Research Paper On Breast Cancer In Men

A Review of the Diagnosis and Management of Male Breast Cancer

  1. Sharon H. Giordano
  1. Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA
  1. Sharon H. Giordano, M.D., M.P.H., Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 424, Houston, Texas 77030, USA. Telephone: 713-792-2817; Fax: 713-794-4385; e-mail: sgiordan{at}
  • Received September 2, 2004.
  • Accepted May 24, 2005.


Male breast cancer is an uncommon disease although the incidence has increased over the past 25 years. As with many other rare “orphan” diseases, male breast cancer is understudied. The rarity of the disease precludes prospective randomized clinical trials. In addition, few researchers and minimal funding have focused on breast cancer in men, but further work is clearly needed to better understand this disease. It shares many similarities with breast cancer in women; yet some clear differences have emerged. In this article, the latest information on the epidemiology, biology, and treatment of male breast cancer is reviewed.

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Male breast cancer is an uncommon disease that has been the focus of limited research. Because this disease is rare, no randomized trials have been possible, and only one prospective therapeutic study has been published [1]. Most information on breast cancer in men has been collected from retrospective studies spanning several decades, and treatment recommendations have been extrapolated from results of trials in female patients. Because the incidence of male breast cancer is rising [2], there has been an increasing interest in this disease. In this article, the latest information on the epidemiology, genetics, biologic characteristics, and clinical aspects of male breast cancer is covered.

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Epidemiology and Risk Factors

In 2005, an estimated 1,690 new cases of male breast cancer will be diagnosed in the U.S., and 460 men will die as a result of breast cancer [3]. Male breast cancer accounts for only 0.7% of all breast cancer diagnoses [4]. The mean age at diagnosis for men with breast cancer is 67 years, which is 5 years older than the average age at diagnosis for women [2]. However, breast cancer has been reported in male patients ranging in age from 5–93 years [5]. The incidence of male breast cancer increases with advancing patient age, climbing steadily until a plateau is reached around age 80 [5, 6]. As in breast cancer in women, breast cancer in men has been increasing; the incidence has climbed 26% over the past 25 years [2]. Yet the overall incidence in the U.S. remains low: approximately one case per 100,000 population per year [7].

The etiology of male breast cancer is unclear, but hormonal levels may play a role in the development of this disease. Testicular abnormalities such as undescended testes, congenital inguinal hernia, orchiectomy, orchitis, and infertility have been consistently associated with elevations in breast cancer risk [8,9]. Benign breast conditions, including history of breast trauma and nipple discharge, have also been reported to increase risk [8, 9]. Whether gynecomastia is a risk factor for male breast cancer is unclear. Gynecomastia has been reported in association with breast cancer in men [10, 11], but is also very common in healthy men [12]. Klinefelter’s syndrome, in which patients carry XXY chromosomes, may be present in 3%–7% of men with breast cancer, giving males with Klinefelter’s syndrome a 50-fold greater risk over the general male population [13–15]. Men with a family history of breast cancer in a female relative have 2.5 times the odds of developing breast cancer [16]. As in women, exposure to chest wall radiation, such as in patients previously treated with mantle radiation for Hodgkin’s disease, increases the risk of a subsequent breast cancer [8]. Alcohol use, liver disease, obesity, electromagnetic field radiation, and diet have all been proposed as risk factors, but findings have been inconsistent across studies [17–24].

