ASCO GI Coverage: Women Who Use Bisphosphonates for Osteoporosis Reduce Their Risk of Colorectal Cancer

The risk of colorectal cancer declined by 33% among postmenopausal women taking oral bisphosphonates for osteoporosis. According to a large cohort study, the benefit kicked in after 1 year of treatment and remained steady at about 50% to 60% after 1 year. The findings are consistent with those from a previous analysis showing a 30% lower risk of breast cancer in women taking bisphosphonates, reported Gad Rennert, MD, PhD, at the Gastrointestinal Cancers Symposium.

"The importance of these findings is that the colon is a tumor site that is less hormonally driven compared with breast cancer," said Rennert, an oncologist at Carmel Medical Center in Haifa, Israel. "As a result, there is a better chance that what we are seeing in this study is a true effect of the drug."

A biologic basis exists for a potential chemopreventive effect of bisphosphonates in breast cancer, estimated at 30% in an analysis from the same Israeli study. Rennert said the drugs appear to inhibit the mevalonate pathway involved in isoprenoid biosynthesis, which plays a key role in cancer pathogenesis. Showing a risk-reducing effect in tumor sites other than the breast would suggest a global effect of bisphosphonates on cancer risk.

To assess the impact of bisphosphonate use on colorectal cancer risk, investigators analyzed data from an epidemiologic study of colorectal cancer in northern Israel. They identified 933 women who developed colon cancer between 1998 and 2004 and compared them with 933 matched controls who did not have colorectal cancer.

Overall, any history of bisphosphonate use was associated with a 33% lower risk of colorectal cancer. Analysis of the data by duration of bisphosphonate therapy showed that the beneficial effect on colorectal cancer risk began after 1 year of treatment. Women who used bisphosphonates for less than 1 year had a nonsignificant 10% increase in the hazard ratio (HR) for colorectal cancer. The magnitude of the association between bisphosphonate therapy and its beneficial effect on colorectal cancer jumped dramatically after 1 year of continuous bisphosphonate therapy. The risk of colorectal cancer was 50% among women who used the bonepreserving drugs for 1 year or more, remained steady at 49% with 2 or more years of use, and increased to 61% with 3 or more years of use.

Several other factors were associated with a reduced risk of colorectal cancer, including aspirin use for 3 years or longer, statin use for more than 1 year, and postmenopausal hormone therapy. In a multivariate analysis, bisphosphonate use for 1 year or longer was associated with a 59% reduction in the hazard for colorectal cancer. Rennert said the association between bisphosphonate use and colorectal cancer was similar in the right and left colon and in the rectum (HR, 0.49; HR, 0.50; HR, 0.50).

"This significant negative association is at least as great as the one we observed on breast cancer risk among postmenopausal women using bisphosphonates for osteoporosis," said Rennert. "The strength and consistency of this association warrant evaluation in chemoprevention studies."

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Rennert G, Pinchev M, Rennert HS, Gruber SB. Association of use of bisphosphonates with risk of colorectal cancer. Paper presented at: 2011 Gastrointestinal Cancers Symposium; January 2011; San Francisco, CA.

Published in Oncology & Biotech News. February 2011.