title: 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.
authors.affiliation: Division of Cancer Etiology, Department of Population Sciences, City of Hope Medical Center, Duarte, California 91010, USA.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Ma
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
authors.forename: Jane
authors.initials: J
authors.lastname: Sullivan-Halley
authors.forename: Linda
authors.initials: L
authors.lastname: Weiss
authors.forename: Polly A
authors.initials: PA
authors.lastname: Marchbanks
authors.forename: Robert
authors.initials: R
authors.lastname: Spirtas
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Burkman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Simon
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Brian L
authors.initials: BL
authors.lastname: Strom
authors.forename: Jill A
authors.initials: JA
authors.lastname: McDonald
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000378:metabolism; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010298:Parity; D011247:Pregnancy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D003276:Contraceptives, Oral; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human