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BRCA1 and BRCA2 are breast cancer susceptibility genes that are responsible for a proportion of cases of heritable breast cancer. In women, mutations in these genes confer a 40%–70% lifetime risk of breast cancer. Mutations in BRCA1 and BRCA2 also increase the risk of affected men developing breast cancer, although not to the same absolute risk as in women (Table 1⇓). BRCA1 mutations have been reported in men with breast cancer, although they do not appear to be a common cause of male breast cancer [25–30]. In series of high-risk families undergoing genetic testing, 10%–16% of men with breast cancer have been reported to have BRCA1 mutations [27, 28]. In population-based series of men with breast cancer unselected by family history, BRCA1 mutations are much less common; 0%–4% of men with breast cancer harbor this mutation [25, 29–31]. Mutations in the BRCA2 gene are more frequent in males with breast cancer, with 4%–16% of men with breast cancer reported to be mutation carriers in population-based series [29–31]. The highest known prevalence is in Iceland, where a founder mutation is present in 40% of men with breast cancer [32]. Male breast cancer in patients with BRCA2 mutations tends to present at a younger age and may be associated with a poorer survival [33]. Because of the prevalence of these mutations in male breast cancer patients, genetic counseling and testing should be considered.

Other genes have been investigated for a potential role in the etiology of male breast cancer, but none has clearly been associated with an increased risk. Mutations in the androgen receptor gene, PTEN (Cowden’s syndrome), and mismatch repair genes (hMLH1) have been reported in male patients with breast cancer [34–38]. However, none of these genes has been demonstrated to have a causal association with male breast cancer. Further studies are needed to elucidate their role.

Table 1.

BRCA1 and BRCA2 mutations in male breast cancer

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Pathologic Characteristics

Ductal carcinoma in situ comprises approximately 10% of breast cancers in men [2, 39]. The most common growth patterns are papillary and cribriform, and the majority of these tumors are low grade [39, 40]. Lobular carcinoma in situ is very rare because the male breast lacks terminal lobules, but has been reported in association with invasive lobular carcinoma [41]. For invasive carcinomas, the ranges of histologic subtypes for female and male breast cancer are similar, but the relative distributions differ [2]. Data from more than 2,000 male patients in the Surveillance, Epidemiology, and End Results (SEER) cancer registry show that 93.7% of male breast cancers are ductal or unclassified carcinomas, 2.6% are papillary, 1.8% are mucinous, and only 1.5% are lobular [2]. This distribution is in contrast to that seen in female breast cancer, in which almost 12% of cancers are lobular carcinomas.

Male breast cancers have high rates of hormone-receptor expression. Approximately 90% of male breast cancers express the estrogen receptor, and 81% express the progesterone receptor [2]. Cancers of the male breast are significantly more likely than cancers of the female breast to express hormone receptors, even after adjustment for tumor stage, grade, and patient age [2, 42–44]. As in female breast cancer, the rates of hormone-receptor positivity increase with increasing patient age [2]. In contrast, the her2-neu proto-oncogene is less likely to be overexpressed in cancers of the male breast [45, 46]. Early reports had suggested equivalent rates of her2-neu overexpression between male and female breast cancers [47, 48]. However, those studies were performed before improved standardization of methodology and probably overestimated her2-neu overexpression. A recent series of 75 patients found that only 5% of male breast cancers overexpressed her2-neu [46]. Similarly, Bloom et al. found that only one of 58 male breast cancers overexpressed her2-neu and that zero of 58 had gene amplification [45]. The role of the androgen receptor in male breast cancer is unclear. The reported rates of androgen-receptor expression have ranged from 34%–95%, but this receptor has not been associated with breast cancer prognosis [49–51].

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Clinical Features

The most common presenting symptoms in male breast cancer patients are a painless subareolar lump, nipple retraction, and bleeding from the nipple [10, 52, 53]. As in women, there is a slight preponderance of left-sided versus right-sided disease [54]. Usually the primary consideration in the differential diagnosis is gynecomastia, which affects approximately 30% of healthy men [55]. Mammography can be helpful in differentiating gynecomastia from malignant breast disease. An example of a mammogram performed in a male patient with an invasive ductal carcinoma is shown in Figure 1⇓. Malignant breast tumors are more often eccentric and have irregular spiculated edges [56, 57]. The sensitivity and specificity of mammography for the diagnosis of male breast cancer have been reported to be 92% and 90%, respectively [56]. Ultrasonography can also be a useful adjunct and provide information regarding nodal involvement. After appropriate local imaging, any suspicious mass needs to be biopsied to confirm the diagnosis. Estrogen receptor, progesterone receptor, and her2-neu status should be evaluated in every patient, as these may affect the clinical management. The extent of disease can be determined from laboratory evaluation, chest radiography, bone scan, and computed tomography scan of the abdomen, as clinically appropriate. Tumor stage is determined using the American Joint Committee on Cancer classification system, which considers tumor size, nodal involvement, and distant metastases [58].

