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    • In the current era nearly all cases of hormone

    2019-06-12

    In the current era, nearly all cases of hormone-receptor positive breast cancer are treated with adjuvant endocrine therapy irrespective of staging, with preference for aromatase inhibitors over tamoxifen because of side effect profile, survival outcome and tumor recurrence rates [4,11]. In our study we found that women who received aromatase inhibitors were younger at the time of hip fracture compared to women who received tamoxifen therapy, similar to findings from Edwards et al. [5] who demonstrated that hip fractures associated with aromatase inhibitors tend to occur at a younger age than otherwise expected. While we cannot exclude the possibility that differences by endocrine therapy reflect changes in breast cancer care over the past two decades (with more recent use of aromatase inhibitors), epidemiologic data demonstrating increased bone loss and fracture risk with aromatase inhibitors [3–5,7,8] also emphasize the need to further examine contemporary fracture risk in women with treated breast cancer. As osteoporosis therapy is currently recommended for patients initiating aromatase inhibitor treatment known to be at high fracture risk [2,7,12,30] and high dose intravenous bisphosphonate therapy remains a primary treatment modality in the setting of skeletal metastases, long term treatment strategies in women with breast cancer should also consider monitoring for rare atypical fractures in the setting of potent antiresorptive therapy. Our study has some limitations. First, the true proportion of pathologic fractures may have been higher than reported since cases of impending fracture (which are generally pathologic) were excluded, bone histopathology was not uniformly available [16], and systematic review of clinical and radiologic findings was not conducted for the entire cohort. In addition, other risk factors for hip fracture, chemotherapeutic exposures and cancer progression [5,12] were not examined, and pharmacologic care outside our health system or prior to 1995 were not available for this study. Finally, our cohort was not large enough to differentiate outcomes by breast cancer subtype and extent of primary disease. Nonetheless, this study represents one of the largest contemporary cohorts of breast cancer survivors in whom progesterone receptor fracture site and subtype have been carefully examined. Importantly, population studies examining hip fracture outcome in younger women with breast cancer should note that a significant proportion of fractures may be pathologic rather than fragility in nature. In addition to pathologic fractures, a small number of diaphyseal femur fractures in bisphosphonate-treated women may be atypical. Finally, with the increasing use of adjuvant aromatase inhibitor and bisphosphonate therapy, future studies should examine long term clinical outcomes associated with optimization of bone health in women with a history of breast cancer.
    Conflict of interest statement
    Acknowledgments This study was supported in part by a grant from the Kaiser Permanente Community Benefit Program. The study sponsor had no involvement in the study design, data collection, analysis and interpretation of data, the writing of the manuscript and the decision to submit the manuscript for publication.
    Introduction In many patients with distant metastatic breast cancer (BC), the skeleton is the site of the most significant tumor burden [1]. In some cases, bone metastases (BM) are relatively silent but many patients, particularly those who have less aggressively growing tumors with a long-term course, develop clinically symptomatic lesions which are not infrequently associated with severe pain. In this situation, radiotherapy and/or surgery might be performed with palliative intention and the primary goals of treatment include prevention and palliation of symptoms, maintenance or improvement of quality of life and prolongation of survival [2–4]. In the literature, there exists a large amount of information on palliative radiotherapy and surgical interventions on BM during the disease course of metastatic BC (overview in: [2,5–7]). However, most of the published studies evaluate only specific therapy options in pre-selected groups of patients, e.g. most of the published studies on palliative radiotherapy focused on the effect of different fractionation regimens and total radiation doses [2]. In doing so, these studies primarily reflect the perspective of one oncological subdiscipline, namely radiation oncology or orthopedic surgery. However, they did not utilize control groups of patients with metastases at the same site who were not radiated or operated, nor take into account how these procedures were embedded in the overall course of distant metastatic disease (DMD).