Study to investigate gene’s effect on bone loss in breast cancer patients

Women with oestrogen-responsive breast cancer are often prescribed a drug that reduces their oestrogen levels. But because oestrogen is important to bone health, there is widespread concern about how the oestrogen-reducing drugs – called aromatase inhibitors – affect bones.

A study at Washington University School of Medicine in St. Louis will investigate bone loss in women taking aromatase inhibitors, and researchers are calling for interested women to volunteer.Aromatase is an enzyme that transforms testosterone and other androgens into oestrogen. This process represents the major, if not only, source of oestrogen in postmenopausal women. So giving women aromatase inhibitors can result in nearly complete shutdown of oestrogen production, which can have unwanted side effects. “There are reports of an increased incidence of fractures in women on aromatase inhibitors,” says Reina Armamento-Villareal, M.D., assistant professor of medicine in the Division of Bone and Mineral Diseases and a Washington University bone specialist at Barnes-Jewish Hospital. “But interestingly, studies show that women respond differently to these drugs, possibly because of variations in the gene that produces the aromatase enzyme.” This gene is CYP19. Scientists have identified several variations of CYP19 that can result in either increased or decreased aromatase activity. This in turn influences how aromatase inhibitors affect oestrogen levels. The Washington University study will analyse the sequence of the CYP19 gene in volunteers to see which variation they possess. “Our hypothesis is that the use of aromatase inhibitors can be associated with significant bone loss, and the degree of bone loss will be related to the variations of the CYP19 gene,” Villareal says. The data the researchers collect from the study will aid in establishing the appropriate approach to maintaining bone health in women who are given aromatase inhibitors. This study is an example of how physicians hope to use a patient’s genetic code to create personalized treatment. “As more breast cancer patients use these drugs, more may be expected to experience osteoporotic (porous bone) complications,” Villareal says. “We are attempting to address this issue to identify those that would need early intervention to prevent bone loss with aromatase inhibitor therapy.” Postmenopausal women with breast cancer are eligible to participate. The researchers will compare bone loss in women taking aromatase inhibitors to those not using these drugs, so both groups are wanted for the study. The study will not require participants to alter their cancer treatment. Participants will receive free bone density scans and will be tested for blood markers that indicate bone turnover. Each volunteer will be genotyped for CYP19 variants to investigate any link between genetic profile and bone loss. Women interested in taking part in the study or physicians referring patients for the study can call Villareal or Nicola Napoli, M.D., at (314) 454-8437. This study is conducted by Washington University and was approved by the Washington University Human Research Protection Office. (Source: Washington University School of Medicine : June 2007)