Figure 1.

Mammogram of male patient with a 1.8-cm invasive ductal carcinoma in the right breast.

Tumor size and lymph node involvement are two clear prognostic factors for male patients with breast cancer [2]. Men with tumors measuring 2–5 cm have a 40% higher risk of death than men with tumors <2 cm in maximum diameter [2]. Similarly, men with lymph node involvement have a 50% higher risk of death than those without lymph node involvement [2]. As in women, an increasing number of involved axillary lymph nodes is associated with a poorer prognosis [59]. In univariate analyses, negative hormone-receptor status and high tumor grade were associated with poorer survival, but these factors do not appear to have independent prognostic value on multivariate analysis [2, 60–62]. In general, the prognosis for male and female patients with breast cancer is similar [2, 54]. Overall survival rates are lower for men, but this is due to an older age at diagnosis and more advanced disease at presentation [2]. When survival is adjusted for age at diagnosis and stage of disease, outcomes are comparable [2]. Disease-specific and overall survival rates by stage of disease for male patients are shown in Table 2⇓ and are illustrated in Figure 2⇓ and Figure 3⇓. Disease-specific survival rates are notably higher than overall survival rates due to the older average age of this population and deaths from other comorbid illnesses.

Figure 2.

Kaplan-Meier curves for overall survival. This analysis includes 1,986 male breast cancer patients diagnosed in 1988–2001 in the Surveillance, Epidemiology, and End Results cancer registry [7].

Figure 3.

Kaplan-Meier curves for disease-specific survival. This analysis includes 1,986 male breast cancer patients diagnosed in 1988–2001 in the Surveillance, Epidemiology, and End Results cancer registry [7].

Table 2.

Disease-specific and overall survival rates in male breast cancer among 1,986 male patients in the Surveillance, Epidemiology, and End Results database, diagnosed in 1988–2001

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Treatment of Early-Stage Disease

Local therapy for breast cancer is generally similar in men and women. Most men are treated with modified radical mastectomy with axillary lymph node dissection or sentinel node biopsy [54]. Historically, radical mastectomy was often performed, but retrospective studies indicate that the outcome for men is equally good when treated with less invasive surgery [63, 64]. Larger studies from female breast cancer patients also support the use of modified radical mastectomy over radical mastectomy [65, 66]. Axillary lymph node dissection is clearly an important component of therapy, because men who have nodal dissection omitted tend to have poorer outcomes [11, 67]. For instance, in a series of 397 patients with male breast cancer, 13% of patients without axillary dissection developed regional nodal recurrence compared with 1.2% of patients who underwent axillary dissection [67]. Sentinel node biopsy has been recently evaluated in male patients (Table 3⇓) [68–70]. Due to the rarity of this disease, large studies establishing the sensitivity and specificity of sentinel node biopsy in male breast cancer are not possible. However, several case series have been published that have established the feasibility of sentinel node biopsy in the male patient with breast cancer [68–72]. Among a total of 56 male patients combined from these reports, the sentinel node was successfully identified in all but one patient [68–72]. A combined total of 11 patients with a negative sentinel node biopsy underwent confirmatory axillary dissection, and none had any additional nodes [68–72]. This procedure is now being increasingly used in male patients who are clinically node-negative.

