Oral Bisphosphonate Use Reduces Risk of Postmenopausal Endometrial Cancer


Key Points

  • Oral bisphosphonate use in postmenopausal women was associated with a reduced risk of endometrial cancer.
  • The crude incidence was 8 vs 12 cases/10,000 person years for users vs nonusers.

Bisphosphonate use for treatment or prevention of osteoporosis in postmenopausal women has been associated with a reduced risk of breast cancer, including in a study in the Women’s Health Initiative (WHI) population. In a WHI study reported in the Journal of Clinical Oncology, Newcomb et al found that oral bisphosphonate use was associated with a reduced risk of postmenopausal endometrial cancer.

Study Details

The study involved 89,918 postmenopausal women participating in the WHI. Bisphosphonate use was ascertained from an inventory of regularly used medications at baseline and during follow-up. All women had an intact uterus at study entry. Oral bisphosphonate use increased from 2% at baseline to 10% by year 6 of follow-up. Alendronate accounted for > 90% of bisphosphonate use.

Endometrial Cancer Risk

Over a median follow-up of 12.5 years, 1,123 women were diagnosed with incident invasive endometrial cancer, including 53 bisphosphonate users and 1,070 nonusers. The crude incidence of endometrial cancer was 12 cases per 10,000 person-years among nonusers and 8 and 7 per 10,000 person-years among users of any type of bisphosphonate and alendronate users. In an age-adjusted analysis, the hazard ratio (HR) for cancer associated with bisphosphonate use was 0.76 (P < .01). In a multivariate analysis adjusting for baseline age, 5-year hip fracture probability, body mass index, race, education, smoking status, estrogen-only use, estrogen-progestin use, oral contraceptive use, parity, and mammography, the HR was 0.80 (P = .05) for all bisphosphonate users and 0.77 (P = .03) for alendronate users.

HRs according to the duration of bisphosphonate use were similar; according to duration of < 1, 1 to 3, and > 3 years, HRs were 0.73, 0.75, and 0.77 in age-adjusted analysis and 0.85, 0.81, and 0.76 in multivariate analysis, respectively.

No significant interactions of bisphosphonate effect were observed with body mass index (P = .41), age (P = .21), or hip fracture probability score (P = .83).

The investigators concluded: “In this large prospective cohort of postmenopausal women, bisphosphonate use was associated with a statistically significant reduction in endometrial cancer risk.”

Polly A. Newcomb, PhD, of Fred Hutchinson Cancer Research Center, is the corresponding author of the Journal of Clinical Oncology article.

The Women’s Health Initiative program is supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, and U.S. Department of Health and Human Services. Rowan T. Chlebowski, MD, reported a consultant or advisory role with Novartis, Pfizer, Genentech, Novo Nordisk, and Genomic Health; speakers bureau with Novartis; and travel, accommodations, and expenses with Novartis, Pfizer, Genentech, Novo Nordisk, and Genomic Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.