Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk

Abstract

Purpose: Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones.

Patients and methods: Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes.

Results: Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men.

Conclusion: Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers.

Fig 1.

Cohort studies contributing biologic samples for endogenous hormone assays in Male Breast Cancer Pooling Project. EPIC, European Prospective Investigation Into Cancer and Nutrition; HPFS, Health Professionals Follow-Up Study; IQR, interquartile range; MEC, Multiethnic Cohort Study of Diet and Cancer; N. CA, northern California; PHS, Physicians' Health Study; PLCO, Prostate, Lung, Colorectal and Ovarian Screening Trial.

Fig 2.

Schematic of sex steroid hormone metabolism. Sex steroid hormones that were quantitated are underlined. (*) Note that only nine are underlined, but 11 assays were conducted; this is because 3-androstanediol glucuronide (3α-diol-G) was quantitated as separate metabolites of 3-androstanediol-3 glucuronide and 3-androstanediol-17 glucuronide. ADT, androsterone; ADT-G, androsterone glucuronide; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone.