Ivanovic Nebojsa, Bjelica Dragana, Loboda Barbara, Bogdanovski Masan, Colakovic Natasa, Petricevic Simona, Gojgic Milan, Zecic Ognjen, Zecic Katarina, Zdravkovic Darko
Department of Surgical Oncology, University Hospital Medical Center (UHMC) "Bezanijska kosa", Belgrade, Serbia.
Department of Surgery, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Front Oncol. 2023 Jul 18;13:1207948. doi: 10.3389/fonc.2023.1207948. eCollection 2023.
Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) of early breast cancer (EBC) has been recognized as a good prognostic factor in the treatment of breast cancer because of its significant correlation with long-term disease outcome. Based on this correlation, pCR has been accepted by health authorities (FDA, EMA) as a surrogate endpoint in clinical trials for accelerated drug approval. Moreover, in recent years, we have observed a tendency to treat pCR in routine clinical practice as a primary therapeutic target rather than just one of the pieces of information obtained from clinical trials. These trends in routine clinical practice are the result of recommendations in treatment guidelines, such as the ESMO recommendation "…to deliver all planned (neoadjuvant) treatment without unnecessary breaks, i.e. without dividing it into preoperative and postoperative periods, irrespective of the magnitude of tumor response", because "…this will increase the probability of achieving pCR, which is a proven factor for a good prognosis…". We hypothesize that the above recommendations and trends in routine clinical practice are the consequences of misunderstanding regarding the concept of pCR, which has led to a shift in its importance from a prognostic factor to a desired treatment outcome. The origin of this misunderstanding could be a strong subconscious incentive to achieve pCR, as patients who achieved pCR after NAST had a better long-term outcome compared with those who did not. In this paper, we attempt to prove our hypothesis. We performed a comprehensive analysis of the therapeutic effects of NAST and adjuvant systemic therapy (AST) in EBC to determine whether pCR, as a phenomenon that can only be achieved at NAST, improves prognosis per se. We used published papers as a source of data, which had a decisive influence on the formation of the modern attitude towards EBC therapy. We were unable to find any evidence supporting the use of pCR as a desired therapeutic goal because NAST (reinforced by pCR) was never demonstrated to be superior to AST in any context.
早期乳腺癌（EBC）新辅助全身治疗（NAST）后的病理完全缓解（pCR），因其与长期疾病转归显著相关，已被视为乳腺癌治疗中的一个良好预后因素。基于这种相关性，pCR已被卫生当局（美国食品药品监督管理局、欧洲药品管理局）接受为临床试验中加速药物批准的替代终点。此外，近年来，我们观察到在常规临床实践中，有一种将pCR作为主要治疗目标而非仅仅是从临床试验中获得的信息之一的趋势。常规临床实践中的这些趋势是治疗指南中建议的结果，例如欧洲肿瘤内科学会（ESMO）的建议“……进行所有计划的（新辅助）治疗，不要有不必要的中断，即不要将其分为术前和术后阶段，无论肿瘤反应程度如何”，因为“……这将增加实现pCR的概率，而pCR是良好预后的一个已证实因素……”。我们假设，上述常规临床实践中的建议和趋势是对pCR概念误解的结果，这导致了其重要性从一个预后因素转变为一个期望的治疗结果。这种误解的根源可能是实现pCR的强烈潜意识动机，因为与未达到pCR的患者相比，NAST后达到pCR的患者长期转归更好。在本文中，我们试图证明我们的假设。我们对EBC中NAST和辅助全身治疗（AST）的治疗效果进行了全面分析，以确定pCR作为一种仅能在NAST时实现的现象，本身是否能改善预后。我们使用已发表的论文作为数据来源，这些论文对现代EBC治疗态度的形成具有决定性影响。我们未能找到任何支持将pCR作为期望治疗目标的证据，因为在任何情况下，NAST（由pCR强化）从未被证明优于AST。