There are limited data regarding the indications for adjuvant radiation therapy in male patients, but generally similar guidelines are recommended in men as in women. Men do tend to be treated with radiation therapy more often after mastectomy than women, perhaps because they are more likely to have nipple or skin involvement [54]. Radiation therapy does appear to be effective in preventing local recurrences in male patients, but all studies have been underpowered to address the question of a potential survival benefit [62, 67, 73, 74]. To determine which male patients would derive benefit from adjuvant radiation, Perkins et al. studied a series of 142 male patients treated at The University of Texas M. D. Anderson Cancer Center [75]. Overall, 18% of patients experienced locoregional failure, with the most common sites of relapse being the chest wall and supraclavicular areas. Predictors of local regional failure included margin status, tumor size, and the number of involved axillary lymph nodes. Focal skin involvement was not associated with a higher risk of local recurrence.

As for women with breast cancer, adjuvant chemotherapy is used to treat male patients who have a substantial risk of recurrence and death from breast cancer. Whereas the data supporting adjuvant chemotherapy in women are strong [76], there is little information on the effectiveness of adjuvant chemotherapy in men. The limited data that have been published, however, do support a similar benefit in male and female patients. One prospective study of adjuvant chemotherapy in men has been published [1]. A series of 24 male patients with stage II breast cancer was treated at the National Cancer Institute with adjuvant CMF (cyclophosphamide, methotrexate, and fluorouracil). The projected 5-year survival rate was >80%, which was significantly higher than a similar cohort of historical controls. Retrospective series have also suggested that adjuvant chemotherapy lowers the risk for recurrence in male patients [11, 77, 78]. Given the established benefit of chemotherapy in women and the suggestive evidence in men, most clinicians use similar guidelines for adjuvant chemotherapy in male and female patients. For instance, at The University of Texas M. D. Anderson Cancer Center, chemotherapy is offered to those patients with breast tumors measuring >1 cm and to those patients with lymph node involvement. Anthracycline-based chemotherapy is offered to those patients without lymph node involvement, whereas both anthracyclines and taxanes are used for those patients with lymph node involvement. An algorithm for the treatment of male breast cancer is illustrated in Figure 4⇓.

Figure 4.

Treatment algorithm for male breast cancer.

Adjuvant hormonal therapy clearly has a role in male breast cancer patients with hormone receptor–positive tumors [10, 60, 79]. Many retrospective series have evaluated the effectiveness of tamoxifen (Nolvadex®; AstraZeneca Pharmaceuticals, Wilmington, DE, in male breast cancer. In the metastatic setting, tamoxifen clearly has activity against male breast cancer [52]. The retrospective series that have evaluated tamoxifen in the adjuvant setting have shown a reduced risk of breast cancer recurrence and death [10, 60, 79, 80]. Given that such a high proportion of males with breast cancer have tumors that express the estrogen or progesterone receptor, most male patients can benefit from adjuvant tamoxifen. The toxicities of tamoxifen in the male patient have not been extensively studied. One series reported that men had some difficulty tolerating this drug, and side effects, including deep-vein thrombosis, decreased libido, impotence, mood alterations, and hot flashes, have been noted [81].

The role of aromatase inhibitors in the adjuvant setting for male patients is limited. One case series of five patients with metastatic disease treated with aromatase inhibitors has been published [82]. Of the five patients, three had a period of disease stability, but these patients had indolent disease prior to the addition of an aromatase inhibitor. No patients had objective responses. Anastrozole (Arimidex®; AstraZeneca Pharmaceuticals) has been tested in healthy male volunteers [83]. Men treated with anastrozole did not appear to have as complete estrogen suppression as is seen in women; a 50% decrease in estradiol concentrations was seen. In addition, therapy with anastrozole raised testosterone levels by 58%. However, two recent case reports have described responses in male patients treated with letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ, [84, 85]. Clearly, further investigation is needed to determine the efficacy of aromatase inhibitors in male patients. For now, there are insufficient data to recommend an aromatase inhibitor in the adjuvant setting for male patients.

Table 3.

