Infertility and Risk of Breast Cancer in Men

A National Case-Control Study in England and Wales

Anthony J. Swerdlow; Cydney Bruce; Rosie Cooke; Penny Coulson; Michael E. Jones


Breast Cancer Res. 2022;24(29) 

In This Article

Abstract and Introduction


Purpose: Breast cancer is uncommon in men and its aetiology is largely unknown, reflecting the limited size of studies thus far conducted. In general, number of children fathered has been found a risk factor inconsistently, and infertility not. We therefore investigated in a case–control study, the relation of risk of breast cancer in men to infertility and number of children.

Patients and Methods: We conducted a national case–control study in England and Wales, interviewing 1998 cases incident 2005–17 and 1597 male controls, which included questions on infertility and offspring.

Results: Risk of breast cancer was statistically significantly associated with male-origin infertility (OR = 2.03 (95% confidence interval (CI) 1.18–3.49)) but not if a couple's infertility had been diagnosed as of origin from the female partner (OR = 0.86 (0.51–1.45)). Risk was statistically significantly raised for men who had not fathered any children (OR = 1.50 (95% CI 1.21–1.86)) compared with men who were fathers. These associations were statistically significantly present for invasive tumours but not statistically significant for in situ tumours.

Conclusion: Our data give strong evidence that risk of breast cancer is increased for men who are infertile. The reason is not clear and needs investigation.


Breast cancer is comparatively rare in men, and its aetiology is largely unknown. There are several commonalities with the disease in women, including a genetic component with several specific genes and SNPs known[1] and a relation to anthropometric factors.[2] There is a very high risk in men with Klinefelter syndrome,[3] and this, along with the relation to anthropometrics, suggests that sex hormone-related factors might be involved, as they are in women, and a raised risk of breast cancer has been found in the only cohort analysis able to examine prior oestradiol levels in men who subsequently developed breast cancer.[4] In women, reproductive-related factors are important in breast cancer aetiology,[5] notably a reduced risk in parous women, and although that relates to the hormonal consequences of parity, which could not plausibly apply in men, it nevertheless seems worth investigating whether male fertility relates to male breast cancer risk. Klinefelter syndrome is associated with infertility,[6] and there is some, but not definitive, evidence that testicular abnormalities may also be associated with male breast cancer risk.[2] Infertility is generally defined as the inability to conceive after at least 12 months of regular unprotected sexual intercourse and can be of male origin or female or contributions from both.[7]

Investigation of the relation of male infertility and reproductive history to breast cancer risk has been hampered, however, by the rarity of the tumour. Few studies have investigated infertility[8–10] or reproductive history,[2,11–15] the largest based on 227 cases of whom 7 reported male infertility.[8] A pooled analysis has been published,[2] but is difficult to interpret because the small studies aggregated had very varied case and control selection criteria, and varied also in definitions of infertility. No significant relation to infertility was found, but there was a significant relation to whether the subject had any children. We have conducted a case–control study in England and Wales covering almost 2000 cases nationally incident over a 12.7 year period and present here the results relating to fertility and children.