Systemic Therapy De-Escalation in Early-Stage Triple-Negative Breast Cancer: Dawn of a New Era?

Cancers

Kazuaki Takabe¹  Ravi Kumar Gupta²  Mateusz Opyrchal³  Arya Mariam Roy⁴  Ashish Gupta⁴  Pawel Kalinski⁴  Shipra Gandhi⁴  Ajay Dhakal⁵ 

[1] Department of Immunology and Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;Department of Internal Medicine, Larkin Community Hospital, South Miami, FL 33143, USA;Department of Medicine, Indiana University Simons Comprehensive Cancer Center, Indianapolis, IN 46202, USA;Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;Department of Medicine, University of Rochester Medical Center, Rochester, NY 14648, USA;

关键词: triple-negative breast cancer;    de-escalation;    targeted therapy;    BRCA mutations;    chemotherapy;    neo adjuvant treatment;   

DOI  :  10.3390/cancers14081856

来源: DOAJ

【 摘 要 】

Early-stage triple negative breast cancer (TNBC) has been traditionally treated with surgery, radiation, and chemotherapy. The current standard of care systemic treatment of early-stage II and III TNBC involves the use of anthracycline-cyclophosphamide and carboplatin-paclitaxel with pembrolizumab in the neoadjuvant setting followed by adjuvant pembrolizumab per KEYNOTE-522. It is increasingly clear that not all patients with early-stage TNBC need this intensive treatment, thus paving the way for exploring opportunities for regimen de-escalation in selected subgroups. For T1a tumors (≤5 mm), chemotherapy is not used, and for tumors 6–10 mm (T1b) in size with negative lymph nodes, retrospective studies have failed to show a significant benefit with chemotherapy. In low-risk patients, anthracycline-free chemotherapy may be as effective as conventional therapy, as shown in some studies where replacing anthracyclines with carboplatin has shown non-inferior results for pathological complete response (pCR), which may form the backbone of future combination therapies. Recent advances in our understanding of TNBC heterogeneity, mutations, and surrogate markers of response such as pCR have enabled the development of multiple treatment options in the (neo)adjuvant setting in order to de-escalate treatment. These de-escalation studies based on tumor mutational status, such as using Poly ADP-ribose polymerase inhibitors (PARPi) in patients with BRCA mutations, and new immunotherapies such as PD1 blockade, have shown a promising impact on pCR. In addition, the investigational use of (bio)markers, such as high levels of tumor-infiltrating lymphocytes (TILs), low levels of tumor-associated macrophages (TAMs), and complete remission on imaging, also look promising. In this review, we cover the current standard of care systemic treatment of early TNBC and review the opportunities for treatment de-escalation based on clinical risk factors, biomarkers, mutational status, and molecular subtype.

【 授权许可】

Unknown