Oestrogen-progestin therapy increases risk of abnormal mammograms and of larger, advanced stage invasive breast cancers in postmenopausal women

Hinton, Christopher P. MD, FRCS

The Princess Royal Hospital; Telford, UK

Abstracted from:Chlebowski R, Hendrix S, Langer R et al. Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 2003; 289: 3243-3253 .

Sources of funding: This study was funded by the National Heart, Lung and Blood Institute, National Institutes of Health, Department of Health and Human Services.

Correspondence to: Rowan T Chlebowski, Harbor-UCLA Research and Education Institute, Carson Street, Torrance, California, USA. E-mail: [email protected]

Abstract provided by Bazian Ltd, London

Evidence-based Healthcare 8(1):p 43-44, March 2004.

BACKGROUND

The Women's Health Initiative (WHI) randomised controlled trial confirmed that combined hormone therapy (HRT) increases the risk of invasive breast cancer. A comparison of the breast cancers that developed in the combined hormone therapy and placebo groups has not been carried out.

OBJECTIVE

To compare the characteristics of the breast cancers that developed in the HRT and placebo groups of the WHI trial and to determine whether hormone use affected mammography results.

SETTING

Forty clinical centres in USA; enrolment 1993 to 1998, study terminated July 2002.

METHOD

Double-blind randomised controlled trial.

PARTICIPANTS

16,608 postmenopausal women aged 50 to 79 years old. Main exclusion criteria were: prior hysterectomy or breast cancer, or life expectancy less than 3 years. Women already taking hormones underwent a 3-month wash out period prior to baseline testing. Participants received a mammogram and clinical breast examination at baseline; abnormal findings had to be cleared before study entry.

INTERVENTION

Women were randomised to HRT (0.625 mg conjugated equine oestrogen plus 2.5 mg medroxyprogesterone acetate) or matching placebo once daily. Mammography and clinical breast examinations were performed annually. Mean follow-up was 5.6 years; maximum follow-up was 8.6 years.

OUTCOMES

Incidence of breast cancer; characteristics of breast cancers; mammography results.

MAIN RESULTS

HRT significantly increased overall risk of breast cancer, and risk of invasive breast cancer compared with placebo (all breast cancers: 245 cases versus 185 cases, hazard ratio 1.24, 95% CI 1.02 to 1.50; invasive breast cancer 199 cases versus 150 cases, hazard ratio 1.24, 95% CI 1.01 to 1.54). Invasive breast cancers in the HRT group were significantly larger, more likely to be node positive, and diagnosed at more advanced stages than in the placebo group (mean tumour size: 1.7 cm with hormone versus 1.5 cm with placebo, p = 0.04; AR for node positive: 25.9% with HRT versus 15.8%, p = 0.03; AR for diagnosis at the SEER regional/metastatic stage: 25.4% with HRT versus 16.0% with placebo, p = 0.04). There was no significant difference between groups in histological classification (p = 0.89) or morphological grade (p = 0.61) of tumour. HRT significantly increased the risk of having at least one abnormal mammogram compared with placebo (31.5% with HRT versus 21.2% with placebo; p < 0.001).

AUTHORS' CONCLUSIONS

Combined oestrogen-progestin hormone therapy increases the risk of breast cancer in post-menopausal women. Cancers are diagnosed at a more advanced stage, and women are more likely to have abnormal mammograms. Combined hormone therapy may promote breast cancer growth and impede breast cancer detection.

NOTES This study presented subgroup analyses and it is not clear whether they were a priori subgroup analyses. In addition, no adjustment to the level of significance was made to compensate for the multiple analyses performed.