ReviewMale breast cancer is not congruent with the female disease
Introduction
Because of the relative rarity of male breast cancer (MBC), which comprises <1% of western cases, for men with the disease it has been accepted that trial results derived from its big sister should form the basis for treatment. In the absence of national and international randomised trials for male breast cancer this appears superficially to be an appropriate response. Closer examination of available data suggests that aspects of aetiology and treatment of MBC do not fit the simplistic model that men usually have endocrine sensitive tumours which behave like those in postmenopausal women.
At a microscopic level the major difference between FBC and MBC is the almost total lack of invasive lobular cancers in the latter group since lobular differentiation is an unusual event in males. These very rare cases of invasive lobular cancer may have Klinefelter’s syndrome (Sanchez et al., 1986), be taking estrogens as transsexuals (Burcombe et al., 2003) or prostate cancer sufferers (Dore et al., 1982) but predominantly have no known endocrine risk factor (Spencer and Shutter, 2009). One major obstacle to the molecular investigation of MBC is the absence of any human MBC cell line. Such a resource would greatly improve our understanding of this disease.
Section snippets
Endocrine
Most females and males with breast cancer have none of the recognised risk factors, indicating the gaps in our knowledge of the epidemiology of this disease. For a few men, testicular damage, whether from mumps orchitis, high ambient working temperature, use of estrogens or undescended testes increases risk of MBC (Fentiman and Fourquet, 2006). Despite this, in a case-control study of 75 MBC cases, before starting treatment and 75 neighbourhood controls no consistent differences were identified
Molecular profile of MBC
Wang-Rodriguez et al. (2002) examined expression estrogen receptor (ER), progesterone receptor (PR), MiB1 (Ki67), Her-2/neu (c-erbB2), and in 65 MBC cases and compared outcomes with female breast cancers (Wang-Rodriguez et al., 2002). Males had a significantly worse prognosis and this was predominantly due to tumour size and lymph node status, the latter being the most significant prognostic variable. ER, PR and MiB1 were of limited prognostic value.
Ge et al. (2009) analysed tumours from 42 MBC
Cell cycle proteins
Kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 negatively regulate cell cycle progression by stopping the passage of cycling cells from G1 to S phase through G1 cyclin-dependent kinase activation. Curigliano et al. (2002) examined the immunohistochemical expression of p21Waf1 and p27Kip1 protein in 27 MBC and 101 FBC using immunohistochemistry (Curigliano et al., 2002). There was a statistically significant difference in the immunostaining of tumours from male patients compared with
Chemotherapy
Giordano et al. (2005) reported results of systemic therapy In a large series of 135 patients with non-metastatic MBC (Giordano et al., 2005). There were 32 (84%) who received adjuvant chemotherapy and 10-year overall survival rates were 75% for node negative cases and 43% for node-positive males. There was a non-significant reduction in mortality for those with node-positive disease who received adjuvant chemotherapy but significantly improved survival in those given adjuvant hormonal therapy
Endocrine therapy
Systemic endocrine therapy has been very widely used for FBC as adjuvant, neoadjuvant and preventive treatment. The current consensus is that in an adjuvant or neoadjuvant role, tamoxifen should be used in premenopausal women and an aromatase inhibitor in the postmenopausal (Untch et al., 2013). The latter is based on results of randomised controlled trials (RCTs) that have shown the superiority of anastrozole (Cuzick et al., 2010), letrozole (Ingle et al., 2008) and exemestane (van de Velde et
Conclusions
There are substantial differences in the aetiology of MBC and FBC with the former arising more frequently as a result of BRCA2 mutations with differential effects of single nucleotide polymorphisms (SNPs) by gender. Furthermore, in MBC the miRNA expression signature differs as a result of under-expressed miRNAs. The molecular profile shows are major gender differences with luminal A being the predominant subtype in MBC which is rarely of basal cell types and never HER2 enriched. Cell cycle
Conflict of interest
None.
Acknowledgement
I thank Dr. Nick Orr for his very helpful comments on the manuscript.
Ian Fentiman is Emeritus Professor of Surgical Oncology at GKT School of Medicine, He was appointed Consultant Surgeon at Guy’s Hospital in 1982 and has published over 340 peer-reviewed articles and is author of 7 books. At present he is writing a book on male breast cancer.
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Ian Fentiman is Emeritus Professor of Surgical Oncology at GKT School of Medicine, He was appointed Consultant Surgeon at Guy’s Hospital in 1982 and has published over 340 peer-reviewed articles and is author of 7 books. At present he is writing a book on male breast cancer.