Bisphosphonates May Cut Risk of Endometrial Cancer

An analysis of a large number of women suggested that those who use bisphosphonates, a bone medication used to treat osteoporosis and other bone loss diseases, have a reduced risk of endometrial cancer. The results were published in Cancer, a peer-reviewed journal of the American Cancer Society.

Sharon Hensley Alford, PhD, of the department of public health sciences at Henry Ford Health System in Detroit, and colleagues used self-reported questionnaires that were part of the National Cancer Institute’s Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to test the hypothesis that bisphosphonates may mitigate the risk of endometrial cancer.

After accounting for factors such as age, race, history of hormone therapy use, smoking status, and body mass index in the 23,485 women included in the analysis, those who were bisphosphonate users were half as likely to develop endometrial cancer (incidence rate ratio of 0.489). There were 77 cases of endometrial cancer in the group who never used bisphosphonates and 20 in the user group. Sixty-nine and 19 cases in the never-user and user groups, respectively, were type I endometrial tumors.

Ninety-two percent of the women included in the study were white non-Hispanic women, suggesting that the effect of bisphosphonates on African-American and Hispanic women needs to be studied further. Another limit of the study is whether bisphosphonates affect type I and type II endometrial tumors in the same way, since the vast majority of cancer incidences were type I tumors.

“Other studies have shown that bisphosphonates may reduce the risk of certain cancers, but we are the first to show that the risk for endometrial cancer may also be reduced,” said Alford in a statement. “This study suggests that women who need bone strengthening medications and who have increased risk for endometrial cancer may want to choose the nitrogen form of bisphosphonates because this form may reduce the risk of endometrial cancer.”

The study analyzed data only on certain bisphosphonates-those that contain nitrogen, which have been shown to have anticancer properties. These agents are also used as a palliative treatment for patients with bone metastases. There is preclinical evidence that these drugs have anti-tumor effects, including inhibiting proliferation, angiogenesis, and adhesion of tumor cells. In the laboratory, bisphosphonates have also been shown to alter the tumor microenvironment and induce tumor cell death. Bisphosphonates are currently being studied in the clinic as agents that could prevent disease progression or metastasis, but their role as chemopreventive agents has not been well explored. “It is now clear that these drugs, particularly those that contain nitrogen, also affect tumor cells,” wrote the authors.

Endometrial cancer is typically diagnosed in postmenopausal women in their 60s and 70s, at the time of decreasing bone density. It accounts for almost 50% of gynecologic cancers diagnosed in the United States, and is the fourth most common cancer in women.

“Additional studies are needed that include other potential confounders and a larger sample so that type II endometrial cancer could be assessed more confidently. A randomized trial in postmenopausal women that assessed endometrial, breast, and colorectal cancer would be ideal,” concluded the authors.