Early-stage Triple-negative Breast Cancer: Time to Optimize Personalized Strategies

Abstract

Triple-negative breast cancer (TNBC) accounts for approximately 15%-20% of breast cancers diagnosed worldwide, which amounts to almost 200 000 cases each year. Although historically TNBC is considered difficult to treat with a poor prognosis, there is emerging evidence showing excellent response rates in a subset of TNBC patients. Attempts to de-escalate chemotherapy in hormone-receptor-positive (HR+) and HER2-neu amplified breast cancer subtypes have been successful. At present, robust strategies to personalize therapy in early-stage TNBC do not exist, and despite excellent response rates in a subset of patients, all patients are exposed to the same several cycles of cytotoxic chemotherapy. Personalizing therapy in TNBC represents a challenge due to the scarcity of treatment options outside of cytotoxic chemotherapy and limited predictive and prognostic biomarkers to tailor treatment. Recent developments in understanding TNBC biology have sparked interest in exploring treatment optimization and personalization with the goal of achieving excellent response rates and long-term clinical outcomes, while simultaneously reducing physical, psychological, and financial toxicities for select patients. Here, we provide an update on the current evidence to support future studies examining de-escalating chemotherapy in patients with low-risk TNBC and adjuvant intensification strategies to improve outcomes for patients who are at high risk for systemic failure despite current standard-of-care treatments.

Genetic Heterogeneity, Tumor Microenvironment and Immunotherapy in Triple-Negative Breast Cancer

“…It was also demonstrated that TIL levels were lower in pre-chemotherapy when compared to post-chemotherapy samples and this supports the hypothesis that chemotherapy could induce an antitumor immune response [ 113 ]. It has also been observed that, when using neoadjuvant chemotherapy ( NACT ), increased TILs were associated with higher pCR , regardless of the type and duration of NACT therapy [ 114 ]. Patients with high- TIL residual disease experienced a significantly better metastases-free survival ( MFS ) when compared with patients in the low- TIL group [ 113 ].…”

“…TILs are reproducible biomarkers, and multiple studies have confirmed their prognostic value in TNBC ( Table 3 and Table 4 ) [ 114 ]. Immune response mediated by TILs is an important factor that has to be taken into consideration in treatment management; however, the presence or absence of particular subtypes and their ratio in cell population significantly influences the outcome.…”

Overcoming ROS Resistance of Photodynamic Therapy with Self‐Assembled Nano‐Prodrugs for Efficient Triple‐Negative Breast Cancer

“…[1][2][3] Most TNBC patients are often diagnosed at more advanced stages because it lack conspicuous early-stage symptoms and specific diagnostic biomarkers. [4][5] Unfortunately, traditional chemotherapy faces many obstacles in TNBC treatment, such as poor chemo-sensitivity and severe chemo-resistance, leading to high recurrence and distant metastasis. [6][7][8] Therefore, DOI: 10.1002/adfm.202309524 overcoming or bypassing the chemoresistance/sensitivity is crucial for enhanced TNBC treatment.…”

Triple-Negative Breast Cancer: A Review of Current Curative Intent Therapies

“…Historically, treatment options for TNBC were limited to cytotoxic chemotherapy. However, TNBC represents a highly heterogenous group of tumors, and understanding the molecular biology of a specific tumor allows for personalized treatment (in turn, minimizing unnecessary treatment toxicity while improving cancer outcomes) [ 4 ]. This article reviews the current landscape of curative-intent TNBC treatment strategies, in addition to looking ahead toward future directions and possible therapeutic approaches.…”