SLN biopsy in male breast cancer

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Treatment of Metastatic Disease

In general, the approach to the treatment of metastatic breast cancer is similar in male and female patients with breast cancer. Given that the vast majority of men have estrogen receptor–positive tumors, hormonal therapy is often the first approach. Farrow and Adair reported on the first male patient to respond to hormonal therapy [86].They described a male with metastatic breast cancer who had tumor regression after orchiectomy. Although, historically, surgical ablative therapies such as orchiectomy, adrenalectomy, and hypophysectomy have been used effectively to control metastatic breast cancer in male patients, these surgical procedures are rarely used today and have been supplanted by additive hormonal therapies. Tamoxifen has established efficacy in metastatic male breast cancer, with an approximate 50% response rate, and is considered the preferred first-line approach [87]. Luteinizing hormone–releasing hormone agonists, with or without antiandrogens, have also been reported to be effective in male breast cancer [88–90]. There have been case reports of responses to a wide variety of hormonal therapies including progestins, androgens, steroids, aminoglutethamide, estrogens, and letrozole [84, 85, 87]. The role of fulvestrant (Faslodex®; AstraZeneca Pharmaceuticals) remains unclear. For male patients with hormone-refractory disease or rapidly progressing visceral metastases, chemotherapy can provide significant palliation. Generally, a similar approach is used for chemotherapy in metastatic male breast cancer as in female breast cancer. The effectiveness of trastuzumab (Herceptin®; Genentech, Inc., South San Francisco, CA, in her2-neu overexpressing male breast cancer is unproven, but certainly seems reasonable given the strong evidence in support of trastuzumab in women with breast cancer.

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Second Primaries

Male breast cancer survivors have an increased risk of developing second primary cancers. Data from the Swedish Family-Cancer Database indicate that men with breast cancer have a 93-fold greater risk of developing contralateral breast cancer than men with no history of breast cancer [91]. The absolute risk for an individual male patient developing contralateral breast cancer was 1.75%. Auvinen et al. reported similar findings from the SEER cancer registry database; men with a history of breast cancer had a 30-fold greater risk of contralateral breast cancer [92]. The risk for other cancers, including melanoma and prostate cancer, may also be elevated in male breast cancer survivors, particularly in mutation carriers [92].

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Male breast cancer remains a rare disease, although the incidence is increasing. While breast cancer in men is similar to female breast cancer, there are distinct features that should be appreciated. Risk factors include many conditions that could affect hormonal levels, a family history of breast cancer, Klinefelter’s syndrome, and a prior history of radiation exposure. BRCA1 mutations are associated with some cases, but the link between BRCA2 mutations and male breast cancer is stronger. Men tend to be diagnosed at an older age than women and with later stage disease. Most of the histologic subtypes that are seen in women are also present in men, except that lobular histology is much rarer. Tumors of the male breast are more likely to express the estrogen and progesterone receptors and less likely to overexpress her2-neu than breast cancers in women. Sentinel node biopsy appears feasible in male patients, but the data regarding this procedure in the male breast are limited. Chemotherapy and adjuvant radiation should be offered in clinical situations in which these treatments would be deemed appropriate in women. Given the high prevalence of hormone receptor–positive disease, adjuvant hormonal therapy has an important role in the treatment of the male patient. Tamoxifen remains the gold standard of adjuvant hormonal therapies; the data on aromatase inhibitors are sparse, and these drugs should not currently be used in the adjuvant setting. Future studies with a focus on disease biology are crucial to advance the understanding of male breast cancer and to optimize the care of all male patients.


  1. Bagley CS, Wesley MN, Young RC et al. Adjuvant chemotherapy in males with cancer of the breast. Am J Clin Oncol1987;10:55–60.

  2. Giordano SH, Cohen DS, Buzdar AU et al. Breast carcinoma in men: a population-based study. Cancer2004;101:51–57.

  3. Jemal A, Murray T, Ward E et al. Cancer statistics, 2005. CA Cancer J Clin2005;55:10–30.

  4. Jemal A, Tiwari RC, Murray T et al. Cancer statistics, 2004. CA Cancer J Clin2004;54:8–29.

  5. Crichlow RW. Carcinoma of the male breast. Surg Gynecol Obstet1972;134:1011–1019.

  6. Ewertz M, Holmberg L, Karjalainen S et al. Incidence of male breast cancer in Scandinavia, 1943–1982. Int J Cancer1989;43:27–31.

  7. Sasco AJ, Lowenfels AB, Pasker-de Jong P. Review article: epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. Int J Cancer1993;53:538–549.

  8. Thomas DB, Jimenez LM, McTiernan A et al. Breast cancer in men: risk factors with hormonal implications. Am J Epidemiol1992;135:734–748.

  9. Goss PE, Reid C, Pintilie M et al. Male breast carcinoma: a review of 229 patients who presented to the Princess Margaret Hospital during 40 years: 1955–1996. Cancer1999;85:629–639.

  10. Yildirim E, Berberoglu U. Male breast cancer: a 22-year experience. Eur J Surg Oncol1998;24:548–552.

  11. Braunstein GD. Gynecomastia. N Engl J Med1993;328:490–495.

  12. Harnden DG, Maclean N, Langlands AO. Carcinoma of the breast and Klinefelter’s syndrome. J Med Genet1971;8:460–461.

  13. Hultborn R, Hanson C, Kopf I et al. Prevalence of Klinefelter’s syndrome in male breast cancer patients. Anticancer Res1997;17:4293–4297.

  14. Casagrande JT, Hanisch R, Pike MC et al. A case-control study of male breast cancer. Cancer Res1988;48:1326–1330.

  15. Rosenblatt KA, Thomas DB, McTiernan A et al. Breast cancer in men: aspects of familial aggregation. J Natl Cancer Inst1991;83:849–854.

  16. Sorensen HT, Friis S, Olsen JH et al. Risk of breast cancer in men with liver cirrhosis. Am J Gastroenterol1998;93:231–233.

  17. Weiderpass E, Ye W, Adami HO et al. Breast cancer risk in male alcoholics in Sweden. Cancer Causes Control2001;12:661–664.

  18. Hsing AW, McLaughlin JK, Cocco P et al. Risk factors for male breast cancer (United States). Cancer Causes Control1998;9:269–275.

  19. Johnson KC, Pan S, Mao Y. Risk factors for male breast cancer in Canada, 1994–1998. Eur J Cancer Prev2002;11:253–263.

  20. Ewertz M, Holmberg L, Tretli S et al. Risk factors for male breast cancer—a case-control study from Scandinavia. Acta Oncol2001;40:467–471.

  21. Rosenblatt KA, Thomas DB, Jimenez LM et al. The relationship between diet and breast cancer in men (United States). Cancer Causes Control1999;10:107–113.

  22. Pollan M, Gustavsson P, Floderus B. Breast cancer, occupation, and exposure to electromagnetic fields among Swedish men. Am J Ind Med2001;39:276–285.

  23. Erren TC. A meta-analysis of epidemiologic studies of electric and magnetic fields and breast cancer in women and men. Bioelectromagnetics2001;(suppl 5):S105–S119.

  24. Sverdlov RS, Barshack I, Bar Sade RB et al. Genetic analyses of male breast cancer in Israel. Genet Test2000;4:313–317.

  25. Struewing JP, Brody LC, Erdos MR et al. Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer. Am J Hum Genet1995;57:1–7.

  26. Ford D, Easton DF, Stratton M et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet1998;62:676–689.

  27. Frank TS, Deffenbaugh AM, Reid JE et al. Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals. J Clin Oncol2002;20:1480–1490.

  28. Basham VM, Lipscombe JM, Ward JM et al. BRCA1 and BRCA2 mutations in a population-based study of male breast cancer. Breast Cancer Res2002;4:R2.

  29. Ottini L, Masala G, D’Amico C et al. BRCA1 and BRCA2 mutation status and tumor characteristics in male breast cancer: a population-based study in Italy. Cancer Res2003;63:342–347.

  30. Friedman LS, Gayther SA, Kurosaki T et al. Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population. Am J Hum Genet1997;60:313–319.

