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


BACKGROUND
clinicaltrials.gov Identifier: NCT00000611.
Chlebowski
Rowan T
RT
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. rchlebowski@gmail.com
Anderson
Garnet
G
Pettinger
Mary
M
Lane
Dorothy
D
Langer
Robert D
RD
Gilligan
Mary Ann
MA
Gillian
Mary Ann
MA
Walsh
Brian W
BW
Chen
Chu
C
McTiernan
Anne
A
D000368:Aged; D001706:Biopsy; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D004967:Estrogens; D004966:Estrogens, Conjugated (USP) / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008327:Mammography; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use*; D008875:Middle Aged; D011372:Progestins / Q000627:therapeutic use*
D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D011372:Progestins; D017258:Medroxyprogesterone Acetate