Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment

Abstract

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat. To date, therapies directed to specifi c molecular targets have rarely achieved clinically meaningful improvements in outcomes of patients with TNBC, and chemotherapy remains the standard of care. Here, we seek to review the most recent efforts to classify TNBC based on the comprehensive profi ling of tumors for cellular composition and molecular features. Technologic advances allow for tumor characterization at ever-increasing depth, generating data that, if integrated with clinical-pathologic features, may help improve risk stratifi cation of patients, guide treatment decisions and surveillance, and help identify new targets for drug development.Signifi cance: TNBC is characterized by higher rates of relapse, greater metastatic potential, and shorter overall survival compared with other major breast cancer subtypes. The identifi cation of biomarkers that can help guide treatment decisions in TNBC remains a clinically unmet need. Understanding the mechanisms that drive resistance is key to the design of novel therapeutic strategies to help prevent the development of metastatic disease and, ultimately, to improve survival in this patient population. TNBC AND INTRINSIC BREAST CANCER SUBTYPESEarly transcriptomic profi ling of breast cancer using microarrays classifi ed tumors into fi ve intrinsic subtypes: luminal-A, luminal-B, HER2-enriched, basal-like, and a normal breast-like group ( 5,6 ). Although all intrinsic subtypes can be found within immunohistochemically defi ned triplenegative disease, basal-like tumors exhibit the greatest overlap with TNBC. Between 50% and 75% of TNBC have basal phenotype, and approximately 80% of basal-like tumors are ER-negative/HER2-negative ( Fig. 2 ; refs. 7, 8 ). Characterization Research.on August 1, 2020.

EN1 Is a Transcriptional Dependency in Triple-Negative Breast Cancer Associated with Brain Metastasis

“…Triple-negative breast cancer (TNBC) constitutes 10%-20% of breast cancer cases in the United States and more commonly affects younger and African-American women (2,3). TNBCs have higher risk of developing distant metastases and in general have poor clinical outcome.…”

Role of Immunotherapy in Triple-Negative Breast Cancer

“…Triple-negative breast cancer (TNBC), defined by the lack of estrogen and progesterone receptors and HER2, accounts for 15% to 20% of all breast cancers and typically displays aggressive behavior, including earlier recurrence and metastasis. 1 The predominant systemic therapy for most metastatic TNBC (mTNBC) is chemotherapy, but responses are often short-lived, and patients have a median overall survival (OS) of 12 to 18 months. 1 Therefore, improved therapies are urgently needed.…”

“…1 The predominant systemic therapy for most metastatic TNBC (mTNBC) is chemotherapy, but responses are often short-lived, and patients have a median overall survival (OS) of 12 to 18 months. 1 Therefore, improved therapies are urgently needed.…”

Serine-Arginine Protein Kinase 1 (SRPK1) as a Prognostic Factor and Potential Therapeutic Target in Cancer: Current Evidence and Future Perspectives

“…More studies that investigate the distinct molecular subtypes of each cancer type (e.g., breast cancer: hormone positive, HER2-enriched, and BLBCs) rather than regard each cancer as single entity, should be performed. In BLBCs, in contrast to hormone and HER2 positive breast cancers, targeted therapies are still ineffective and toxic chemotherapy is the only viable option [16,92]. Van Roosmalen et al directed their study to the highly aggressive BLBCs [33], setting an example for future research in this field.…”