title: Risk Factors That Increase Risk of Estrogen Receptor-Positive and -Negative Breast Cancer.
abstract: Risk factors may differentially influence development of estrogen receptor (ER)-positive vs -negative breast cancer. We examined associations with strong, prevalent risk factors by ER subtype.
  
  
  
  Of 1 279 443 women age 35 to 74 years participating in the Breast Cancer Surveillance Consortium, 14 969 developed ER-positive and 3617 developed ER-negative invasive breast cancer. We calculated hazard ratios (HRs) using Cox regression and compared ER subtype hazard ratios at representative ages or by menopausal status using Wald tests. All statistical tests were two-sided.
  
  
  
  For women age 40 years, compared with no prior biopsy, ER-positive vs ER-negative HRs were 1.53 (95% CI = 1.30 to 1.81) vs 1.26 (95% CI = 0.90 to 1.76) for nonproliferative disease, 1.63 (95% CI = 1.23 to 2.17) vs 1.41 (95% CI = 0.78 to 2.57) for proliferative disease without atypia, and 4.47 (95% CI = 2.88 to 6.96) vs 0.20 (95% CI = 0.02 to 2.51) for proliferative disease with atypia. Benign disease proliferation risk was stronger for ER-positive than ER-negative cancer for women age 35 years (Wald P = .04), age 40 years (Wald P = .04), and age 50 years (Wald P = .06). Among pre/perimenopausal women, body mass index (BMI) had a stronger association with ER-negative than ER-positive cancer (obese II/III vs. normal weight: HR = 1.52, 95% CI = 1.19 to 1.94; vs 1.21, 95% CI = 1.08 to 1.36). Increasing BMI similarly increased ER-positive and ER-negative cancer risk among postmenopausal hormone users (Wald P = .15) and nonusers (Wald P = .08). Associations with ER subtype varied by race/ethnicity across all ages (P < .001) and by family history of breast cancer and breast density for specific ages.
  
  
  
  Strength of risk factor associations differed by ER subtype. Separate risk models for ER subtypes may improve identification of women for targeted prevention strategies.
authors.affiliation: Affiliations of authors: Departments of Medicine and Epidemiology and Biostatistics (KK, JAT, EZ) and General Internal Medicine Section, Department of Veterans Affairs (KK), University of California, San Francisco, San Francisco, CA; Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, NM (CCG); San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC); Department of Public Health Sciences, University of California, Davis, Davis, CA (DLM); Group Health Research Institute, Group Health Cooperative, Seattle, WA (DLM).
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
authors.affiliation: Affiliations of authors: Departments of Medicine and Epidemiology and Biostatistics (KK, JAT, EZ) and General Internal Medicine Section, Department of Veterans Affairs (KK), University of California, San Francisco, San Francisco, CA; Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, NM (CCG); San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC); Department of Public Health Sciences, University of California, Davis, Davis, CA (DLM); Group Health Research Institute, Group Health Cooperative, Seattle, WA (DLM).
authors.forename: Charlotte C
authors.initials: CC
authors.lastname: Gard
authors.affiliation: Affiliations of authors: Departments of Medicine and Epidemiology and Biostatistics (KK, JAT, EZ) and General Internal Medicine Section, Department of Veterans Affairs (KK), University of California, San Francisco, San Francisco, CA; Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, NM (CCG); San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC); Department of Public Health Sciences, University of California, Davis, Davis, CA (DLM); Group Health Research Institute, Group Health Cooperative, Seattle, WA (DLM).
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Tice
authors.affiliation: Affiliations of authors: Departments of Medicine and Epidemiology and Biostatistics (KK, JAT, EZ) and General Internal Medicine Section, Department of Veterans Affairs (KK), University of California, San Francisco, San Francisco, CA; Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, NM (CCG); San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC); Department of Public Health Sciences, University of California, Davis, Davis, CA (DLM); Group Health Research Institute, Group Health Cooperative, Seattle, WA (DLM).
authors.forename: Elad
authors.initials: E
authors.lastname: Ziv
authors.affiliation: Affiliations of authors: Departments of Medicine and Epidemiology and Biostatistics (KK, JAT, EZ) and General Internal Medicine Section, Department of Veterans Affairs (KK), University of California, San Francisco, San Francisco, CA; Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, NM (CCG); San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC); Department of Public Health Sciences, University of California, Davis, Davis, CA (DLM); Group Health Research Institute, Group Health Cooperative, Seattle, WA (DLM).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.affiliation: Affiliations of authors: Departments of Medicine and Epidemiology and Biostatistics (KK, JAT, EZ) and General Internal Medicine Section, Department of Veterans Affairs (KK), University of California, San Francisco, San Francisco, CA; Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, NM (CCG); San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC); Department of Public Health Sciences, University of California, Davis, Davis, CA (DLM); Group Health Research Institute, Group Health Cooperative, Seattle, WA (DLM).
authors.forename: Diana L
authors.initials: DL
authors.lastname: Miglioretti
mesh_terms: D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data; D000367:Age Factors; D000368:Aged; D015992:Body Mass Index; D000071060:Breast Density; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000032:analysis*; D012307:Risk Factors; D044465:White People / Q000706:statistics & numerical data
chemical_list: D011960:Receptors, Estrogen