Abstract

Triple-negative breast cancers (TNBCs) are aggressive tumors that are more common in young women, African American populations, and those with hereditary mutations. These tumors are notable for their high recurrence rate and predilection for chemoresistance. The goal of this narrative review is to describe the current treatment options for patients diagnosed with TNBC and to review the studies that have put forward these recommendations. We searched PubMed and Cochrane databases for free full-text, English-language studies published within the last several years pertaining to the search items “triple negative breast cancer” and “treatment”. We included clinical trials and retrospective reviews that had clear designs and assessed their findings against a gold standard or placebo and included evidence of overall response and/or survival outcomes. Patients with early-stage (I-III) TNBC still benefit from treatment with chemotherapeutic regimens involving anthracyclines, taxanes, and antimetabolites. Platinum-based therapies have been shown to improve the overall pathologic complete response (pCR), but there is conflicting evidence with regard to their contribution to disease-free survival (DFS) and overall survival (OS), even with the addition of a poly (ADP-ribose) polymerase (PARP) inhibitor. Patients with residual disease after neoadjuvant chemotherapy and surgical intervention have shown a significant improvement in OS when treated with adjuvant capecitabine. The high mutation burden in metastatic TNBC (mTNBC) allows for targeted therapies and immune checkpoint inhibitors. mTNBCs that express programmed death ligand-1 (PD-L1) receptors may achieve improved response and survival if their regimen includes a monoclonal antibody. Antibody-drug conjugates (ADCs) can deliver high doses of chemotherapy and significantly impact survival in mTNBC regardless of the level of biomarkers expressed by the tumor cells. PARP inhibitors significantly improve survival in newly diagnosed, treatment-naive mTNBC, but have shown mixed results in patients with a history of previous therapy. PARP inhibitors may also target patients with somatic breast cancer (BRCA) and partner and localizer of BRCA-2 (PALB2) mutations, which would allow for more options in this subset of patients. While other rare targets have shown mixed results, the future of treatment may lie in anti-androgen therapy or the development of cancer vaccinations that may increase the immunogenicity of the tumor environment.The management of TNBC includes treatment with multimodal chemotherapy, immune checkpoint inhibitors, and ADCs. The optimal approach depends on a multitude of factors, which include the stage of the tumor, its unique mutational burden, comorbid conditions, and the functional status of the patient. Physicians should be familiar with the advantages and disadvantages of each therapy in order to appropriately counsel and guide their patients.

Highlights

  • BackgroundAdvancements in genomic techniques have improved the assessment and diagnosis of breast cancer, enabling the classification of the condition into four molecular subtypes based on the predominant genes [1,2]

  • The landmark KEYNOTE trial [19] found that patients with early Triple-negative breast cancers (TNBCs) had a significantly higher pathologic complete response (pCR) when treated with pembrolizumab plus neoadjuvant chemotherapy as opposed to neoadjuvant chemotherapy with placebo (64.8% vs. 51.2%, respectively; p

  • Patients with early triple-negative breast cancer retain the benefit from standard anthracycline/taxane regimens

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Summary

Introduction

Advancements in genomic techniques have improved the assessment and diagnosis of breast cancer, enabling the classification of the condition into four molecular subtypes based on the predominant genes [1,2]. Triple-negative breast cancers (TNBCs) are a heterogenous subgroup characterized by their lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). TNBC is unique in that its lack of receptor expression often portends a poorer prognosis and poses unique therapeutic challenges. Breast cancer remains the most common cancer diagnosed in women, with an overall lifetime risk of 13% [5]. In 2021, 282,000 new cases of breast cancer were diagnosed, with approximately 13.1 new cases of TNBC per 100,000 women [5]. TNBC carries a higher mortality risk with a relative five-year survival of 65% in

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