Bone health history in breast cancer patients on aromatase inhibitors.

Marilyn L Kwan,Lara Sucheston-Campbell,Chi-Chen Hong,Janise M Roh,Joan C Lo,Christine B Ambrosone,Dawn L Hershman,Cecile A Laurent,Malini Chandra,Theresa E Hahn,Charles P Quesenberry,Li Tang,Song Yao,Lawrence H Kushi,Debashis Ghosh

doi:10.1371/journal.pone.0111477

Marilyn L Kwan, Lara Sucheston-Campbell + Show 13 more

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https://doi.org/10.1371/journal.pone.0111477

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Abstract

A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI) users before breast cancer (BC) diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC). Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001). Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.

Highlights

Aromatase inhibitors (AI) have been replacing tamoxifen (TAM) as adjuvant hormonal therapy for postmenopausal women diagnosed with early stage, hormone receptor (HR)-positive breast cancer
Among the initial aromatase inhibitor (AI) users, 11.2% had a prior history of osteoporosis, including 3.5% at 6 years or more before breast cancer diagnosis, and 7.7% within 6 years (Table 1). 16.3% of the patients had a prior history of any fracture, including 7.6% at 6 years or more before cancer diagnosis, and 8.7% within 6 years
In a large contemporary cohort of breast cancer survivors who were initially treated with AIs, we found that 11.2% had a prior history of osteoporosis, 16.3% any fracture, and 4.6% major fracture before breast cancer diagnosis

Summary

Introduction

Aromatase inhibitors (AI) have been replacing tamoxifen (TAM) as adjuvant hormonal therapy for postmenopausal women diagnosed with early stage, hormone receptor (HR)-positive breast cancer. The current third-generation AIs inhibit 96–99% in vivo aromatase enzyme activity [1], thereby decreasing endogenous estrogen levels far below levels from natural menopause [2]. This highly efficient estrogen depletion by AIs benefits breast cancer patients by extending recurrence-free survival superior to TAM [3,4,5]. AIs put patients at high risk of fractures due to the central role of estrogen in maintaining normal bone metabolism [6]. Several expert groups have developed guidelines for evaluating fracture risk in breast cancer patients who are planning to start AI therapy [7,8,9,10], so that the benefits and harms of AIs can be carefully assessed to make an educated decision on choice of hormonal therapy

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