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  • We examined pharmacologic exposures among the subset of wome

    2019-05-15

    We examined pharmacologic exposures among the subset of women diagnosed with breast cancer on or after 1995 (N=620) and found that over two thirds (70.8%) received adjuvant endocrine therapy prior to hip or AZD 6244 fracture, including 30.8% who received tamoxifen only, 23.1% who received aromatase inhibitor only, and 16.9% who received both tamoxifen and aromatase inhibitor at some point during the interval between breast cancer diagnosis and subsequent fracture. Compared to women who received only tamoxifen therapy, women receiving any aromatase inhibitors were significantly younger at the time of fracture (77.7±10.6 vs 81.1±9.4 years old, p<0.001). Even after exclusion of pathologic and atypical fractures, there was a trend towards greater receipt of aromatase inhibitor therapy in younger women with fracture (46.7%, 41.3% and 33.4% for ages 50–64, 65–79 and ≥80 years, p=0.04 for trend) but not for receipt of tamoxifen-only therapy (20.0%, 33.5% and 32.6%, respectively). Overall, 35.5% of women received oral bisphosphonates prior to fracture (median duration 1.3 years, interquartile range 0.3–3.9 years), including one third (35.1%) of women with aromatase inhibitor exposure.
    Discussion This study of more than 800 women is one of the largest studies to date examining femur fracture site and subtype among contemporary women with a history of invasive breast cancer. We found that approximately half of all ascertained fractures occurred in the femoral neck, with a slightly smaller proportion in the femoral pertrochanter (increasing proportionately with age as expected) and only 6% of fractures localized to the femoral diaphysis. These distributions were similar to those ascertained for our health plan population of women age 60 years and older [24,27], except for a higher proportion of diaphyseal fractures in women with breast cancer that were more likely to be pathologic. Overall, nearly 1 in 10 fractures were pathologic, with an even greater AZD 6244 proportion of pathologic fractures among younger women age 50–64 years old (50%). We used several algorithms to identify pathologic fracture in this study, including examination of available bone histopathology findings for the entire cohort and clinical/radiologic findings in women with a coded diagnosis of pathologic fracture or metastases to bone. Our study demonstrates that pathologic fractures of the femur remain an important consideration in younger women with breast cancer and may be increasingly relevant in population-based studies examining fragility fracture outcomes in early postmenopausal women with breast cancer. Melton et al. also found that 45% of fractures occurring in premenopausal women with breast cancer were pathologic, in contrast to 12% among postmenopausal women [14]. Others have reported that up to 14% of femoral neck fractures in patients with co-existing cancer (one-third with breast cancer) have histopathologic evidence of bone metastases [28]. Use of ICD-9 diagnosis codes for pathologic hip fracture identified the majority of cases, although pathologic-coded fractures do include a subset of fragility fractures due to osteoporosis where exclusion based solely on ICD-9 codes may underestimate the burden of fractures secondary to osteoporosis [29]. While atypical fractures accounted for only 1% of femur fractures in this cohort, we noted with interest that 16% of diaphyseal fractures demonstrated an atypical fracture pattern, occurring mostly in women <80 years old. Furthermore, all atypical fracture cases occurred in the setting of prior intravenous or oral bisphosphonate therapy. These findings contrast with previously reported data from our health plan, where 48% of diaphyseal fractures (in women age ≥60 years old) demonstrated an atypical pattern, with atypical fractures accounting for more than 1% of hip and femur fractures [27]. These differences are likely attributable to the larger proportion of pathologic fractures among diaphyseal fracture cases in women with breast cancer and potential differences in race/ethnicity and bisphosphonate exposure which also impact atypical fracture risk [27]. Others have found that 17–29% of subtrochanteric and femoral shaft fractures meet the criteria for atypical fractures among older women [19].