aromatase inhibotor

Analyses Adjusting for Selective Crossover Show Improved Overall Survival With Adjuvant Letrozole Compared With Tamoxifen in the BIG 1-98 Study

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Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. PATIENTS AND METHODS Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. Results Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months. CONCLUSION Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer.

source: JCO

Cancer Therapy Associated Bone Loss: Implications for Hip Fractures in Mid-Life Women with Breast Cancer

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Aromatase inhibitors (AIs) have been recently associated with hip fractures. We present a case series of breast cancer survivors and a systematic review of bone health care in breast cancer.

Experimental Design: We completed clinical assessments and bone density testing (BMD) of hip fractures from January 2005 to December 2008. Prefracture and 12-month functional status was obtained. Systematic review included case reports and review of MEDLINE, PubMed, EMBASE, and Food and Drug Administration Adverse Event Reporting System (FDA AERS) from January 1998 to December 2008 (search terms: breast cancer, bone loss, osteopenia, osteoporosis, malignancy, cancer treatment, menopause, adriamycin, cytoxan, tamoxifen, and AIs).

Results: Median age was 53.5 years; five women had osteopenia, one osteoporosis. Five cases were ER (+), and received surgery, XRT chemotherapy, and anastrozole. Functional decline was noted at 12 months, with difficulty in performing heavy housekeeping, climbing stairs, and shopping. The FDA AERS database included 228 cases of fractures associated with breast cancer therapy; 77/228 (29.4%) were hip or femur fractures. Among mid-life women under the age of 64 years there were 78 fractures; 15/228 (19%) were hip and femur fractures. AIs were the most common drug class associated with fractures (n = 149, 65%).

Conclusions: Cancer treatment induced bone loss results in hip fractures among mid-life women with breast cancer. Hip fractures occur at younger ages and higher BMD than expected for patients in this age group without breast cancer. Hip fractures result in considerable functional decline. Greater awareness of this adverse drug effect is needed.

source: cancer research