title: New-onset breast tenderness after initiation of estrogen plus progestin therapy and breast cancer risk.
abstract: BACKGROUND
  Estrogen plus progestin therapy increases breast cancer incidence and breast tenderness. Whether breast tenderness during estrogen plus progestin therapy is associated with breast cancer risk is uncertain.
  
  
  METHODS
  We analyzed data from the Women's Health Initiative Estrogen + Progestin Trial, which randomized postmenopausal women with an intact uterus to receive daily conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg (n = 8506), or placebo (n = 8102). At baseline and annually, participants underwent mammography and clinical breast examination. Self-reported breast tenderness was assessed at baseline and at 12 months. The incidence of invasive breast cancer was confirmed by medical record review (mean follow-up of 5.6 years).
  
  
  RESULTS
  Of women without baseline breast tenderness (n = 14,538), significantly more assigned to receive conjugated equine estrogens plus medroxyprogesterone vs placebo experienced new-onset breast tenderness after 12 months (36.1% vs 11.8%, P < .001). Of women in the conjugated equine estrogens plus medroxyprogesterone group, breast cancer risk was significantly higher in those with new-onset breast tenderness compared with those without (hazard ratio, 1.48; 95% confidence interval, 1.08-2.03; P = .02). In the placebo group, breast cancer risk was not significantly associated with new-onset breast tenderness (P = .97).
  
  
  CONCLUSIONS
  New-onset breast tenderness during conjugated equine estrogens plus medroxyprogesterone therapy was associated with increased breast cancer risk. The sensitivity and specificity of the association between breast tenderness and breast cancer were similar in magnitude to those of the Gail model. Trial Registration clinicaltrials.gov Identifier: NCT00000611.
authors.affiliation: Department of Medicine, David Geffen School of Medicine at University of California, UCLA Medicine/GIM, Los Angeles, CA 90024, USA. ccrandall@mednet.ucla.edu
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Crandall
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Anne
authors.initials: A
authors.lastname: McTiernan
authors.forename: Garnet
authors.initials: G
authors.lastname: Anderson
authors.forename: Susan L
authors.initials: SL
authors.lastname: Hendrix
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Cochrane
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
mesh_terms: D000368:Aged; D001940:Breast / Q000187:drug effects*; D001943:Breast Neoplasms / Q000453:epidemiology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced; D017698:Postmenopause; D016016:Proportional Hazards Models; D012680:Sensitivity and Specificity
chemical_list: D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate