will know whether these guidelines need to be changed in the future,'' she added.

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male breast cancer case study

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male breast cancer case study

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  • v.20(6); 2015 Jun

Logo of oncologist

Male Breast Cancer: A Study in Small Steps

Much can be learned from small single-institution studies in male breast cancer; however, individual studies represent only small steps toward our understanding of this rare disease. International collaborative efforts are necessary to make the great strides needed to discern the unique biology, genetics, and optimal treatment for male breast cancer and to best serve patients with this disease.

In this issue of The Oncologist , two articles discuss the management of men with breast cancer or a predisposition to breast cancer. Masci et al. describe clinicopathologic characteristics, treatment, and outcomes of 91 men with invasive breast cancer diagnosed between 2000 and 2013 [ 1 ]. Mitri et al. describe BRCA mutation testing results and BRCAPRO modeling in 146 men presenting for genetic evaluation at the MD Anderson Cancer Center between February 1997 and September 2011 [ 2 ]; 48 of the men studied had a history of breast cancer.

Male breast cancer (mBC) is understudied because of its rarity. Consequently, management of mBC is based largely on extrapolation of data from studies of female breast cancer. Emerging data, from the study by Masci et al. [ 1 ] and others [ 3 , 4 ] suggest that there are several unique characteristics of male breast cancer compared with female breast cancer, including a higher rate of hormone positivity, lower HER2 positivity, and more advanced presentation at diagnosis. A large retrospective international study of male breast cancer, presented at the San Antonio Breast Cancer Symposium in December 2014, included 1,483 patients and noted rates of ER and HER2 positivity comparable to the analysis presented by Masci et al., as well as a similar distribution of grade and nodal status. Interestingly, in both studies, although a majority of patients had stage I or II disease, relatively few patients underwent lumpectomy (9% in the series by Masci et al. and 4% in the international series).

Of note, Masci et al. described both treatment patterns and patient outcomes [ 1 ]. In their study, 22% of patients received therapy with an aromatase inhibitor. Of 14 patients who received an aromatase inhibitor as adjvuant therapy, 6 (42%) developed recurrent disease. In addition, in men treated with aromatase inhibitors in the metastatic setting, only 1 of 9 patients had stable disease for more than 12 months. None of the patients received concomitant therapy with a gonadotropin-releasing hormone (GnRH) agonist. Preclinical data suggest that men do not have as complete suppression of estrogen with aromatase inhibitors as seen in women. Furthermore, aromatase inhibitors may increase circulating testosterone, leading to an increase in androgen available for conversion to estrogen. Consequently, although aromatase inhibitors are the treatment of choice for postmenopausal female breast cancer, it is generally not considered the standard for mBC. Clinical data suggest lower efficacy for aromatase inhibitors as sole hormonal therapy [ 5 , 6 ], although the addition of GnRH analogs may be beneficial. In the absence of clinical trial data supporting the efficacy of aromatase inhibitors in mBC, tamoxifen should be considered the standard of care.

Masci et al. also noted a high rate of second cancers among men with breast cancer in their series [ 1 ], a finding also seen in other studies [ 7 , 8 ]. Eighteen percent of patients developed a second malignancy, most commonly prostate cancer (31%) and colon cancer (19%). Although these cancers are both common in elderly men, this finding highlights the issue of hereditary cancer syndromes in men diagnosed with breast cancer. Unfortunately, in this study, only a small percentage of patients studied underwent BRCA mutation testing (11 patients were tested; 1 was found to have a mutation in BRCA1 , one had a BRCA2 mutation, and one had a BRCA1 variant of uncertain significance). Although many of these patients were not treated in the modern era, these findings highlight the need for genetic evaluation and counseling for all men presenting with breast cancer.

