ReviewNew Approaches in the Management of Male Breast Cancer
Introduction
Male breast cancer (MBC) is a rare but important condition that accounts for 0.1% of all male cancers and carries a higher mortality than its more common female equivalent. Comprising 0.6%-1% of all breast cancers, and with a European prevalence of 1/100,000, MBC has a paucity of clinical and epidemiologic studies in the literature; knowledge of important variations in MBC compared with female breast cancer (FBC) is not, therefore, as well understood as it could be. Compared with FBC, MBC tumors tend to express estrogen receptor (ER) and progesterone receptor (PR) more often, have a differing distribution of cellular origin, are affected differently by various environmental risk factors, and have a lower overall survival rate.1, 2 The risk factors for MBC are summarized in Table 1. In addition, the presence of gynecomastia is not considered a risk factor.3 This article summarizes the key risk factors and clinical features of MBC before going on to consider, in detail, the latest evidence for effective management of the condition.
Section snippets
The Diagnostic Pathway
Patients most commonly present with a painless breast lump.4 Rarely, patients may present with axillary lymphadenopathy alone or with Paget disease of the breast.3, 5 Nipple involvement usually occurs earlier in the disease when compared with FBC; typical changes are ulceration, retraction, or discharge.4 As in FBC, triple assessment (clinical examination followed by imaging and biopsy) is the criterion standard when diagnosing MBC. Clinical examination is invaluable, although it must be noted
Surgical Management of the Breast
Most MBC patients are treated with simple mastectomy in contrast to the breast conserving surgery (BCS) techniques, eg, lumpectomy, now popular with FBC. BCS is considered less appropriate in MBC due mainly to the comparative scarcity of breast tissue and more advanced staging at diagnosis; MBC generally has larger tumors and higher rates of chest wall and retroareolar infiltration. Three studies that compared outcomes in patients undergoing BCS vs. mastectomy are summarized in Table 3. From
Surgical Management of the Axilla
Axillary surgery in breast cancer has become less aggressive in a bid to limit common complications such as arm paraesthesia, chronic pain, lymphedema, and impaired shoulder movement. After the success of sentinel node biopsy (SNB) in FBC, the technique was first described in a case of MBC in 1999.50 It has become increasingly popular with studies that yielded sentinel node identification rates of 96%-100%, in which dual techniques of blue dye and radioisotope localization are used.51, 52
Cytotoxic Chemotherapy
Chemotherapy in breast cancer may be cytotoxic or endocrine in its therapeutic target, with adverse effects and outcomes differing between the sexes. Cytotoxic chemotherapy for MBC, in both the adjuvant and neoadjuvant settings, remains a poorly studied field. There is a limited evidence base that suggests that adjuvant chemotherapy reduces rates of relapse in MBC, but currently such regimens are prescribed less frequently in male disease compared with similar FBC patients matched for age and
Endocrine Chemotherapy
Approximately 90% of MBC is ER+, which strongly supports the use of adjuvant hormonal therapy as a cornerstone of treatment just as it is in female disease. The criterion standard is tamoxifen, a selective ER modulator used in both male and female ER+ disease. Tamoxifen effectively reduces recurrence rates and improves survival. No clinical trials support the use of tamoxifen in MBC. Many retrospective studies, however, have found benefit in using the hormonal adjuvant. One study, of 39 MBC
Monoclonal Antibodies
Trastuzumab, a HER2 downregulator, has proved itself a successful member of the treatment arsenal in FBC. Its role in MBC is less clear, however, because the HER2 receptor appears to be overexpressed less frequently compared with FBC.69 By inferring from its success in women, and with one case report that describes its successful use in metastatic MBC, it seems reasonable to offer trastuzumab to men with HER2+ tumors.70
Radiotherapy
Radiotherapy in MBC, as with chemotherapy, has a paucity of data with which to inform the design of effective treatment regimens. The treatment is used routinely in MBC, in contrast to more sparing use in female disease, because the smaller volume of male breast tissue makes achieving comfortable surgical margins a challenge.71 This is reflected in the highly variable rate of local recurrence in male disease.61, 72 Radiotherapy is associated with significant cardiovascular and pulmonary
Managing Metastatic Disease
Hormonal manipulation remains the first-line therapy for metastatic MBC with cytotoxic chemotherapy as second-line therapy. Hormonal therapy was originally performed surgically via orchidectomy, hypophysectomy, or adrenalectomy. Such approaches were effective in 55%-80% of cases but were traumatic and carried their own morbidity.74 Today, the only such surgery still routinely performed is therapeutic gonadal ablation in ER+ metastatic disease. Hormonal manipulation with tamoxifen is as
Prognosis
The age-adjusted incidence of MBC is increasing for reasons that remain unknown. In contrast to the bimodal age distribution in women, and probably due to the absence of any sudden hormonal changes such as those seen at menopause, the unimodal rate of incidence in men does not slow at age 50 years but continues to climb, as seen in Figure 1.10, 77 Mortality in MBC has continued to improve over the past 30 years despite its late presentation.9 Survival is influenced by the presence of
Conclusion
MBC, although rare, carries significant morbidity and mortality, and understanding it more fully remains a useful and urgent goal. Much of the evidence and rationale for treating the disease derives from our experience with FBC, an approach that has yielded significant improvements in outcomes. However, fundamental anatomic and physiological differences between men and women mean that specific male studies are welcome and needed, even though the scarcity of patients makes this difficult.
Disclosure
The authors have stated that they have no conflicts of interest.
References (79)
- et al.
Breast cancer in men
Surg Clin North Am
(1996) - et al.
Male breast cancer
Lancet
(2006) - et al.
Imaging male breast cancer
Clin Radiol
(2011) - et al.
Male breast disease: clinical, mammographic, and ultrasonographic features
Eur J Radiol
(2002) - et al.
Pictorial review: the imaging features of male breast disease
Clin Radiol
(1997) - et al.
Linkage to BRCA2 region in hereditary male breast cancer
Lancet
(1995) - et al.
TL-201 scintigraphy, mammography and ultrasonography in the evaluation of palpable and nonpalpable breast lesions: a correlative study
Eur J Radiol
(1997) - et al.
Male breast cancer
Crit Rev Oncol Hematol
(2010) - et al.
A review of the management of the male breast carcinoma based on an analysis of 420 treated cases
Breast
(1996) - et al.
Status of HER-2 in male and female breast carcinoma
Am J Surg
(2001)