Incidence, Physiology, Treatment and Psychosocial Effects of Male Breast Cancer

Introduction

This essay outlines the incidence, physiology, treatment and psychosocial effects of male breast cancer. The evidence indicating possible causes is subject to critical appraisal and gaps in current research evidence are identified. The key presenting features of male breast cancer are described, and treatment options are briefly summarised. The existing evidence investigating the psychosocial effects of male breast cancer is discussed, identifying specific issues that affect men such as the stigmatisation of experiencing a cancer normally associated with women. A conclusion summarises the salient points raised.

Breast cancer is a rare disease in men and not included in the top twenty cancers responsible for death. Only 1 in 840 men in the UK will experience breast cancer, 55% of them aged over 75. This is reflected by low death rates in men due to the disease; in 2014 male breast cancer (MBC) caused 75 deaths (Cancer Research UK (CRUK), 2017). Macmillan (2018a) report that 10% of MBC arises from inheritance of the BRCA1 or BRCA 2 genes. When combined with a family history of first degree relatives who have experienced breast cancer, male carriers of either of these genes have a moderate risk of developing breast cancer (West of Scotland Cancer Genetics Service (WoSCGS), 2015; Ruddy and Winer, 2013).

The occurrence of breast cancer in men compared to women differs, developing 8-10 years later in men (Fentiman et al., 2006; 2009). The association of MBC with older age may mean that reported mortality due to breast cancer, as distinct from other age-related comorbidities, may be underestimated. Furthermore, Spiers and Shaaban (2010) note that, although in western countries breast cancer rates appear to be declining, the statistics quoted refer only to female breast cancer. These authors compared the incidence of 350 current MBC diagnoses annually in the UK, with figures reported in the late 1970’s and the start of the decade. They found an increasing rate of MBC incidence in the UK comparable to that observed in the United States by Stang and Thomssen (2008). The above discussion raises the question of why male breast cancer incidence appears to be increasing in the UK?

For non BRCA 1 or 2 carriers, age is a significant risk factor for the development of MBC (Cutuli et al., 2010; Fentiman 2009). Therefore, as the proportion of people in the UK classed as old or very old continues to rise (Office of National Statistics (ONS), 2015) it could be argued that a comparable rise in the incidence of MBC can be expected. Brinton et al. (2015) investigated additional risk factors and concluded that, out of 101 MBC sufferers and 217 controls, MBC risk was increased by levels of endogenous oestradiol, although no association was found with circulating androgens. Interestingly, the risk of MBC conferred by high circulating endogenous oestradiol was consistent with that associated with postmenopausal female breast cancer, reported by Kaaks et al. (2014), Dallal et al. (2014), Falk et al. (2013) and others. Brinton et al. (2015) controlled for variables that may confer risk of MBC such as cigarette smoking but did not control for known risk factors that include BRCA 1/ 2 status, previous history of gynecomastia and diagnosis of Klinefelter syndrome.

These are significant omissions that undermine the reliability of Brinton et al.’s (2015) findings. Sufferers of Klinefelter syndrome, for example, have a high ratio of circulating oestrogens compared to androgens (Weiss et al., 2005). Given that, according to the Eunice Kennedy Shriver National Institute of Child Health and Human Development, 2016), the incidence of this condition affects 1 in 500 males, (which is higher than the incidence of MBC) it is reasonable to argue that the risk factor that contributed to MBC in Brinton at al.’s (2015) study could be attributed to this condition, and not high circulating oestradiol levels with no influence from androgens, as suggested.

Fentiman (2009) summarises research that has associated working with hydrocarbons or in hot environments with MBC. Other studies have examined if the trend towards increased Body Mass Index (BMI) observed in populations of western countries such as the US and UK may be linked to the incidence of MBC. Brinton et al., (2008), for example, found that a BMI of more than 30 conferred a risk of MBC, but this study was based upon a small sample size and thus provided limited statistical power to substantiate the authors’ findings. A case-controlled study of 156 men diagnosed with MBC conducted by Ewertz et al., 2001 found no significant associations with parity and age at first childbirth, which is unsurprising given the gender of their sample population. These authors associated the risk of MBC with obesity and diabetes which is not supported by consensual research demonstrating that this link is unsubstantiated (Giovannucci, et al., 2010). Furthermore, Ewertz et al. found no consistent pattern in the association between cigarette smoking and MBC, which is challenged by later studies of female breast cancer. These include Dossus et al. (2013), Xue et al. (2011), Luo et al. (2011) and McCarty et al. (2009).

Therefore, it is difficult to ascertain why MBC incidence appears to be increasing because there is a lack of quality data specifically addressing this question. Nevertheless, the fact that the risk factors associated with MBC are not fully understood indicates a need for further research. This reflects Giordano’s (2005) statement that male breast cancer is an ‘orphan’ disease. Giordano further makes the point that, due to the rarity of the condition, it is not possible to obtain data from prospective randomised controlled trials. Although this type of research has the rigour deemed by some funding councils such as the Medical Research Council (MRC, 2018) to convey quality, this is contentious. Mårtensson, et al. (2016), for example, challenge the linear hierarchy of evidence (described by Bettany-Saltikov, 2012) that is used to judge the quality of research. Research funding councils may need to embrace the concepts presented by Mårtensson to justify alternative approaches to investigating the causes of MBC and the most effective treatments.

