Novel Agents for Metastatic Triple-Negative Breast Cancer: Finding the Positive in the Negative

Abstract

Metastatic triple-negative breast cancer (TNBC) is associated with a poor prognosis, and the development of better therapeutics represents a major unmet clinical need. Although the mainstay of treatment of metastatic TNBC is chemotherapy, advances in genomics and molecular profiling have helped better define subtypes of TNBC with distinct biologic drivers to guide the therapeutic development of targeted therapies, including AKT inhibitors for PI3K/AKT-altered TNBC, checkpoint inhibitors for PD-L1–positive TNBC, and PARP inhibitors for BRCA1/2 mutant TNBC. This progress may ultimately convert TNBC from a disease traditionally defined by the absence of therapeutically actionable receptors to one that is defined by the presence of discrete molecular targets with therapeutic implications. Furthermore, antibody drug conjugates have emerged as an important therapeutic strategy to target genomically complex tumors that lack actionable oncogenes but have overexpressed actionable surface receptors such as trop-2. In this article, we discuss promising novel agents for advanced TNBC, some of which have been incorporated into current clinical practice, and others that will likely change the therapeutic landscape and redefine the TNBC terminology in the near future.

Development and validation of nomograms for predicting survival in patients with de novo metastatic triple-negative breast cancer

“…Despite less direct evidences about the prognostic value of radiotherapy on mTNBC patients, it should be considered for selected patients based on the pattern and metachronicity of the disease. In line with previous studies, our results suggested that chemotherapy promoted survival independently 36 , 37 . Chemotherapy has been the main treatment for TNBC, the change of chemotherapy regimens not only improve the prognosis, but also provide more treatment options.…”

A Nomogram to Predict Disease-Free Survival Following Neoadjuvant Chemotherapy for Triple Negative Breast Cancer

“…Notably, for TNBC patients, who have fewer treatment options after NACT than the other phenotypes, these partial and complete responders represent a special group, with a favorable response to systemic therapy and the ability to overcome unfavorable tumor biology ( 15 ). However, the prognosis of TNBC is reported to be extremely poor once recurrence and metastasis have occurred ( 16 ). In our study, after a follow-up of a median of 41 months, 48 patients of the cohort experienced recurrence or metastasis, and bone or visceral metastasis were associated with extremely high mortality.…”

Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers

“…SG is a novel, third generation of antibody-drug conjugates (29). It is composed of a humanized anti-Trop-2 IgG antibody that is conjugated via a hydrolyzable linker to SN-38, which is an active metabolite of irinotecan (1,(30)(31)(32). Irinotecan is a camptothecin that inhibits the nuclear topoisomerase I enzyme, thereby inducing double-stranded DNA breaks during the S-phase of the cell cycle (33) (Figure 2).…”