Clinical practice guidelines currently recommend BRCA mutation testing for all men diagnosed with breast cancer. Also in this issue of The Oncologist , Mitri et al. described their work validating the BRCAPRO model in men presenting for genetic evaluation, including those with a diagnosis of breast cancer [ 2 ]. The BRCAPRO model takes into account personal history of cancer, first- and second-degree family history, age at cancer diagnosis, current age or age at death of included individuals, ethnicity (including Ashkenazi Jewish ancestry), and history of risk-reducing surgeries. The BRCAPRO model has been validated as a tool for determining risk of carrying a BRCA mutation in multiple settings [ 9 – 11 ] but has not been studied specifically in men. In this series, 33% of the evaluated male patients had a personal history of breast cancer [ 2 ]. The cohort also included men with a personal history of prostate and pancreatic cancer, those with a family history of cancer, and those with a known BRCA mutation in a family member. This study is the first validation of the BRCAPRO model in men being seen by a medical genetics professional. The authors found that the model had acceptable sensitivity, specificity, and positive and negative predictive value in the study cohort. A valid risk-prediction model could potentially be used to more accurately assess which patients should proceed to genetic testing; therefore, these results provide reassurance regarding the validity of BRCAPRO in men and may have clinical implications for some patients, particularly those with a family history of breast cancer or with a personal history of pancreatic or prostate cancer. It should be noted, however, that a large portion of patients included in this study were men with a personal history of breast cancer and with a known BRCA1 or BRCA2 mutation in the family; for such patients, genetic testing should be performed regardless of prior probability based on risk modeling.

Although both studies provide valuable information [ 1 , 2 ], these two papers also serve as a reminder of the gaps in our knowledge about mBC. No randomized clinical trials to date have evaluated treatment of men with breast cancer. We continue to extrapolate from data from female patients to make clinical treatment decisions, despite growing evidence of biological differences between male and female breast cancer. The use of aromatase inhibitors in the treatment of male breast cancer is a case in point. Furthermore, the genetics of male breast cancer remains poorly described. The data show clearly that BRCA2 and, to a lesser extent, BRCA1 increase risk of male breast cancer, but a large portion of breast cancer in men remains unexplained by mutations in these genes. Additional genes, such as PALB2, CHEK2, PTEN , and BRIP1 have also been implicated in mBC [ 11 – 15 ], and other risk factors have been described [ 16 ]. With the recent advent and availability of multigene panels for genetic testing in those with a suspected hereditary cancer predisposition, it is likely that additional genetic mutations that increase risk of mBC will be identified; however, much remains to be learned about the etiology and genetic basis of male breast cancer. An international consortium of investigators, led by the European Organization for Research and Treatment of Cancer (EORTC) and the Translational Breast Cancer Research Consortium (TBCRC), recently presented the results of a retrospective study in 1,483 patients with male breast cancer that included central pathology review [ 3 ]. This group has recently initiated a prospective cohort study of male breast cancer that will include the collection of DNA and tumor samples and hopefully will lead to great strides in our understanding of male breast cancer biology, genetics, treatment, and outcomes. This effort will also provide the infrastructure on which to build future clinical trials in mBC.

In conclusion, much can be learned from small single-institution studies in male breast cancer; however, individual studies represent only small steps toward our understanding of this rare disease. International collaborative efforts are necessary to make the great strides needed to discern the unique biology, genetics, and optimal treatment for male breast cancer and to best serve our patients with this disease.

Editor's Note: See the related articles on pages 586 and 593 of this issue.

Disclosures

Larissa A. Korde: Amgen (C/A).

(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board

IMAGES

  1. male breast cancer case study

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  3. (PDF) Male Breast Cancer: Case Studies and Literature Review

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  4. Male breast cancer case study

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  5. Tara PowerPoint Male Breast Cancer

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  6. Tara PowerPoint Male Breast Cancer

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COMMENTS

  1. A Case of Locally Advanced Breast Cancer in a 59-Year-Old Man Requiring a Modified Approach to Management

    Background. Worldwide, male breast cancer is extremely rare, accounting for <1% of all breast tumors and <1% of all malignancies in men [1-3].Recently, the incidence of male breast cancer has increased from 1.0 per 100,000 men in the late 1970s to 1.2 per 100,000 men from 2000 to 2004 [4-7].The American Cancer Society reported a similar trend in the incidence of breast cancer in men from ...

