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Men’s breast cancer may be linked to infertility – ICR study

The risk of invasive breast cancer in men may be associated with self-reported infertility in the male partner, found research from The Institute of Cancer Research (London), in Breast Cancer Research.

The authors add that the reasons are not clear and more investigation is needed.

Their study, said breast cancer in males was less common than in females and its relation to infertility has only been investigated in small studies to date. Only one small study has suggested a possible association between men fathering children and breast cancer.

The authors interviewed 1,998 males in England and Wales diagnosed with breast cancer, with 112 (5.6%) also self-reporting infertility and 383 (19.2%) having no children.

Co-author Michael Jones and colleagues investigated the potential relationship between self-reported infertility or having had no children and the risk of breast cancer in men, and interviewed 1,998 males (under 80) who were diagnosed with breast cancer between 2005 and 2017, living in England and Wales. They were compared with 1,597 males as a control group, who were not blood relatives: 80 males reported infertility (5.0%) in the control group.

The risk of invasive breast cancer tumours (cancerous cells that spread beyond where they first formed) was significantly associated with male infertility based on 47 individuals with breast cancer (2.6%) compared with 22 controls without cancer but with self-reported infertility (1.4%). The authors did not find any significant associations between the risk of breast cancer and a partner’s infertility or when the source of infertility was not known.

In further investigations, the authors observed a greater number of males with breast cancer (383 males) reported not having any children compared to controls (174 males). However, the authors caution that not having children does not fully reflect male infertility, as males may choose to not have children for a range of cultural and social reasons.

The associated risk of breast cancer with infertility or no children was not significant based on 160 individuals with in situ breast cancer tumours (cancerous cells that do not spread beyond where they first formed) compared to the 1,597 controls.

Jones said: “Our data reveals that there may be an association between male infertility and invasive breast cancer in men.”

The authors conducted further sensitivity analyses to control for alcohol consumption, smoking, family history of breast cancer, and liver disease, in case of potential confounding, but found no strong evidence that these factors affected findings. They did not control for obesity, but did exclude data in some of the analyses from 11 males with Klinefelter syndrome, nine with prior cancer, 29 males who were severely obese and 169 who had testicular diseases. Three individuals who were born female were not included in any of the analyses.

The authors caution that self-reported fertility has the potential for mis-classification, as fertility is a complex process that can include factors from both the male and female members of a couple. Men may not report children outside a marriage or those of whom they may be unaware, or they may have remained childless by choice. The authors propose that validating infertility with medical records, although impractical in this investigation, may reduce recall bias in future investigations.

“The causes of breast cancer in men are largely unknown, partly because it is rare and partly because previous studies have been small,” added Jones. “The evidence in our study suggests the association of infertility and breast cancer should be confirmed with further research and future investigations are needed into the potential underlying factors, such as hormone imbalances.”

Study details

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.

Published in Breast Cancer Research on 17 May 2022

Abstract

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.

 

BCR article – Infertility and risk of breast cancer in men: a national case–control study in England and Wales (Open access)

 

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