Triple positive breast cancer: A distinct subtype?

Abstract

Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets.

From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer?

“…In HR+ HER2+ patients treated with tamoxifen, poor clinical outcome correlates with a high expression level of HER2 and/or HER1 in the ER+/PR− subgroup but not the ER+/PR+ group, suggesting the PgR negativity is an indicator of the dominant role of HER1/HER2 pathway [25, 39]. On the other hand, Vici et al propose that ER+ PgR+ HER2+ tumors with high expression of HRs behave similarly to the HR+ HER2− subtype in the clinic, suggesting that certain HR+ HER2+ patients may be over-treated by the standard treatment [136]. Therefore, the expression levels of ER and/or PgR may serve as predictive biomarkers to guide the choice of treatment regimens and predict prognosis in HR+ HER2+ breast cancers.…”

Gene regulatory pattern analysis reveals essential role of core transcriptional factors’ activation in triple-negative breast cancer

“…According to the evaluation of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2/ERBB2/Neu), breast cancers are routinely divided into hormone receptor positive, HER-2/Neu amplified, and triple-negative breast cancer (TNBC) subtypes [2–4]. TNBC is particularly aggressive, thus often associated with relapse and the worst prognosis [3]. Due to a lack of appropriate molecular targets, TNBC patients could not benefit from endocrine or HER2-targeted therapy [5–7].…”

Neoadjuvant Model as a Platform for Research in Breast Cancer and Novel Targets under Development in this Field

“…About 15-20% of all BC are considered HER2+ because of the overexpression of this receptor, and about 50% of these will also have HR expression [64]. The HER2+ subtype has an aggressive behavior that makes NAT an appealing therapeutic strategy to consider, especially in tumors > 2 cm and/or axillary positive lymph nodes.…”