Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up

Abstract

Studies on well characterized, large populations of estrogen receptor (ER)/progesterone receptor (PgR)/HER2-negative [triple-negative (TN)] breast cancer (BC) patients with long-term follow-up are lacking. In this study, we analyze clinical outcomes of TN BC and implications of epidermal growth factor receptor (EGFR) expression. Clinical and biologic features, time to first recurrence (TTFR), and overall survival (OS) were compared in 253 TN versus 1,036 ER positive, PgR positive, HER2-negative [estrogen-driven (ED)] BC. Compared to ED, TN tumors were larger (p = 0.02), more proliferative (high S-phase 54 vs. 17 %, p < 0.0001), more aneuploid (64 vs. 43 %, p < 0.0001) and more likely EGFR positive (≥10 fmol/mg by radioligand-binding assay, 49 vs. 7 %, p < 0.0001). Among TN, EGFR-positive BC were larger (p = 0.0018), more proliferative (p < 0.0001), and more aneuploid, (p < 0.0001) than EGFR-negative BC. Adjuvant-treated TN patients had shorter TTFR (p = 0.0003), and OS (p = 0.0017), than ED patients. However, in untreated patients, no differences in TTFR and OS were observed at 8 years median follow-up. Among TN patients, EGFR expression was not associated with worse outcome. TN tumors have a worse outcome in systemically treated patients but not in untreated patients. EGFR expression, does not predict for worse long-term survival.

Triple Negative Breast Cancer: A Review of Clinicopathologic Characteristics And Treatment Options

“…About 75-80% of the breast cancers are hormone receptor positive. In general, when compared to hormone receptor positive tumors, TNBC have a higher proliferation rate (54% vs 17%) [11,12]. Over the past decade, gene expression profiling and their correlation to immunohistochemical markers have led to the identification of different molecular subtypes of breast cancer: luminal A, luminal B, HER2 positive, and basal-like [4,13,14].…”

“…Compared to hormone receptor positive tumors, patients with TNBC are 6.5 times more likely to express EGFR (7% vs 49%, respectively) [11]. However, a recent analysis of 253 TNBC found no correlation between EGFR expression and unfavorable longterm outcomes [11].…”

“…Compared to hormone receptor positive tumors, patients with TNBC are 6.5 times more likely to express EGFR (7% vs 49%, respectively) [11]. However, a recent analysis of 253 TNBC found no correlation between EGFR expression and unfavorable longterm outcomes [11]. In a retrospective study, TNBC overexpressing EGFR had better pCR rates when compared to non-TNBC in the neoadjuvant setting; however, on multivariate analysis, EGFR expression was not an independent predictor of OS (p= 0.7) [80].…”

Novel therapeutic strategies for patients with triple-negative breast cancer

“…“Triple-negative” BC (TNBC) was mentioned for the first time in 2005, and, since then, this term has been appearing in publications 2. TNBC, identified as a clinically important subgroup of BC in the early 2000s and characterized by an especially poor prognosis,3 is an aggressive BC subtype lacking the expression of estrogen receptor (ER) and progesterone receptor and overexpression or gene amplification of human epidermal growth factor receptor 2 (HER2). TNBC accounts for a disproportionate number of deaths from BC, especially among premenopausal African-American and Hispanic women who have younger age, more advanced stage distribution, and higher incidence rates 4–6…”

The receptor tyrosine kinase Met and the protein tyrosinephosphatase PTPN2 in breast cancer

“…This subtype remains the most fatal of the breast cancers, mainly because of the aggressiveness of the tumour and the unavailability of targeted therapy [41][42][43].…”