Gupta Ravi Kumar, Roy Arya Mariam, Gupta Ashish, Takabe Kazuaki, Dhakal Ajay, Opyrchal Mateusz, Kalinski Pawel, Gandhi Shipra
Department of Internal Medicine, Larkin Community Hospital, South Miami, FL 33143, USA.
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Cancers (Basel). 2022 Apr 7;14(8):1856. doi: 10.3390/cancers14081856.
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.
早期三阴性乳腺癌（TNBC）传统上采用手术、放疗和化疗进行治疗。目前，早期II期和III期TNBC的标准全身治疗方案是在新辅助治疗中使用蒽环类药物-环磷酰胺和卡铂-紫杉醇联合帕博利珠单抗，随后根据KEYNOTE-522试验进行辅助帕博利珠单抗治疗。越来越明显的是，并非所有早期TNBC患者都需要这种强化治疗，从而为探索在特定亚组中降低治疗方案强度的机会铺平了道路。对于T1a期肿瘤（≤5mm），不使用化疗，对于大小为6-10mm（T1b）且淋巴结阴性的肿瘤，回顾性研究未能显示化疗有显著益处。在低风险患者中，不含蒽环类药物的化疗可能与传统治疗一样有效，如一些研究表明，用卡铂替代蒽环类药物在病理完全缓解（pCR）方面显示出非劣效结果，这可能构成未来联合治疗的基础。我们对TNBC异质性、突变以及pCR等反应替代标志物的最新认识进展，使得在（新）辅助治疗中能够开发多种治疗选择以降低治疗强度。这些基于肿瘤突变状态的降阶梯研究，如在携带BRCA突变的患者中使用聚ADP核糖聚合酶抑制剂（PARPi），以及新的免疫疗法如PD1阻断，已显示出对pCR有良好影响。此外，（生物）标志物的研究性应用，如高水平的肿瘤浸润淋巴细胞（TILs）、低水平的肿瘤相关巨噬细胞（TAMs）以及影像学上的完全缓解，也前景乐观。在本综述中，我们涵盖了早期TNBC的当前标准全身治疗方案，并基于临床风险因素、生物标志物、突变状态和分子亚型回顾了治疗降阶梯的机会。
