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Oestrogen plus progestogen increased risk of breast cancer in postmenopausal women
  1. Cathy R Kessenich, RN, DSN, ARNP
  1. Department of Nursing, University of Tampa
    Tampa, Florida, USA

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Q In postmenopausal women, does oestrogen plus progestogen hormone therapy increase the risk of abnormal mammographic results and diagnosis of breast cancer?


Embedded ImageDesign:

randomised, placebo controlled trial (Women’s Health Initiative).

Embedded ImageAllocation:


Embedded ImageBlinding:

blinded (clinicians, participants, data collectors, outcome assessors, and monitoring committee).

Embedded ImageFollow up period:

mean 5.6 years.

Embedded ImageSetting:

40 US clinical centres.

Embedded ImagePatients:

16 608 postmenopausal women who were 50–79 years of age (mean age 63 y). Exclusion criteria: previous hysterectomy, breast cancer, or probable survival <3 years.

Embedded ImageInterventions:

1 daily tablet of conjugated equine oestrogen, 0.625 mg, and medroxyprogesterone acetate, 2.5 mg (Prempro, Wyeth Ayerst, Philadelphia, PA, USA) (n = 8506) or placebo (n = 8102).

Embedded ImageOutcomes:

incidence of breast cancer (total, invasive, and in situ) and abnormal mammography results.

Embedded ImagePatient follow up:



Analysis was by intention to treat. Women who received oestrogen plus progestogen had a greater incidence of total and invasive breast cancer than did women who received placebo; in situ breast cancer cases were not increased (table). The increase in invasive breast cancer with oestrogen plus progestogen was seen across almost all risk categories. Invasive breast cancers were larger in the oestrogen plus progestogen group (mean 1.7 cm v 1.5 cm, p = 0.04) and were diagnosed at a more advanced stage (regional or metastatic [compared with local] 25% v 16%, p = 0.04) than in the placebo group. Women who received oestrogen plus progestogen also had a higher proportion of abnormal mammography results. The difference was seen at 1 year (9.4% v 5.4%, p<0.001) and continued throughout the study (total study period 32% v 21%, p<0.001).

Oestrogen plus progestogen (Oest + Prog) v placebo for postmenopausal women*


In postmenopausal women, oestrogen plus progestogen hormone therapy increased cases of total and invasive breast cancer and abnormal mammogram results.


The complex issues surrounding hormone replacement therapy have been escalating over the past decade. Initial results of the Women’s Health Initiative (WHI) trial released in 20021 have served to further complicate the decisions made by prescibers and potential consumers of hormone therapy. The WHI report by Chlebowski et al provides specific details about breast cancer outcomes for the oestrogen plus progestogen and placebo groups. Similar results regarding hormone therapy and breast cancer have been reported in European studies.2,3

It was previously believed that the increased risk of breast cancer with hormone therapy was seen in women with longer term (>5 y) use. These recent results reveal unexpected findings of early development of invasive breast cancers with the use of oestrogen plus progestogen. Additionally, the use of combined hormone therapy resulted in higher rates of mammographic abnormalities, adding to the emotional and economic burden for both patients and providers.

Future reports of the WHI trial results will help to discern the survival outcomes for the 2 groups and may provide insight about the use of oestrogen alone hormone therapy. In the interim, the results of the WHI to date provide a convincing argument against the use of oestrogen plus progestogen. It seems the increased risk of breast cancer and mammographic abnormalities is truly not worth the potential benefit derived from the therapy.



  • A modified version of this abstract appears in ACP Journal Club.

  • For correspondence: Dr R T Chlebowski, Harbor-UCLA Research and Education Institute, Torrance, CA, USA.

  • Sources of funding: National Heart, Lung and Blood Institute and Wyeth-Ayerst Research Laboratories.