Relationship between hormonal, reproductive, anthropometric, and lifestyle factors and risk of lobular and ductal breast cancer

Abstract

Background. Recent studies report that use of combined estrogen and progestin hormone replacement therapy (CHRT) increases risk of invasive lobular breast carcinomas (ILC), but has a more modest impact on invasive ductal carcinoma (IDC) risk. However, data on CHRT use for long durations and on risks associated with different CHRT regimens are lacking. Further, though there is evidence that ILC is more hormonally responsive than IDC, few studies have evaluated associations between ILC incidence and other hormonally related breast cancer risk factors, including reproductive, anthropometric, and lifestyle characteristics.Methods. A population-based case-control study of women 65--79 years of age was conducted in western Washington State. The responses of 975 women diagnosed with breast cancer during 1997--1999 were compared to those of 1,007 controls. Associations between use of different hormone replacement regimens, and various reproductive, anthropometric, and lifestyle factors, and risks of IDC (n = 656) and ILC (n = 196) were evaluated using polytomous regression.Results. Users of unopposed estrogen, even for ≥25 years, did not have an elevated risk of breast cancer. Ever users of CHRT had elevated risks of lobular, ductal, and breast carcinomas of all histologic types (odds ratio (OR) = 2.6, OR = 1.6, and OR = 1.7, respectively). Five or more years of oral contraceptive use and use of alcohol also increased risk of ILC, but not IDC. Alternatively, earlier age at menarche, later age at menopause, and obesity were more strongly associated with IDC risk.Conclusions. We find that long-term use of CHRT is more strongly associated with breast cancer risk than is ERT use, and that CHRT use increases ILC risk to a greater magnitude than it does IDC risk. Alternatively, certain reproductive and anthropometric factors were associated with elevated risks of IDC, but not ILC. Our results suggest that endogenous hormone levels are more strongly related to IDC risk than to ILC risk, while exogenous hormones are more strongly related to ILC risk than to IDC risk. Given the known heterogeneity of breast cancer, differences in etiologic associations are not unexpected. Identification of risk factors related to different histologic types of breast cancer will likely further our understanding of breast cancer etiology.