Division of Breast Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ann Surg Oncol. 2024 Nov;31(12):8093-8101. doi: 10.1245/s10434-024-15889-3. Epub 2024 Aug 8.
Rates of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer have improved, especially among human epidermal growth factor 2-positive (HER2+) and triple-negative subtypes. The frequency and significance of biomarker profile change in residual disease are unclear. This study aimed to determine the rate of biomarker profile changes after NAC and the impact on clinical outcomes in a contemporary cohort.
Upon institutional review board approval, the study identified 634 consecutive patients treated with NAC between 2010 and 2022 at two academic institutions. The study cohort was focused on patients with residual disease who underwent biomarker profile retesting. Biomarker profile change for each subtype was compared across groups using Fisher-Irwin tests. Cox Proportional Hazards Model and Kaplan-Meier plots were performed to evaluate the association of changed versus unchanged biomarker profile with event-free survival.
Biomarker retesting was performed for 259 (61.4 %) of 422 patients with residual disease. Biomarker profile change occurred in 18.1 % overall and was significantly higher among those with pre-NAC HER2+ disease (32.7 %, 17/52) than among those with HER2-disease (14.5 %, 30/207) (p = 0.004). Conversion of pre-NAC biomarker profiles of HR+HER2- and HR+HER2+ to triple-negative breast cancer (TNBC) post-NAC may be associated with worse event-free survival, hazard ratios of 2.23 (95 % confidence interval [CI], 0.90-5.53; p = 0.08), trending toward significance, and 36.7 (95 % CI, 2.2-610.8; p = 0.01), respectively.
The results from one of the largest contemporary cohorts demonstrated that biomarker profile change in patients with residual disease after NAC was common. Furthermore, specific biomarker profile change in residual disease may have prognostic value. These findings strengthen the rationale for routine re-testing of biomarkers in residual disease after NAC.
新辅助化疗 (NAC) 后乳腺癌的病理完全缓解 (pCR) 率有所提高，尤其是在人表皮生长因子 2 阳性 (HER2+) 和三阴性亚型中。残留疾病中生物标志物谱变化的频率和意义尚不清楚。本研究旨在确定当代队列中 NAC 后生物标志物谱变化的频率及其对临床结果的影响。
经机构审查委员会批准，本研究在两个学术机构回顾性分析了 2010 年至 2022 年间接受 NAC 治疗的 634 例连续患者。该研究队列集中在接受残留疾病生物标志物谱再检测的患者。使用 Fisher-Irwin 检验比较各组间各亚型的生物标志物谱变化。采用 Cox 比例风险模型和 Kaplan-Meier 图评估改变与未改变的生物标志物谱与无事件生存的相关性。
对 422 例有残留疾病的患者中的 259 例进行了生物标志物检测。总体上，生物标志物谱发生变化的比例为 18.1%，且在 NAC 前 HER2+疾病患者中（32.7%，17/52）显著高于 HER2-疾病患者（14.5%，30/207）（p=0.004）。NAC 后将 NAC 前 HR+HER2-和 HR+HER2+的生物标志物谱转化为三阴性乳腺癌（TNBC）可能与无事件生存较差相关，风险比为 2.23（95%置信区间[CI]，0.90-5.53；p=0.08），有显著趋势，和 36.7（95%CI，2.2-610.8；p=0.01）。
本研究是目前最大的当代队列之一，结果表明 NAC 后残留疾病患者的生物标志物谱变化较为常见。此外，残留疾病中特定的生物标志物谱变化可能具有预后价值。这些发现为 NAC 后残留疾病中常规重新检测生物标志物提供了依据。
