Male Breast Cancer

Etiology

When discussing the etiology of breast cancer in. men, one must uncover the potential genetic or environmental risk factors. Being mindful that the majority of males diagnosed with MBC have no identifiable risk other than increasing age (average age of diagnosis of 71) is important.[2] Similar to women, men have a higher risk of breast cancer if they have a first- or second-degree relative with breast cancer. Studies have shown that an affected sibling or parent of either gender may increase the risk of breast cancer in either the males or females in the family. Bevier et al (2012) noted in their study that the relative risk (RR) of breast cancer was similar in either offspring when the father or mother was affected (RR= 1.73 and 1.74, respectively), but the risk was slightly higher in the females when the brother is affected as opposed to when the sister is affected (RR= 2.48 and 1.39, respectively).[3] Also, in addition to a family history of breast cancer, males with a BRCA mutation appear to have an increased risk for breast cancer as well. Although it is rare for a male to have a BRCA mutation, those with a BRCA2 carrier mutation have a 6% increased risk, and BRCA1 has a 4% risk of developing the disease.[4] Other genetic disorders have been implicated in increasing the risk of MBC, including Klinefelter syndrome (47,XXY), Cowden syndrome (PTEN tumor suppressor gene), Li-Fraumeni syndrome (TP53), Lynch syndrome (PALB2 and mismatch repair genes).[2][4]

The alterations in estrogen-to-androgen ratios are important to note when discussing the etiology of male breast cancer. Estrogen, which stimulates ductal development in breasts, has also been implicated as a potential risk factor for MBC, similar to women. Klinefelter syndrome, as previously mentioned, may increase the risk of MBC through excess estrogen stimulation. Other potential triggers have also been identified and include obesity, marijuana use, hepatic dysfunction, thyroid disease, and estrogen-containing medications.[2] Likewise, a decrease in circulating androgens would result in elevations of the estrogen ratios, and this may occur from conditions such as cryptorchidism, orchitis, and orchiectomy.[5]

Lastly, environmental factors have also been implicated in the possibility of increasing the risk of male breast cancer. As with women, previous radiation therapy has been noted as a potential risk factor. Of note, radiotherapy has been used to treat gynecomastia, but these patients have been found to have a 7-fold increase in the risk of MBC.[6] In addition, certain occupations have been found to increase the risk of MBC, including steel and rolling mills, as well as occupations involved with organic solvents such as trichloroethylene.[7]

Epidemiology

Breast cancer in men is a relatively rare malignancy when compared to breast cancer in women, with a known ratio of 1 case in men to 100 in women, and occurs in about 1% of all breast cancers.[8] Breast cancers in men, in general, account for 0.5% of all cancer diagnoses in men, but there has been recent concern about the rising incidence in the past few decades.[8] Studies have facilitated the hypothesis that in addition to obesity and alcohol, dietary factors may be exacerbating the incidence of MBC, but concrete research and evidence regarding specific dietary patterns have yet to be established.[9] Despite these plausible associations, many individuals who are diagnosed with male breast cancer have no identifiable risk factors.[8]

Histopathology

The most common type of breast cancer seen in men is invasive ductal carcinoma, which constitutes approximately 90% of all male breast cancers.[10] Other types implicated are medullary, papilloma, and lobular. Ductal carcinoma in situ is not commonly found due to a lack of awareness and stigmas related to MBC. This then leads to delayed diagnosis and poorer outcomes for the patients. In breast cancer in men, approximately 90% express the estrogen receptor (ER), and 81% express the progesterone receptor.[10] Study results have also found that the expression of these hormone receptors is more prevalent than breast cancer in women.[11] Thus, adjuvant therapy is usually predicated on the inhibition of these receptors, which is discussed further in the treatment and management section.

