Neoadjuvant chemotherapy for “Triple Negative” breast cancer: a review of current practice and future outlook

Abstract

Patients with breast cancer who achieve a complete pathologic response (pCR) after preoperative (neoadjuvant) chemotherapy have an improved prognosis compared to those with residual disease; pCR being a good surrogate of long-term survival and cure from breast cancer. Despite their relative chemosensitivity, less than 25% of all patients with HER2/neu negative (0-2+), and hormone receptors (HR) negative tumors, so-called "Triple Negative" breast cancer (TNBC) treated with standard preoperative chemotherapy achieve pCR. Among patients with residual disease (no pCR) following neoadjuvant chemotherapy, patients with TNBC have the worst prognosis and overall survival. These patients lack the benefit of subsequent targeted therapy. Many studies have addressed improving the efficacy of neoadjuvant chemotherapy by including different cytotoxic agents, biologic modifiers, regimens, and schedules. Up to now, apart from trastuzumab for HRE2/neu+ tumors, none of the targeted agents can be considered a standard therapeutic option for primary systemic treatment. We hereby review the current literature on neoadjuvant chemotherapy for breast cancer, emphasizing treatment of TNBC. We also discuss potentially new therapeutic strategies that target this high risk group.

The Residual Tumor Autophagy Marker LC3B Serves as a Prognostic Marker in Local Advanced Breast Cancer after Neoadjuvant Chemotherapy

“…Furthermore, the prognostic value of LC3B was most significant in patients with TNBC. TNBC is the biologic entity that lacks ER, PR, and HER-2 expression; although TNBC is initially chemosensitive to NCT, patients with non-pCR with residual TNBC disease generally have an unfavorable prognosis with a short RFS and OS (30). Furthermore, several reports have suggested that TNBC represents a heterogeneous group comprising subtypes with different outcomes (31)(32)(33), as TNBC with The prognostic value of LC3B was most significant among patients with TNBC for both RFS and OS (P ¼ 0.007 and 0.006, respectively).…”

Downregulation of BCSG1 may correlate with better outcome of neoadjuvant chemotherapy for triple-negative breast cancer

“…TNBC is a subtype of breast cancer. Although TNBC is an initially chemosensitive disease, less than 25% of patients with TNBC who received standard NAC achieved pCR and the remaining patients usually have a poor prognosis (9). Several approaches have been reported to improve the NAC efficacy in previous studies, including different anthracycline-based regimens, anthracycline-taxane combinations, sequential regimens and dose-dense schedules (9).…”

“…Although TNBC is an initially chemosensitive disease, less than 25% of patients with TNBC who received standard NAC achieved pCR and the remaining patients usually have a poor prognosis (9). Several approaches have been reported to improve the NAC efficacy in previous studies, including different anthracycline-based regimens, anthracycline-taxane combinations, sequential regimens and dose-dense schedules (9). Furthermore, certain researchers have revealed other characteristics of TNBC, including overexpression of EGFR and c-KIT, increased proliferative rate through MAP kinase and Akt pathways (10) and providing some basis for the targeted therapy in those patients.…”

“…Inhibition of PARP may improve the efficacy of certain DNA-damaging chemicals, including platinum compounds and topoisomerase inhibitors (11,12). However, lack of consistency and the complexity of the analysis and interpretation of molecular classification data hindered the application of these targets in the treatment of TNBC (9). Since TNBC patients cannot benefit from target endocrine therapy and anti-HER-2 treatment, systemic chemotherapy treatment is the only one option in combination with local surgery and radiotherapy.…”

MicroRNA and Drug Delivery

“…Current chemotherapeutic regimens continue to rely on heavy dosing to overcome their low cancer specificity and poor penetration [13][14][15]. Immunotargeting strategies have aided tumor targeting, but they still fall short of being substantially efficacious across a wide range of tumor types and are often limited in their scope because of the specificity of their targets [16,17].…”