Use of four biomarkers to evaluate the risk of breast cancer subtypes in the women's contraceptive and reproductive experiences study

Abstract

Epidemiologic studies suggest that some hormone-related risk factors in breast cancer differentially influence risk for disease subtypes classified by the status of the estrogen and progesterone receptors (ER/PR). However, it remains unclear whether human epidermal growth factor receptor 2 (HER2) or p53 expression status further differentiates these exposure-risk group associations. We evaluated the associations of oral contraceptive (OC) use and reproductive factors with incident invasive breast cancer subtypes among 1,197 population-based cases and 2,015 controls from the Los Angeles County or Detroit components of the Women's Contraceptive and Reproductive Experiences Study. Case-control comparisons by ER/PR/ HER2/p53 status were conducted by multivariable polychotomous unconditional logistic regression methods. We found that OC use was not associated with any breast cancer subtype as defined by ER/PR/ HER2/p53 status, except for a 2.9-fold increased risk of so-called triple-negative tumors (ER-/PR-/HER2+) among women of 45 to 64 years of age who started OC use before age 18. Parity was associated with a decreased risk of luminal A (ER+ or PR+, HER2 -), luminal B (ER+ or PR+/HER2 +), and ER-/PR-/HER2+ tumors. Age at first full-term pregnancy was positively associated with luminal A tumors among older women. Neither of these reproductive factors was associated with triple-negative tumors. Long duration of breast-feeding lowered the risk of triple-negative and luminal A tumors. p53 status did not define further differential risk patterns. Our findings offer evidence of differences in the hormone-related risk factors between triple-negative cancers and other ER/PR/HER2-defined subtypes of breast cancer. ©2010 AACR.