MBC frequently presents as a painless sub areolar lump. This arises from tumour cells within the mammary ductal tissue (Ngoo et al., 2009, Jamal et al., 2006). Men with breast cancer may also experience nipple retraction, discharge from the nipple and/ or changes in in the appearance and texture of the skin in the breast and nipple area (Mayo Clinic 2015; Giordano, 2005). Breast tumours are classified according to European Society of Medical Oncology (ESMO) notation (Senkus et al., 2015).  Macmillan (2018b) report that 80-90% of MBC is ductal carcinoma classified by the ESMO as molecular subtype ‘luminal A’. According to Fan et al. (2006), luminal A tumours account for 30-70% of male and female breast cancers. Luminal A tumours generally have a better prognosis than other molecular subtypes that include Luminal B, triple receptor negative and Human Epidermal Growth Factor (HER) type 2 negative tumour cells (Voduc et al., 2010; Carey et al., 2014; Arvold et al., 2010). Although HER positive tumours are receptive to treatment using monoclonal antibody therapy (trastuzumab), they are not generally associated with MBC (Macmillan, 2018c).

Treatment options for MBC are contingent upon the stage of the tumour, its molecular subtype, hormone receptor status (determined by histopathology), the age of the man, his general health and BRCA 1 or 2 status (Senkus et al., 2015; Macmillan, 2018b). Typically, men receive surgery comprising either a lumpectomy to remove the tumour and surrounding tissue or a mastectomy that removes the whole breast. Axillary lymph nodes are removed if the tumour has invaded these glands. To prevent disease re-occurrence, radiotherapy, chemotherapy and/ or endocrine therapy using synthetic hormones such as tamoxifen (for oestrogen receptor positive tumours) are offered (Macmillan, 2018d).

The psychosocial impact of MBC is another under researched area. Men who carry the BRCA 1 or 2 gene, and risk passing this to their children are likely to experience anxiety and feel stigmatised (Strømsvik et al., 2010). France et al. (2000) highlighted the comparison between men with MBC and women with breast cancer in their development of body image problems arising from mastectomy. According to France et al., this may lead to men feeling reluctant to expose their chests or wear clothing that indicates their mastectomy. Kipling et al. (2014) and Andrykowski (2011) suggest that physical problems such as weight gain and diabetes may arise from social isolation that prevents men engaging in activities such as sport, as a result of surgery.

Ruddy and Winer (2013) highlight the different coping strategies used by men with breast cancer, compared to women with the disease. Women are more likely to seek support, whereas men are more likely to use maladaptive coping strategies that include avoidance. However, despite the rarity of MBC, support is available from The Male Breast Cancer Coalition (2018). Men who have the BRCA 1 or 2 gene and have a 50% chance of passing this to their daughters should have the opportunity for genetic counselling, which they are eligible to receive according to National Institute for Health and Care Excellence (NICE) guidelines (NICE, 2013).

Conclusion

In summary, there is little evidence to indicate why the rate of male breast cancer, which affects only 1 in 840 men may be increasing, and only a small amount of research has addressed MBC. Men who feel stigmatised by experiencing a cancer normally associated with women may suffer from social isolation and associated psychological and physical morbidities. To address the lack of evidence, funding bodies need to recognise the value of other types of research beyond RCT’s which require large sample populations to achieve statistical rigor. However, the stigma men may feel through experiencing MBC may only be reduced by greater public awareness that breast cancer does not only affect women. This may have the additional benefit of enhancing men’s awareness of their breasts and being alert to any changes that could indicate MBC, enabling earlier detection and improved outcomes.

References

Andrykowski M. A., 2011. Physical and mental health status and health behaviors in male breast cancer survivors: a national, population-based, case-control study. Psychooncology 21(9) pp. 927–934.

Arvold, N.D., Taghian, A.G., Niemierko, A., Raad, R.F.A., Sreedhara, M., Nguyen, P.L., Bellon, J.R., Wong, J.S., Smith, B.L. and Harris, J.R., 2011. Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. Journal of Clinical Oncology, 29(29), pp.3885-3891.

Bettany-Saltikov, J., 2012. How to do a systematic literature review in nursing: a step-by-step guide. McGraw-Hill Education, Basingstoke (UK).

Brinton, L.A., Key, T.J., Kolonel, L.N., Michels, K.B., Sesso, H.D., Ursin, G., Van Den Eeden, S.K., Wood, S.N., Falk, R.T., Parisi, D. and Guillemette, C., 2015. Prediagnostic sex steroid hormones in relation to male breast cancer risk. Journal of Clinical Oncology, 33(18), pp.2041-1250.