New research from the US has discovered that women who used bisphosphonates, commonly-prescribed bone-strengthening drugs, had significantly fewer invasive breast cancers than women who did not use them.

The study is the work of lead investigator Dr Rowan Chlebowski, medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed), and colleagues, and the findings are being presented at the 32nd San Antonio Breast Cancer Symposium in Texas this week from 9 – 13 December. The symposium is presented by the CTRC (Cancer Therapy & Research Center), AARC (American Association for Cancer Research), and the Baylor College of Medicine.

“The idea that bisphosphonates could reduce breast cancer incidence is very exciting because there are about 30 million prescriptions for these agents written annually in the US targeting bone health, and more could easily be used to counteract both osteoporosis and breast cancer,” Chlebowski told the media.

For the study, Chlebowski and colleagues re-analyzed data from the Women’s Health Initiative (WHI), a large observational study set up by the National Institutes of Health (NIH) in 1991 to examine the most common causes of death, disability and impaired quality of life in postmenopausal women. The WHI collected information on cardiovascular disease, cancer, and osteoporosis.

In the 150,000-plus cohort of generally healthy postmenopausal women, the researchers found 32 per cent fewer cases of invasive breast cancer among women who used bisphosphonates (mostly alendronate, marketed as Fosamax by Merck), compared to women who did not use such drugs.

What prompted the study were the findings of a report from a breast cancer trial that suggested bisphosphonate zoledronic acid given intravenously every 6 months resulted in fewer cancers in the other breast.

Chlebowski said that:

“It appeared to make bone less hospitable to breast cancer.”

In deciding how to devise the study, the researchers had to find a way to control for bone density, since that in itself is a risk factor for breast cancer. In other words they had to devise a way to control for potential differences between the women prescribed bisphosphonate and those not prescribed bisphosphonate, because those on the bone-strengthening drugs were on it because they had low bone mineral density, which is linked to lower breast cancer incidence.

They found that about 10,000 of the cohort had their bone mineral density analyzed as part of the WHI study, and for the others, including those prescribed bisphosphonates, the researchers used a 10-item hip fracture predictive score to measure bone density.

Thus they were able to correlate the results of bone mineral density tests in the 10,000 who had the tests with the predictive score in order to correct for any potential difference in bone density in women using bisphosphonates compared to those who did not use them.

Thus prepared, Chlebowski and colleagues then studied data on 2,216 women who were using bisphosphonates when they entered the WHI study.

The results showed that:

  • Only 64 of the bisphosphonate users developed breast cancer, and most of the cases, (50 of them), were estrogen-receptor positive.

  • Overall there was an average of 32 per cent fewer breast cancers among bisphosphonate users compared to non-users.

  • There were 30 per cent fewer estrogen-receptor positive cancers and 34 per cent fewer entry-receptor negative cancers among bisphosphonate users, although the latter finding was not statistically significant due to low numbers.

Speculating on what effect bisphosphonates might have to cause fewer breast cancers, Chlebowski said it could be because the drugs discourage blood vessel formation (which tumors rely on to grow), and help the immune system:

“Bisphosphonates reduce angiogenesis and stimulate immune cells responsible for tumor cell surveillance as potential mediators,” explained Chlebowski.

He said we need to study this link in more detail, because “while we currently have several options for reducing receptor positive breast cancers, none are available for receptor negative cancers”.

Other studies presented at the symposium pointed to a similar link between bisphosphonate use and lower breast cancer risk, and a number of breast cancer trials evaluating oral and intravenous uses of the drug are about to report randomized clinical trial evidence on it.

“Oral Bisphosphonate and Breast Cancer: Prospective Results from the Women’s Health Initiative (WHI).”
Principal investigator Rowan Chlebowski.
Abstract number 21, presented at 32nd San Antonio Breast Cancer Symposium, Texas, 9 – 13 December 2009.

Sources: LA BioMed, AACR, NHLBI.

Written by: Catharine Paddock, PhD