  2. Male breast cancer: a report of 25 cases

    PMID: 33738031 Male breast cancer: a report of 25 cases Majdouline El Fouhi, 1,& Abdelhalim Mesfioui, 1 and Abdellatif Benider 2 Author information Article notes Copyright and License information PMC Disclaimer Go to: Abstract Male breast cancer is a rare disease accounting for less than 1% of all breast cancer diagnoses worldwide to our knowledge.

  3. A case report of male breast cancer in a very young patient: What is

    8 Citations 1 Altmetric Metrics Abstract Male breast cancer accounts for 1% of all breast cancer cases, and men tend to be diagnosed at an older age than women (mean age is about 67 years). Several risk factors have been identified, such as genetic and hormonal abnormalities.

  4. Management of Male Breast Cancer: ASCO Guideline

    Male breast cancer is a rare disease representing < 1% of all breast carcinomas diagnosed in the United States each year. In 2019, an estimated 2,670 new cases of breast cancer were expected to be diagnosed among men in the United States, and about 500 men were expected to die as a result of breast cancer. 1 The lifetime risk of breast cancer is about 1:1,000 for a man, whereas it is ...

  5. Male Breast Cancer: An Updated Review of Epidemiology, Clinicopathology

    Introduction Breast cancer in men is a relatively rare disease and accounts for only 1% of the breast cancer population. As with all other rare diseases, it has been challenging to conduct prospective clinical studies in male breast cancer (MaBC) as evidenced by several prematurely closed clinical trials due to the lack of enrollment.

  6. Breast Cancer in Men

    The Male Breast Cancer Pooling Project conducted a nested case-control study of estrogen and androgen levels in relation to the risk of breast cancer in men. Although androgen levels...

  7. Clinicopathologic characteristics and prognosis for male breast cancer

    1 Altmetric Metrics Abstract Male breast cancer (MBC) is rare. Due to limited information, MBC has always been understudied. We conducted a retrospective population-based cohort study using...

  8. Case Series Analysis of Male Breast Cancer

    1 Citation Explore all metrics Abstract Male breast cancer is a rare disease, accounting for less than 1% of all cases of breast cancer. However, the incidence of male breast cancer is increasing.

  9. Inflammatory Breast Cancer in Men: A rare clinical case report and a

    Abstract The initial misdiagnosis and delayed treatment for inflammatory breast cancer in men is brought about by its rarity and lack of readily available guidelines on pathways. A 78-year-old male presented to the breast clinic with an abscess and was later diagnosed with inflammatory breast cancer.

  10. Male Breast Cancer: Three Case Reports and A Literature Review

    PMID: 37605409 DOI: 10.2174/1871520623666230821124008 Abstract Introduction: Male breast cancer (MBC) accounts for 0.5%-1% of all breast cancers diagnosed worldwide. However, its biological characteristics can be distinguished from that of female breast cancer (FBC).

  11. Male breast cancer

    Summary Occurrence of male breast cancer, a rare disease, peaks at age 71 years. Familial cases usually have BRCA2 rather than BRCA1 mutations. Occupational risks include high temperature environments and exhaust fumes, but electromagnetic fields have not been implicated.

  12. The Male Breast Cancer Study

    It has helped researchers to find a key genetic change in a genece called RAD51B linked breast cancer in men. This single change can increase the risk fo breast cancer by up to 50%. Recently, the study found three more genetic changes that increased the risk of developing breast cancer in men by approximately 47%, 45% and 61% respectively.

  13. Finasteride Use and Risk of Male Breast Cancer: A Case-Control Study

    AbstractBackground:. In case reports, concerns have been raised as to whether finasteride use increases the risk of male breast cancer. Previous epidemiologic evidence on the potential link is conflicting. This study aimed to assess whether an association between finasteride use and male breast cancer exists after accounting for potential confounders.Methods:. The source population consisted ...

