Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients

Abstract

Despite treatment with standard dose anthracycline-based chemotherapy, the clinical outcome of TN and BL cancers remains poor. Alternative chemotherapeutic regimens and/or novel therapeutic approaches are warranted. Although a significant phenotypic overlap exists between TN and basal-like tumours, the TN phenotype is not an ideal surrogate marker for basal-like breast cancers.

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

“…This subgroup may be amenable to specific therapeutic strategies such as inhibitors of the PARP enzyme. 32,[81][82][83]130,131 Consistent with this hypothesis, results of PARP inhibitor phase I and phase II clinical trials that have included patients with BRCA-deficient tumors have been encouraging [132][133][134] and sustained responses in patients with BRCA1/2-deficient breast or ovarian metastatic cancers have been observed. Furthermore, preliminary results of a phase II clinical trial revealed that addition of BSI-201, a PARP inhibitor, to gemcitabine/carboplatin chemotherapy led to a significantly increased clinical benefit and longer progression-free survival.…”

“…1,15,69 Taken together, these results are in accord with the concept that the triple-negative phenotype is not an ideal surrogate marker for basal-like breast cancers. 60,70,81 Relationship between basal-like breast cancer and BRCA1 germ-line mutations There is increasing evidence to suggest a link between BRCA1 pathway and basal-like breast cancers. 82,83 The majority of tumors arising in BRCA1 germ-line mutation carriers, in particular those diagnosed before 50 years of age, have morphological features similar to those described in basal-like cancers 84,85 and show a basal-like phenotype as defined by immunohistochemistry 86,87 or expression arrays.…”

“…129 Finally, as mentioned earlier, a group of basal-like and triple-negative breast carcinomas have been shown to have a dysfunctional BRCA1 pathway. 32,65,[81][82][83] A significant number of these cases lack competent homologous recombination DNA repair. This subgroup may be amenable to specific therapeutic strategies such as inhibitors of the PARP enzyme.…”

High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

“…8 EGFR is a well-established treatment target for colorectal cancer, non-small cell lung cancer, and squamous cell carcinoma of the head and neck. In breast cancer, EGFR overexpression has been reported in up to 78% of triple-negative breast cancers, [9][10][11][12][13][14][15][16][17][18][19][20] more than in non-triple-negative breast cancers, 12,15 suggesting that EGFR is a potential therapeutic target for triple-negative breast cancer. EGFR tyrosine kinase inhibitors have yielded insignificant response rates in breast cancer, [21][22][23] possibly due to the lack of patient selection in these studies; they were not restricted to breast cancers with EGFR overexpression or triple-negative breast cancers.…”

Letter to the Editor

“…Other markers, such as p53 overexpression, have been considered a common marker of basal-like breast carcinoma, 6 but it has also been detected in 11.3% of ER-positive breast carcinomas. 7 Therefore, current evidence is still insufficient to support the routine analysis of p53 in clinical practice.…”