Scientists from the Barbara Ann Karmanos Cancer Institute in Detroit presented preliminary data that shows nitrogen-containing bisphosphonates, therapeutic agents used to promote bone health and inhibit resorption, may cause a slightly poorer survival rate in post-menopausal women with early stage breast cancer who take them for their anti-osteoporosis properties. The findings were announced today at the 2010 American Society of Clinical Oncology Annual Meeting.
Preclinical data suggests that bisphosphonates exhibit anti-tumor activity. Karmanos researchers, led by Zeina Nahleh, M.D., F.A.C.P., co-leader of the Breast Cancer Multidisciplinary Team and assistant professor of Internal Medicine at Karmanos and Wayne State University School of Medicine, conducted a two-year retrospective study that extracted data from the Metropolitan Detroit Cancer Surveillance System, a Surveillance, Epidemiology, and End Results registry.
A total of 696 patients 50 years and older with Stage I, II and III invasive breast cancer, diagnosed between 2000 and 2003, were included in the study. Ninety-seven women, or 14 percent of study participants, used nitrogen-containing bisphosphonates. The difference in overall survival between bisphosphonate users and non-users was not statistically significant at three years, with overall survival equating to 94 percent of bisphosphonate users and 88 percent of non-users.
However, after adjusting for differences between the groups in age, disease stage, hormone receptor status, endocrine therapy and vitamin D and calcium use, there was a marginally significant difference of 0.07 (on a scale of 0.00 to 1.00) in the three-year survival probability rate between users and non-users, favoring bisphosphonate non-users. In other words, what was thought to have anti-tumor properties appeared to be causing a poorer survival rate in bisphosphonate users as compared to non-users.
Dr. Nahleh said that results are preliminary and that more work needs to occur to understand why bisphosphonates may be lowering the survival rates in some female patients.
"This is just an eye-opener for us to await more studies on bisphosphonates and women with nonmetastatic breast cancer," she said. "It's something worth looking at and we still have a lot of work to do on this subject."
Dr. Nahleh mentioned that bisphosphonates are a regularly prescribed treatment for women with metastatic breast cancer, meant to ward off cancer cells from invading the bones. Because of their reported anti-tumor activity, some doctors may be inclined to prescribe them for women with nonmetastatic breast cancer for their possible anti-cancer properties. But this practice should be currently discouraged until the availability of the results from large ongoing prospective trials, according to Dr. Nahleh.
"The reason for our study is we are looking for improved outcomes in women with early stage breast cancer," she said. "We are evaluating the results from this study. But right now, I think we're justified in saying to these nonmetastatic breast cancer patients, let's wait until we get more data before we prescribe bisphosphonates."
There are randomized trials occurring right now to study bisphosphonate use in an adjuvant setting. Dr. Nahleh said the next step is to conduct more clinical and pre-clinical trials on bisphosphonates on nonmetastatic breast cancer patients and understanding the effects of these drugs on the different types of breast cancer.
Dr. Nahleh said that extensive research was undertaken by Ashish Bhargava, M.D., a resident of Internal Medicine at Wayne State University School of Medicine and Kavita Nirmal, M.D., who at the time of the study was serving a fellowship in the Hematology/Oncology Department at Wayne State University School of Medicine. Judith Abrams, Ph.D., director of the Biostatistics Core at Karmanos and professor of Internal Medicine at Wayne State University Medical Center, and John Graff, Ph.D., MS, former epidemiologist at the Karmanos Cancer Institute, also assisted in the study.
"I hope this study will open venues for more confirmatory research to be conducted," she said. "That's the main question that needs to be answered – does nitrogen-containing bisphosphonates cause a lower survival rate in some women with nonmetastatic breast cancer and which group of patients can be affected?"
New vaccine shows potential in preventing recurrence of triple-negative breast cancer