Abstract
PurposeThere are conflicting results on the potential role of HER2-status on the efficacy of aromatase inhibitors (AIs) and tamoxifen (TAM) in patients with hormone receptor (HR)-positive breast cancer (BC). The purpose of this population-based cohort study was to investigate the potential benefit of AIs compared to TAM as adjuvant therapy in postmenopausal BC patients by HER2-status in the era of modern therapy with HER2-blockade.MethodsA population-based cohort study was performed including all postmenopausal women diagnosed with HR-positive BC without distant metastasis between 2007 and 2012 in three healthcare regions in Sweden. We analyzed the breast cancer-specific survival (BCSS) and overall survival (OS) in two distinct cohorts (HER2-negative, HER2-positive) based on the type of endocrine therapy (ET) used. A propensity score matching was performed separately in the HER2-negative and HER2-positive cohorts, respectively.ResultsAfter propensity score matching, 4368 patients with HER2-negative and 214 patients with HER2-positive BC were available for analysis. In the HER2-negative cohort, an improved BCSS [Hazard Ratio (HR): 0.51; 95% confidence interval (CI): 0.34–0.77, p value < 0.001] and a trend toward improved OS (HR: 0.66; 95% CI: 0.41–1.08, p value = 0.093) in favor of AI-based therapy was observed. In the HER2-positive cohort, no statistically significant difference between AI-based ET and TAM was found in terms of either BCSS or OS, although the direction of HR was similar as in the HER2-negative cohort (HR for BCSS: 0.84; 95% CI: 0.14–5.04, p = 0.849; HR for OS: 0.62; 95% CI: 0.10–3.38, p = 0.345).ConclusionOur study results, based on propensity-matched cohorts, did not support any predictive value of HER2-status on endocrine therapy in postmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status.
Highlights
Breast cancer (BC) is a heterogeneous disease composed of various biologic subtypes with distinct behavior
In our study cohort of BC patients treated according to modern strategies, we found that aromatase inhibitors (AIs)-based therapy improves breast cancerspecific survival (BCSS) in the human epidermal growth factor receptor 2 (HER2)-negative BC cohort
Hormone receptor (HR) in the HER2-positive BC cohort is in the same direction as in HER2-negative BC cohort, the magnitude of effect seems to be larger for the HER2-negative cohort
Summary
Breast cancer (BC) is a heterogeneous disease composed of various biologic subtypes with distinct behavior. Hormone receptor (HR)-positive [estrogen (ER) and/or progesterone (PgR) receptor-positive] BC comprises the most common type of BC, whereas amplification or overexpression of the human epidermal growth factor receptor 2 (HER2) oncogene is present in approximately 20% of invasive BC, half of which express HR [1]. The cornerstone of adjuvant treatment in HR-positive BC is the endocrine therapy (ET) which has resulted in improved survival [2, 3]. In patients with HER2-positive invasive BC, HER2-directed therapy has altered the natural history of this aggressive subtype resulting in improved survival in all treatment settings [5, 6]. Patients with HR+/HER2 + BC are treated with both ET and HER2-directed therapy in adjuvant setting
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