  14. Infertility and risk of breast cancer in men: a national case-control

    Purpose Breast cancer is uncommon in men and its aetiology is largely unknown, reflecting the limited size of studies thus far conducted. In general, number of children fathered has been found a risk factor inconsistently, and infertility not. We therefore investigated in a case-control study, the relation of risk of breast cancer in men to infertility and number of children. Patients and ...

  15. The efficacy of palbociclib and ribociclib in the first-line ...

    Introduction Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 −) breast cancer in ...

  16. Occupational exposures and male breast cancer: A nested case-control

    Family history of breast cancer and genetic mutations, especially in the BRCA2 gene, and to a lesser extent in BRCA1, CHEK2 and PALB2 genes are risk factors for MBC [1]. Some hormone-related factors such as Klinefelter's syndrome, obesity, Methods. We conducted a case-control study nested within the Nordic Occupational Cancer Study (NOCCA ...

  17. Occupational exposures and male breast cancer: A nested case-control

    Occupational exposures and male breast cancer: A nested case-control study in the Nordic countries Breast. 2019 Dec;48:65-72. doi: 10.1016/j.breast.2019.09.004. Epub 2019 Sep 12. Authors ... Background: Male breast cancer (MBC) is a rare and understudied disease. There is limited evidence on association between environmental and occupational ...

  18. Clinicopathological Features and Treatment Outcomes of Male Breast

    Male breast cancer occurs at a relatively earlier age in Pakistani population as compared with Western men. Mastectomy is the preferred surgical option for MBC on account of the advanced disease and delayed presentation. ... A 10-Year Retrospective Cross-Sectional Study Breast Cancer (Auckl). 2024 Feb 17:18:11782234241233120. doi: 10.1177 ...

  19. An Update on the General Features of Breast Cancer in Male Patients—A

    1. Introduction Female breast cancer is the most frequently diagnosed tumor and one of the leading causes of cancer-related mortality worldwide. Male breast cancer is uncommon, representing less than one percent of all breast cancers.

  20. Male Breast Cancer Results

    The study included 71 men with breast cancer (called "cases") and 373 men who had other types of cancer (called "controls"). ATSDR used the Department of Veteran's Affairs (VA) cancer registry to identify these cases and controls.

  21. Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the

    Case Records of the Massachusetts General Hospital Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic Laura M. Spring, M.D., Michelle C. Specht, M.D.,...

  22. A case report of male breast cancer in a very young patient: What is

    Male breast cancer accounts for 1% of all breast cancer cases, and men tend to be diagnosed at an older age than women (mean age is about 67 years). Several risk factors have been identified, such as genetic and hormonal abnormalities.

  23. Risk factors for male breast cancer--a case-control study from

    PMID: 11504305 We report a population-based case-control study on risk factors for male breast cancer. Data on a broad range of previously suggested risk factors were collected in a set of Scandinavian breast cancer cases and matched controls.

  24. Male Breast Cancer

    A Continuing Debate. Molecular profiling of male breast cancer - lost in translation? Although breast cancer is typically synonymous as a disease that commonly occurs in women, it does occur in men as well.

  25. Novel technique has potential to transform breast cancer detection

    For the study, 25 women, median age 52, recently diagnosed with breast cancer, underwent low-dose PEM with the radiotracer fluorine 18-labeled fluorodeoxyglucose (18 F-FDG).

  26. Risk-reducing mastectomy may lower breast cancer mortality: Study

    Risk-reducing mastectomies (RRM) in women with a certain genetic variant may significantly reduce the risk of being diagnosed with breast cancer and lower the probability of death, a study has found. The research, published in the British Journal of Cancer, examined how RRM -- a surgery to remove a breast -- affects the rate of death of women ...

  27. Male Breast Cancer: A Study in Small Steps

    Emerging data, from the study by Masci et al. [ 1] and others [ 3, 4] suggest that there are several unique characteristics of male breast cancer compared with female breast cancer, including a higher rate of hormone positivity, lower HER2 positivity, and more advanced presentation at diagnosis.