title: Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina Breast Cancer Study: a case-control study.
abstract: Young-onset breast cancer (<40 years) is associated with worse prognosis and higher mortality. Breast cancer risk factors may contribute to distinct tumor biology and distinct age at onset, but understanding of these relationships has been hampered by limited representation of young women in epidemiologic studies and may be confounded by menopausal status.
  
  
  
  We examined tumor characteristics and epidemiologic risk factors associated with premenopausal women's and young women's breast cancer in phases I-III of the Carolina Breast Cancer Study (5309 cases, 2022 control subjects). Unconditional logistic regression was used to assess heterogeneity by age (<40 vs. ≥40 years) and menopausal status.
  
  
  
  In both premenopausal and postmenopausal strata, younger women had more aggressive disease, including higher stage, hormone receptor-negative, disease as well as increased frequency of basal-like subtypes, lymph node positivity, and larger tumors. Higher waist-to-hip ratio was associated with reduced breast cancer risk among young women but with elevated risk among older women. Parity was associated with increased risk among young women and reduced risk among older women, while breastfeeding was more strongly protective for young women. Longer time since last birth was protective for older women but not for young women. In comparison, when we stratified by age, menopausal status was not associated with distinct risk factor or tumor characteristic profiles, except for progesterone receptor status, which was more commonly positive among premenopausal women.
  
  
  
  Age is a key predictor of breast cancer biologic and etiologic heterogeneity and may be a stronger determinant of heterogeneity than menopausal status. Young women's breast cancer appears to be etiologically and biologically distinct from that among older women.
authors: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
authors: Lynn
authors: L
authors: Chollet-Hinton
authors: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.|Division of Hematology-Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors: Carey K
authors: CK
authors: Anders
authors: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
authors: Chiu-Kit
authors: CK
authors: Tse
authors: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors: Mary Beth
authors: MB
authors: Bell
authors: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.|Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA.|Department of Sociology, University of North Carolina, Chapel Hill, NC, USA.
authors: Yang Claire
authors: YC
authors: Yang
authors: Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors: Lisa A
authors: LA
authors: Carey
authors: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors: Andrew F
authors: AF
authors: Olshan
authors: Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. troester@unc.edu.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. troester@unc.edu.|Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA. troester@unc.edu.
authors: Melissa A
authors: MA
authors: Troester
mesh_terms: D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009367:Neoplasm Staging; D009657:North Carolina / Q000453:epidemiology / Q000208:ethnology; D010298:Parity; D011159:Population Surveillance; D011247:Pregnancy; D012307:Risk Factors
keywords: Age; Breast cancer; Epidemiology; Risk factors; Tumor characteristics