Emerging Trends in the Treatment of Triple-Negative Breast Cancer in Canada: A Survey

Abstract

age at onset, large mean tumor size, high grade and higher incidence of node positivity at presentation compared to what is expected based on tumor size. TN status remains an independent risk factor for distant relapse and survival, with a rapid rise in distant relapse in the first three years after diagnosis 2,7 . additionally, patients with TN breast tumors have an increased propensity for lung and brain metastases, making these tumors especially challenging to treat.Molecular classification of breast cancer has further improved our understanding of the biology of this disease. Five intrinsic molecular subgroups of breast cancer have been described, including luminal a, luminal B, Her2-enriched, normal-like, and basal-like breast cancer (BLBC) 8 . Compared to the highly estrogen-sensitive luminal a subgroup, BLBC has significantly worse clinical outcomes with decreased recurrence free and overall survival 8 . BLBC and TNBC share many pathological, molecular, and clinical features, but they are not equivalent. Studies have demonstrated that not all TNBCs are basal-like 9,10 and not all BLBCs have a TN profile 10 . a study analyzing molecular markers differentiating TN tumor subtypes indicated that only 71% of TN tumors (n = 172) had a basal phenotype 9 . research has also suggested that non-basal TNBC may have a more favorable prognosis 8,10,11 .a "five marker" method has been proposed, combining the absence of er, Pr and Her2 with the expression of either epidermal growth factor receptor (eGFr) or cytokeratin (CK) 5/6, to differentiate BLBC from TNBC. While this method has demonstrated specificity for basal-like cancers, the definition has not been uniformly accepted. In the absence of a consensus regarding the optimal method of defining the basal-like subgroup of patients, TN status remains a clinical surrogate.Unlike patients with er/Pr-positive or Her2-overexpressing subtypes, systemic treatment options for patients with TNBC are limited to cytotoxic chemotherapy due to a lack of clinically-validated molecular treatment targets 12 . Standards have not ABSTRACTTriple-negative breast cancer (TNBC) has a poor prognosis compared to other subtypes and lacks common therapeutic targets, including Her2 and the estrogen and progesterone receptors. The clinicopathological heterogeneity of the disease and limited treatment options make clinical management particularly challenging. Here we present the results of a survey of Canadian clinical oncologists regarding treatment of TNBC, and review recent and ongoing clinical research in this area. Our survey results show that the majority of respondents use a combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while single agent capecitabine and platinum-based therapies are more common for subsequent lines of therapy. Despite the ongoing development of novel targeted therapies, chemotherapy remains the mainstay of treatment for TNBC.

Febrile Neutropenia Rates with Adjuvant Docetaxel and Cyclophosphamide Chemotherapy in Early Breast Cancer: Discrepancy between Published Reports and Community Practice—An Opdated Analysis

“…An updated U.S. Oncology trial report has demonstrated benefit in disease-free and overall survival for 4 cycles of docetaxel-cyclophosphamide (tc) chemotherapy over doxorubicin-cyclophosphamide chemotherapy and has also reported acceptable toxicity, with a fn rate of 5% 4 . The tc regimen has become very popular in Ontario, particularly in older age groups who are at increased risk of cardiotoxicity with anthracyclines and in patients eligible for trastuzumab 5 .…”

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

“…On the other hand, after the treatment, the monitoring of the disease should be evaluated by imaging techniques like MRI which is the most sensitive imaging method for measuring TNBC neoadjuvant response-treatment [105]. Precision medicine strategies identify strategic biomarkers in each oncological patient, providing a more effective and selective chemotherapy regimen [106]. Within the margins of personalized medicine, medical research suggests that for TNBC treatment, one of the most useful molecular targets is EGFR since it is positively expressed (around 60%) in TNBC [107].…”

Circulating Cell-Free Tumour DNA in the Management of Cancer

“…Mutations in the KRAS gene occur in multiple tumour types including colorectal carcinoma, non-small cell lung cancer and pancreatic carcinoma. Some mutations in the KRAS gene (approximately 40% of colorectal carcinomas) and the NRAS gene (approximately 1%–6%) are associated with poor prognosis and a lack of response to anti-EGFR antibody therapy such as cetuximab and panitumumab [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”