Abstract
In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2‐positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.
Highlights
Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes[1]
When analyzing the IHC characteristics, we observed that ER and/or PgR were more commonly expressed in patients with human epidermal growth factor receptor 2 (HER2) status discordance between the early and metastatic disease compared to patients with concordant HER2 status (p < 0.0001 and p = 0.006, for ER and PgR, respectively)
We analyzed data from a historical cohort of 491 HER2‐positive metastatic breast cancer (mBC) patients treated with pertuzumab‐based regimens and/or T‐DM1 according to standard clinical practice
Summary
Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes[1]. Current guidelines suggest repeating the immunohistochemical (IHC) assessment in patients with metastatic spread and at least one secondary lesion amenable to b iopsy[2]. Discordance in human epidermal growth factor receptor 2 (HER2) status between the tumor and metastatic lesions is widely acknowledged, and not yet completely unraveled in their biologic meaning and prognostic r elevance[3,4,5,6,7,8,9,10,11]. Our research question is whether relevant differences exist in long-term outcomes of patients with concordant HER2 status between the primary tumor and its secondary lesion/s compared to patients whose disease revealed HER2-positivity gain at the IHC assessment of metastatic lesions. We sought to identify factors associated with HER2-positivity gain at the IHC reassessment, for which an impact on prognosis may be foreseen
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