Estrogen plus progestin and breast cancer detection by means of mammography and breast biopsy

Arch Intern Med. 2008 Feb 25;168(4):370-7; quiz 345. doi: 10.1001/archinternmed.2007.123.


Background: The effect of combined hormone therapy on breast cancer detection is not established.

Methods: We examined the effect of combined hormone therapy on breast cancer detection in the Women's Health Initiative trial, which randomized 16,608 postmenopausal women to receive conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) or placebo. Mammography and breast examinations were performed at baseline and annually per protocol, with breast biopsies based on clinical findings. The effects of conjugated equine estrogens plus medroxyprogesterone acetate on breast cancer detection was determined throughout 5.6 years of intervention using receiver operating characteristic analyses to evaluate mammography results.

Results: Conjugated equine estrogens plus medroxyprogesterone acetate increased the cumulative frequency of mammograms with abnormalities vs placebo (35.0% vs 23.0%; P < .001), which had less sensitivity for cancer detection and increased cumulative breast biopsy frequency (10.0% vs 6.1%; P < .001). Although breast cancers were significantly increased and were diagnosed at higher stages in the combined hormone group, biopsies in that group less frequently diagnosed cancer (14.8% vs 19.6%; P = .006). After discontinuation of combined hormone therapy, its adverse effect on mammograms modulated but remained significantly different from that of placebo for at least 12 months (P < .001).

Conclusions: Use of conjugated equine estrogens plus medroxyprogesterone acetate for approximately 5 years resulted in more than 1 in 10 and 1 in 25 women having otherwise avoidable mammogram abnormalities and breast biopsies, respectively, and compromised the diagnostic performance of both. This adverse effect on breast cancer detection should be incorporated into risk-benefit discussions with women considering even short-term combined hormone therapy.

Trial registration: Identifier: NCT00000611.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Biopsy
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / pathology*
  • Drug Therapy, Combination
  • Estrogen Replacement Therapy
  • Estrogens
  • Estrogens, Conjugated (USP) / therapeutic use*
  • Female
  • Humans
  • Mammography*
  • Medroxyprogesterone Acetate / therapeutic use*
  • Middle Aged
  • Progestins / therapeutic use*


  • Estrogens
  • Estrogens, Conjugated (USP)
  • Progestins
  • Medroxyprogesterone Acetate

Associated data