  31. Thorlacius S, Olafsdottir G, Tryggvadottir L et al. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat Genet1996;13:117–119.

  32. Kwiatkowska E, Teresiak M, Filas V et al. BRCA2 mutations and androgen receptor expression as independent predictors of outcome of male breast cancer patients. Clin Cancer Res2003;9:4452–4459.

  33. Wooster R, Mangion J, Eeles R et al. A germline mutation in the androgen receptor gene in two brothers with breast cancer and Reifenstein syndrome. Nat Genet1992;2:132–134.

Learning Objectives

After completing this course, the reader will be able to:

  1. List the risk factors for male breast cancer.

  2. Explain the differences between breast cancer in men and women.

  3. Discuss the importance of adjuvant therapy in male breast cancer.

Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at

One of the rarest cancers in men, breast cancer occurs approximately 100 times less than in women. The lifetime risk of having breast cancer is 1 in 1,000 for men, and incidence has remained relatively stable over the past 30 years. Whereas in the past, the prognosis for men with breast cancer was thought to be worse than for women, recent research has found little difference in outcomes.

But awareness, research, and treatments pose challenges for these patients. Because of disease rarity and recruitment difficulties, studies tend to be small, and recent research shows that breast cancer in men may require sex-specific drug regimens.

BRCA2 Gene Mutations and Risk

In the June 2010 Journal of Medical Genetics , researchers reported that men with a mutated gene for the BRCA2 susceptibility protein carry an 8% lifetime risk of developing breast cancer. The retrospective and prospective analysis of 321 families with pathogenic BRCA2 mutations revealed that in the study, 16 men who were first-degree relatives of known BRCA2 carriers developed breast cancer between the ages of 29 and 79 years. Eight additional cases occurred in second-degree relatives. (Men with a BRCA1 mutation generally do not have an increased risk of development of breast cancer.)

Lead author Gareth Evans, M.D., of St Mary’s Hospital in Manchester, UK, said, “Outside of founder populations, only one in 1,000 people carries the BRCA2 gene mutation, accounting for a little more than 1% of all breast cancer cases. It is a higher percentage for breast cancer in men: Between 5% and 10% of all male breast cancer occurs in men with a BRCA2 gene mutation.” He also notes that men with a BRCA2 mutation have a substantially higher risk of other cancers, including prostate cancer. “The difference with the BRCA2 mutation is that prostate cancers frequently occur in their early 40s, and they tend to be the very aggressive prostate cancers,” Evans said. “Genetic testing where there is a family history is one way forward in terms of men being able to pick up breast cancer early and being aware of prostate risk as well.”

If the patient tests positive for a BRCA2 mutation, Evans advises that the patient have regular screening for prostate-specific antigen. These men should also undergo routine mammography, according to radiologist R. James Brenner, M.D. , of Bay Area Imaging Consultants in Walnut Creek, Calif. He said that male breast tissue is far less dense and that because of lack of lobular development, men usually do not develop benign masses. “Imaging for and diagnosis of male breast cancer is not as technologically challenged,” he said.

Brenner also noted that work still needs to be done to find an easier diagnostic method for asymptomatic patients. “For both men and women, researchers have been looking for a blood test that might alert us to the earliest manifestations of breast cancer,” he said. “Despite repeated pronouncements of optimism, this search remains elusive.” He also said that nipple discharge cytology and attempts to retrieve duct fluid have yet to develop into a reliable approach.

In families with a hereditary history of BRCA2 mutation, testing is an option in conjunction with genetic counseling. “We found that men are less likely to come forward for testing,” Evans said. “About 15% of asymptomatic males will get tested by about 7–8 years after you identify the gene in their family. In women it’s more like 50%–60%.” He speculates that lack of communication may be responsible. In his practice, many men have trouble believing that they can get breast cancer. Also, women are often the family health “gatekeepers” and may be misguided, believing that men are not at risk for the disease or cannot be carriers.

