title: Reproductive history and oral contraceptive use in relation to risk of triple-negative breast cancer.
abstract: BACKGROUND
  Triple-negative (ie, estrogen receptor [ER], progesterone receptor, and HER2 negative) breast cancer occurs disproportionately among African American women compared with white women and is associated with a worse prognosis than ER-positive (ER+) breast cancer. Hormonally mediated risk factors may be differentially related to risk of triple-negative and ER+ breast cancers.
  
  
  METHODS
  Using data from 155,723 women enrolled in the Women's Health Initiative, we assessed associations between reproductive and menstrual history, breastfeeding, oral contraceptive use, and subtype-specific breast cancer risk. We used Cox regression to evaluate associations with triple-negative (N = 307) and ER+ (N = 2610) breast cancers and used partial likelihood methods to test for differences in subtype-specific hazard ratios (HRs).
  
  
  RESULTS
  Reproductive history was differentially associated with risk of triple-negative and ER+ breast cancers. Nulliparity was associated with decreased risk of triple-negative breast cancer (HR = 0.61, 95% confidence interval [CI] = 0.37 to 0.97) but increased risk of ER+ breast cancer (HR = 1.35, 95% CI = 1.20 to 1.52). Age-adjusted absolute rates of triple-negative breast cancer were 2.71 and 1.54 per 10,000 person-years in parous and nulliparous women, respectively; by comparison, rates of ER+ breast cancer were 21.10 and 28.16 per 10,000 person-years in the same two groups. Among parous women, the number of births was positively associated with risk of triple-negative disease (HR for three births or more vs one birth = 1.46, 95% CI = 0.82 to 2.63) and inversely associated with risk of ER+ disease (HR = 0.88, 95% CI = 0.74 to 1.04). Ages at menarche and menopause were modestly associated with risk of ER+ but not triple-negative breast cancer; breastfeeding and oral contraceptive use were not associated with either subtype.
  
  
  CONCLUSIONS
  The association between parity and breast cancer risk differs appreciably for ER+ and triple-negative breast cancers. These findings require further confirmation because the biological mechanisms underlying these differences are uncertain.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. aphipps@fhcrc.org
authors.forename: Amanda I
authors.initials: AI
authors.lastname: Phipps
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Ross
authors.initials: R
authors.lastname: Prentice
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Lucile L
authors.initials: LL
authors.lastname: Adams-Campbell
authors.forename: Dorothy
authors.initials: D
authors.lastname: Lane
authors.forename: Marcia L
authors.initials: ML
authors.lastname: Stefanick
authors.forename: Mara
authors.initials: M
authors.lastname: Vitolins
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Kabat
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Li
mesh_terms: D001741:Black or African American / Q000706:statistics & numerical data; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001942:Breast Feeding; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000208:ethnology / Q000378:metabolism / Q000517:prevention & control; D003276:Contraceptives, Oral / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008327:Mammography; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D010298:Parity; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D017584:Reproductive History; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000706:statistics & numerical data; D016387:Women's Health
chemical_list: D014408:Biomarkers, Tumor; D003276:Contraceptives, Oral; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone