Abstract
We recently found that trastuzumab benefit may be lower in a small subset of early breast cancer (BC) patients (pts) with tumors expressing high levels of both hormonal receptors (HRs), i.e. triple positive (TP). To better investigate the role of HRs in HER2 positive BC, we retrospectively identified 872 TP BC pts treated with adjuvant chemotherapy alone (cohort A-366 pts), or plus trastuzumab (cohort B-506 pts). Relapse-free-survival (RFS) and breast-cancer-specific-survival (BCSS) were evaluated. Trastuzumab improved RFS and BCSS in all the subsets analyzed, but the effect on BCSS in tumors expressing both HRs in >30% of cells (TP30), and even on RFS in tumors with both HRs expressed in >50% of cells (TP50) was not significant. Distinct patterns of relapse were observed in TP50 and no-TP50 tumors, the former showing low and constant risk in the first 5 years, a late increase beyond 5 years and modest trastuzumab effect. Trastuzumab effect tended to disappear in pts whose tumors expressed ER in >50% of cells. Multivariate analysis of RFS confirmed a significant interaction between trastuzumab and ER expression, with benefit confined to pts whose tumors expressed ER in ≤50% of cells.Our data suggest that the pattern of relapse of TP tumors with high HRs is similar to that of “luminal”, HER2 negative tumors, without clear benefit from adjuvant trastuzumab, which remains the standard treatment even in TP tumors. Confirmatory findings on the extent to which quantitative expression of HRs may impact clinical behavior of HER2 positive BC are warranted.
Highlights
25% of breast cancers overexpress the human epidermal growth factor receptor 2 (HER-2) and have an aggressive clinical behaviour [1]
We retrospectively identified 872 consecutive, triple positive” (TP) positive, early breast cancer patients treated in routine clinical practice in nineteen Italian cancer centers between January 1998 and December 2011
We sought to expand our previous observation that in patients with operable HER2-positive breast cancer, high co-expression of both the estrogen receptor (ER) and progesterone receptor (PgR) (“triple-positivity”-TP) could mitigate the effect of trastuzumab administered with adjuvant chemotherapy [13]
Summary
25% of breast cancers overexpress the human epidermal growth factor receptor 2 (HER-2) and have an aggressive clinical behaviour [1]. The use of trastuzumab combined with chemotherapy has dramatically improved prognosis in all stages of HER-2 positive breast cancer [3,4,5]. There has been a general consensus that the HER-2 oncogene, when overexpressed, is the dominant driver of breast cancer biology, regardless of HR status [6], and current guidelines support the use of anti-HER-2 agents combined with chemotherapy in all the disease settings. The subset of “triple positive” (TP: ER/PgR/HER-2 positive) tumors might represent a distinct entity with a favourable prognosis, and the combination of chemotherapy, HER-2 blockade and endocrine treatment, in some instances, might be considered an overtreatment. Only few studies evaluated the degree of HRs expression in HER-2 positive disease, together with its influence on treatment efficacy and prognosis [11, 12] and, to our knowledge, no study has focused on TP treatment outcomes
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