title: Risk factors for ductal and lobular breast cancer: results from the nurses' health study.
abstract: BACKGROUND
  Ductal and lobular carcinomas are the two most common types of invasive breast cancer. Whether well-established risk factors are differentially associated with risk on the basis of histologic subtype is not clear. We prospectively investigated the association between a number of hormonal and nonhormonal exposures and risk defined by histologic subtype among 4,655 ductal and 659 lobular cases of postmenopausal breast cancer from the Nurses' Health Study.
  
  
  METHODS
  Multivariate Cox proportional hazards regression stratified by histologic subtype and time period was used to examine the association between risk factors and the incidence of ductal and lobular subtypes. For each exposure, we calculated the P value for heterogeneity using a likelihood ratio test comparing models with separate estimates for the two subtypes versus a single estimate across subtypes.
  
  
  RESULTS
  The associations with age at menarche (P-heterogeneity (het) = 0.03), age at first birth (P-het < 0.001) and postmenopausal hormone use (P-het < 0.001) were more strongly associated with lobular cancers. The associations with age, nulliparity, parity, age at menopause, type of menopause, alcohol intake, adult body mass index (BMI), BMI at age 18, family history of breast cancer and personal history of benign breast disease did not vary by subtype (P-het ≥ 0.08). Results were similar when we restricted the analyses to estrogen receptor-positive and progesterone receptor-positive tumors.
  
  
  CONCLUSIONS
  These data indicate that breast cancer is a heterogeneous disease, and the differential association with a number of risk factors is suggestive of etiologically distinct tumors. Epidemiological analyses should continue to take into account a modifying role of histology.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. nhjok@channing.harvard.edu
authors.forename: Joanne
authors.initials: J
authors.lastname: Kotsopoulos
authors.forename: Wendy Y
authors.initials: WY
authors.lastname: Chen
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Gates
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
mesh_terms: D000328:Adult; D000367:Age Factors; D000428:Alcohol Drinking; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology*; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology*; D018275:Carcinoma, Lobular / Q000453:epidemiology*; D015914:Estrogen Replacement Therapy; D005192:Family Health; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012307:Risk Factors