Department of Breast and Endocrine Surgery, Osaka Breast Clinic, Osaka City, Japan,
Department of Breast and Endocrine Surgery, Osaka Breast Clinic, Osaka City, Japan.
Oncology. 2020;98(1):35-41. doi: 10.1159/000502910. Epub 2019 Oct 1.
It is unclear for whom new anti-human epidermal growth factor receptor 2 (anti-HER2) agents, such as pertuzumab and T-DM1, should be considered. We investigated prognostic factors before neoadjuvant chemotherapy (NAC) among HER2-positive invasive breast cancer patients and those after NAC among patients who did not achieve pathological complete response (pCR) using conventional adjuvant trastuzumab.
HER2-positive primary breast cancer patients treated using NAC containing trastuzumab were enrolled between September 2006 and June 2017 at the Osaka Breast Clinic. Patients with distant metastasis or using NAC containing pertuzumab were excluded. The main outcome was disease-free survival (DFS). We investigated pre- and post-NAC prognostic factors using the log-rank test and Cox proportional hazards model.
In total, 157 patients were included. Among the pre-NAC prognostic factors, younger age (under 40 years old) and positive clinical nodal status were significantly poorer prognostic factors (hazard ratio [HR] 3.47, 95% CI 1.06-10.12, p = 0.041 and HR 3.32, 95% CI 1.03-14.78, p = 0.045) by multivariate analysis. Among the post-NAC prognostic factors, patients with non-pCR (3-year DFS; 85 vs. 96%, p = 0.022) had a poorer DFS than patients with pCR. DFS was assessed for non-pCR patients (n = 64). High post-NAC Ki-67 status (≥20%; HR 6.73, 95% CI 1.82-31.93, p = 0.004) was a significant and large post-NAC tumor size (≥2 cm; HR 3.65, 95% CI 0.97-14.71, p = 0.056) was a marginally significant prognostic factor by multivariate analysis. After having combined them, high post-NAC Ki-67 status or large post-NAC tumor size was also a significant prognostic factor (HR 5.75, 95% CI 1.32-16.12, p = 0.017).
Positive clinical nodal status and young age were found to be prognostic factors before NAC in HER2-postive invasive breast cancer patients. A high post-NAC Ki-67 status and large post-NAC tumor size were significant and marginally significant prognostic factors, respectively, after NAC in patients who did not achieve pCR. New anti-HER2 agents, such as pertuzumab and T-DM1, should be considered for the patients with those prognostic factors.
尚不清楚新的抗人表皮生长因子受体 2（抗 HER2）药物，如 pertuzumab 和 T-DM1，应考虑用于哪些患者。我们研究了 HER2 阳性浸润性乳腺癌患者接受新辅助化疗（NAC）前和未达到病理完全缓解（pCR）的患者接受 NAC 后的预后因素，这些患者使用了常规辅助曲妥珠单抗。
2006 年 9 月至 2017 年 6 月期间，在大阪乳腺诊所招募了使用含曲妥珠单抗的 NAC 治疗的 HER2 阳性原发性乳腺癌患者。排除远处转移或使用含 pertuzumab 的 NAC 的患者。主要结局是无病生存（DFS）。我们使用对数秩检验和 Cox 比例风险模型研究了 NAC 前后的预后因素。
共纳入 157 例患者。在 NAC 前的预后因素中，年龄较小（<40 岁）和阳性临床淋巴结状态是显著的预后不良因素（多变量分析的 HR 分别为 3.47，95%CI 1.06-10.12，p=0.041 和 HR 3.32，95%CI 1.03-14.78，p=0.045）。在 NAC 后的预后因素中，非 pCR（3 年 DFS；85% vs. 96%，p=0.022）患者的 DFS 明显差于 pCR 患者。对非 pCR 患者（n=64）进行了 DFS 评估。高 NAC 后 Ki-67 状态（≥20%；HR 6.73，95%CI 1.82-31.93，p=0.004）是显著的，NAC 后肿瘤较大（≥2cm；HR 3.65，95%CI 0.97-14.71，p=0.056）是一个边缘显著的预后因素。经多变量分析后，高 NAC 后 Ki-67 状态或大 NAC 后肿瘤大小也是显著的预后因素（HR 5.75，95%CI 1.32-16.12，p=0.017）。
在 HER2 阳性浸润性乳腺癌患者中，NAC 前的阳性临床淋巴结状态和年轻年龄被发现是预后因素。在未达到 pCR 的患者中，NAC 后高 NAC 后 Ki-67 状态和大 NAC 后肿瘤大小分别是显著和边缘显著的预后因素。对于具有这些预后因素的患者，应考虑使用新的抗 HER2 药物，如 pertuzumab 和 T-DM1。
