Betty A. Mincey

Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer

PURPOSE Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. PATIENTS AND METHODS Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. RESULTS A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. CONCLUSION Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.

Prevention and Treatment of Osteoporosis in Women With Breast Cancer

Women who have had breast cancer may be at higher risk for osteoporosis than other women. First, they are more likely to undergo early menopause, due to chemotherapy-induced ovarian failure or oopherectomy. In addition, chemotherapy may have a direct adverse effect on bone mineral density (BMD), and osteoclastic activity may increase from the breast cancer itself. While estrogen therapy is considered standard for the prevention and treatment of osteoporosis, use of estrogen in women with a history of breast cancer is usually contraindicated. The approach to osteoporosis in women with breast cancer is also affected by the use of tamoxifen in many, as this drug appears to have opposite effects on BMD in premenopausal and postmenopausal women. We have reviewed therapeutic alternatives for the prevention and treatment of osteoporosis, focusing on patients with a history of breast cancer. Alendronate and raloxifene are currently approved in the United States for the prevention of osteoporosis; alendronate, raloxifene, and calcitonin are approved for treatment. Alendronate has the greatest positive effect on BMD and reduces the incidence of vertebral and nonvertebral fractures. Raloxifene and calcitonin appear to reduce the incidence of vertebral fractures; their effects on the incidence of nonvertebral fractures are not yet proven. Although no published studies specifically address the use of these approved agents for osteoporosis in women with breast cancer, understanding their relative effects on BMD in postmenopausal women in general will facilitate therapy selection in this population. Postmenopausal women with a history of breast cancer should undergo bone mineral analysis. Normal results and absence of other risk factors ensure that calcium and vitamin D intake are adequate. If osteopenia or other risk factors are present, preventive therapy with alendronate or raloxifene should be considered. For osteoporosis, treatment with alendronate should be strongly considered. Raloxifene and calcitonin are alternatives when alendronate is contraindicated. Further studies are needed to evaluate the optimal timing of initial bone mineral analysis in premenopausal women after breast cancer diagnosis and to determine the value of preventive treatment in women scheduled to undergo chemotherapy.

Advances in Screening, Diagnosis, and Treatment of Breast Cancer

Breast cancer is the most common cancer in women in the United States; this year, approximately 215,900 new cases will be diagnosed. Mammography remains the cornerstone of screening, with technologies such as ultrasonography and magnetic resonance imaging having an increasingly defined role. Improved risk assessment and prevention strategies have been implemented, and current research in these areas includes better identification of patients at risk, the use of aromatase inhibitors and other agents to reduce risk, and the use of surrogate markers. Breast cancer staging has been optimized recently; also, local management of breast cancer, adjuvant systemic therapies, and treatment of patients with advanced disease have been evolving. Advances in screening, diagnosis, and treatment of breast cancer continue to influence our approach to patients with this disease. Many improvements have been made as well in supportive care, including increased tolerability of therapy and notable amelioration of disease symptoms.

Predicting BRCA1 and BRCA2 gene mutation carriers: comparison of LAMBDA, BRCAPRO, Myriad II, and modified Couch models

ContextModels have been developed to predict the probability that a person carries a detectable germline mutation in the BRCA1 or BRCA2 genes. Their relative performance in a clinical setting is unclear.ObjectiveTo compare the performance characteristics of four BRCA1/BRCA2 gene mutation prediction models: LAMBDA, based on a checklist and scores developed from data on Ashkenazi Jewish (AJ) women; BRCAPRO, a Bayesian computer program; modified Couch tables based on regression analyses; and Myriad II tables collated by Myriad Genetics Laboratories.Design and settingFamily cancer history data were analyzed from 200 probands from the Mayo Clinic Familial Cancer Program, in a multispecialty tertiary care group practice. All probands had clinical testing for BRCA1 and BRCA2 mutations conducted in a single laboratory.Main outcomes measuresFor each model, performance was assessed by the area under the receiver operator characteristic curve (ROC) and by tests of accuracy and dispersion. Cases “missed” by one or more models (model predicted less than 10% probability of mutation when a mutation was actually found) were compared across models.ResultsAll models gave similar areas under the ROC curve of 0.71 to 0.76. All models except LAMBDA substantially under-predicted the numbers of carriers. All models were too dispersed.ConclusionsIn terms of ranking, all prediction models performed reasonably well with similar performance characteristics. Model predictions were widely discrepant for some families. Review of cancer family histories by an experienced clinician continues to be vital to ensure that critical elements are not missed and that the most appropriate risk prediction figures are provided.

The management of bone loss in patients with breast or prostate cancer.

Osteoporosis is a disease that is associated with significant morbidity and mortality, much of which can be prevented with available therapy. The risk for osteoporosis is increased in individuals with some types of cancer, especially in women with breast cancer and men with prostate cancer. This is caused by several factors, including premature ovarian failure and systemic antihormonal therapy in women, androgen ablation therapy in men, and potential direct effects of chemotherapy and of cancer on bone metabolism. With continual increases in the incidence of breast cancer, earlier detection and treatment, and improvements in survival for both patients with breast and prostate cancer, the importance of appropriate screening for and management of osteoporosis is evident. We review the evidence supporting an increased risk for development of osteoporosis in individuals with breast or prostate cancer, and strategies for prevention and treatment of osteoporosis in these patients.