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William J. Gradishar, MD

Articles by William J. Gradishar, MD

In addition to the direct effects of primary tumors in bone, bone complications in cancer patients occur from metastasis to bone and through the effects of cancer-related treatments and conditions. Bone is a very common metastatic site for many cancers, including myeloma, melanoma, and breast, prostate, thyroid, lung, bladder, and kidney cancers. Metastatic bone lesions can be osteolytic (bone destruction resulting from increased bone resorption and reduced formation), osteoblastic (increased bone formation), or both.

The use of adjuvant endocrinetherapy in early-stage breastcancer is thought to eradicatemicrometastatic disease that may leadto systemic recurrences. Until relativelyrecently, the standard adjuvantendocrine therapy option was tamoxifen.Data from the Early Breast CancerTrialists’ Collaborative Group(EBCTCG) overview analysis reporteda 50% reduction in the risk of relapseand a 28% reduction in the riskof death in estrogen receptor (ER)-positive patients treated with 5 yearsof tamoxifen.[1] This benefit was observedregardless of menopausal orlymph node status and whether or notpatients were receiving chemotherapy.There was no such benefit documentedin ER-negative cancersreceiving tamoxifen. Tamoxifen hasalso been associated with a 47% reductionin the risk of developing contralateralbreast cancer.[1]

With the advent of aromataseinhibitor use in the adjuvantsetting,[1] and the inceptionof trials examining their usefor breast cancer prevention, it seemsprudent to evaluate what we know todate about the long-term effects of these agents. Unfortunately, unlike selectiveestrogen-receptor modulators(SERMs)-in particular tamoxifen,[2]which has been used for over 15 yearsin patients with early-stage breast cancer-long-term data on the use of aromataseinhibitors are minimal.