That misconception also persists in the public at large. A 2-year BRCA screening test study started in September 2010, funded by U.S. health insurer Aetna, makes no mention of men, even though its overall aim is to eliminate barriers to tests. Anne Beal, president of the Aetna Foundation, an independent arm of the insurer, said at the time of the announcement, “This study may validate the need for specific strategies to eliminate barriers to these tests—whether they are knowledge based, culturally based, or access based—and help improve health outcomes among high-risk or minority women.”

Treatment Approaches

Men with breast cancer generally follow a protocol similar to that of female breast cancer patients, including a combination of surgery, radiation, chemotherapy, and antihormone therapies. Increasing evidence has found that breast cancer in men may need sex-tailored treatment. One single-center retrospective analysis found that side effects caused more than 20% of men to stop taking tamoxifen, the estrogen receptor antagonist. Of those who ceased taking the medication, 69% did so on their own initiative, according to results in the November 2011 Annals of Oncology .

Primary side effects of tamoxifen in men included weight gain, sexual dysfunction, hot flashes, neurocognitive problems, thromboembolic events, and disturbance of vision. Researchers concluded that although what caused the side effects was unclear, sexual dysfunction could be related to decreased testosterone levels associated with tamoxifen. They also noted that although the study confirmed another retrospective study’s observed discontinuation rates, prospective trials of antihormone treatments for breast cancer in men are still needed.

Despite recent trial setbacks for poly (ADP–ribose) polymerase (PARP) inhibitors for hereditary breast cancers positive for BRCA1 and BRCA2, Evans remains optimistic. “It’s feasible that in the future these drugs could be used to prevent breast cancer in people who have a BRCA2 mutation,” he said. He explained that as the PARP inhibitors target cells that have lost both copies of the BRCA2 gene, they can kill those cells before they become a cancer. “You can envision where someone was actually taking a course of a PARP inhibitor for a week or two every year to clear out all of the bad cells and prevent them eventually going to the breast, prostate, or pancreas, if [the patient is] male.”

Patient Experience

Although awareness of breast cancer in men within hereditary BRCA2 gene mutation families and the general public needs to be improved, patients report that poor understanding by medical personnel continues to be a problem as well. According to research published in October 2011 on Health Talk Online ( , a UK-based health information website led by Oxford University experts) and carried out by Kate Hunt, M.A., M.Sc., the Gender and Health Program Leader at the Medical Research Council’s Public Health Sciences Unit in Glasgow, Scotland, many men reported feeling isolated and embarrassed during their treatment because the service was geared toward women.

Hunt conducted interviews with 33 men from across the UK who had a breast cancer diagnosis; they cited several female-centric experiences during their treatment. These included information pamphlets with female-specific concerns (choice of bra, effect on menstruation, and impact on future pregnancies) being addressed as “Mrs.” rather than “Mr.” when called for an appointment, and pharmacists’ questioning the filling of their tamoxifen prescription. Many men also felt they did not receive enough information on treatment options, receiving less attention from researchers than women. One man reported that he often overheard female patients discussing their participation in trials and the options they were offered, whereas he was offered no such choices in his regimen. The research also found that men were less interested in complementary therapy than women were.

Most research participants acknowledged that breast cancer awareness among women has succeeded, perhaps due partly to the ubiquitous pink ribbon campaign by the Komen Foundation. A few interviewed men suggested adding a flash of blue to promote awareness of breast cancer in men. Hunt suggests taking more care in providing breast cancer information by using sex-neutral terms or at least highlighting that it can occur in men as well. Almost all men interviewed believed that they were the only men treated for breast cancer in their hospital. Some stayed on a breast cancer ward among female patients after surgery, whereas others were placed on a general male surgery ward where staff may lack experience in dealing with breast cancer patients. “It was very difficult for men to meet other men who had the same disease and to find out about their experiences,” Hunt said. In response, experts from added a new section on breast cancer in men, featuring video and text interviews with the research participants.

© Oxford University Press 2012.

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