History and Physical

Men commonly present to the clinic complaining of a painless mass in a unilateral breast. Other potential symptoms include nipple retraction, nipple discharge, ulceration, and pain.[2] Masses in men are typically easier to appreciate than in women due to the smaller breast size, although gynecomastia may mask the condition. Also, when discussing the history of presenting illness, it is vital to discuss the potential family history of breast cancer, the patient’s past medical history, occupation, and whether there has been previous estrogen or radiation exposure.

Evaluation

Similar to breast cancer in women, the diagnosis of MBC is made by a triple assessment, which includes clinical assessment, mammography, ultrasonography, and core biopsy.[10] Mammography is an effective diagnostic method with a sensitivity of 92% and a specificity of 90%; although due to size and volume differences in male breasts, this modality may be limited at times. Given this, ultrasound-guided core biopsy gives the most definitive diagnosis of MBC and is preferred over fine-needle aspiration.[10]

Most male breast cancers are hormone receptor-positive.

Treatment / Management

Treatment and management of male breast cancer typically follow the same rationale as breast cancer in women, which consists of resection followed by adjuvant endocrine therapy, chemotherapy (CT), or radiotherapy.[12] Management is guided by prognostic factors and is further discussed in the oncology section.

• Simple mastectomy is the option for T1 and T2 cancers.
• Radiation therapy is usually offered to men with T3 or higher tumor stage, positive surgical margins, or four or more positive lymph nodes.
• Tamoxifen is recommended as adjuvant therapy for at least 5 years.
• Most metastatic male breast cancers are estrogen receptor-positive, and thus tamoxifen is preferred.

Differential Diagnosis

Common differentials a clinician should be mindful of during the evaluation of male breast cancer are gynecomastia, abscess, lipoma, metastatic disease, and sarcomas, although these are much rarer.[2]

Surgical Oncology

For early-stage disease (T1-T2, N0-N1), simple or modified radical mastectomies that do not involve the additional removal of the pectoralis muscle have been found to be the preferred choice of resection because retrospective studies have not shown mortality or reoccurrence benefit with radical approaches of resections.[13] Axillary or sentinel lymph node biopsies are typically obtained as well to further designate prognostic factors. Furthermore, due to the relatively small volume of breast tissue in men, breast-conserving approaches are rarely entertained.

Radiation Oncology

The rationale and indications for radiotherapy in MBC are similar to those with women which include if the patient underwent breast-conservative resections as well as those with advanced disease (T3 or T4) who underwent a radical mastectomy.[13] Despite these indications, the data regarding the mortality benefit of radiotherapy for MBC is less clear.[2]

Medical Oncology

As described above, is characterized by estrogen receptor (ER) expression, and thus, endocrine therapy is a vital part of management. Tamoxifen is the common choice of treatment, although aromatase inhibitors have been identified as a potential therapy; however, its role as isolated adjuvant therapy is limited.[12] The data is also limited concerning the efficacy of adjuvant CT. Retrospective studies have shown hormonal therapy to be more efficacious for breast cancer in males than CT [2] for advanced disease. Due to the limitations of data, the indications of CT in male breast cancer have been taken from female breast cancer indications and include positive lymph nodes with tumor size greater than 1 cm and negative hormone receptors. Given these indications, oncologists typically select hormonal therapy first, and in the event of failure of this treatment modality, do they consider the role of CT?[12]

Staging

The staging workup regarding male breast cancer is classified similarly to breast cancer in women and consists of the tumor, node, and metastasis (TMN) staging system. Unfortunately, due to the common delayed diagnosis of breast cancer in men, approximately 40% of all breast cancer at the initial diagnosis is found to be stage III or IV disease.[2]

Prognosis

Due to delayed diagnosis commonly found in male breast cancer, the overall 5-year survival is approximately 40% to 65%. When stratified, stage I is 75% to 100%, stage II is 50% to 80%, stage III is 30% to 60%, and stage IV is 20% to 30%.[10] Despite these findings, when matched with various prognostic factors such as age, stage of disease, and grade, the mortality of males with breast cancer has not been found to be significantly greater than in women with breast cancer.[10]