Risk factors for HR- and HER2-defined breast cancer in Slovenian postmenopausal women

The study aimed to investigate the influence of some generally recognized risk factors for hormone receptor (HR)- and human epidermal growth factor receptor 2 (HER2)-defined breast cancer among Slovenian postmenopausal women.

Eligible women diagnosed with breast cancer were compared with 709 controls of the same age and ethnicity. Immunohistochemistry and FISH analyses were used to classify cases into molecular subtypes: 454 HR(+), 106 HR(-), 81 HER2(+) and 603 HER2(-). Adjusted odds ratios and 95% confidence intervals were estimated using multivariate logistic regression analysis.

Overweight and obese women were at increased risk of HR(+), HER2(-) and of HR(+), HR(-), HER2(-) tumors, respectively. Women who started menstruating at the age of 11 years or earlier were at decreased risk of ER(-)PR(-) tumors. Users of hormone replacement therapy (HRT) were negatively associated with HR(+) and HER2(-) tumors. The inverse effect was most pronounced with the use of estrogen-only HRT, and longer duration of HRT use did not result in a significant change in risk. In contrast, combined HRT decreased the risk of HER2(+) tumors. Having a first-degree relative with breast and/or ovarian cancer increased the risk of HR(+) and HER2(-) tumors.

We conclude that certain breast cancer risk factors may vary by molecular subtypes. According to our results, HRT use may have a greater influence on HR (+) and HER2(-) breast cancers and the risk of HER2-defined breast cancer may differ with respect to the regimen of HRT.