Predictive and prognostic significance of BRCAness in HER2-negative breast cancer
Predictive and prognostic significance of BRCAness in HER2-negative breast cancer
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DOI：
10.1007/s12282-021-01319-9
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发表时间：
2022-01-05
期刊：
影响因子：
4
通讯作者：
Yamamoto, Yutaka
中科院分区：
文献类型：
--
作者：
Sueta, Aiko;Yamamoto-Ibusuki, Mutsuko;Yamamoto, Yutaka
研究背景BRCAness是一些散发性肿瘤和BRCA 1/2突变肿瘤共同的表型，导致同源重组缺陷。BRCAness在接受新辅助化疗（NAC）的HER 2阴性乳腺癌患者中的预测或预后价值尚未完全阐明。方法回顾性分析101例接受NAC治疗的I-III期高危HER 2阴性乳腺癌患者，采用多重连接依赖探针扩增法检测BRCA 1样表型。在BRCAness分析中，分析了101例患者中的95例。结果根据治疗前样本，70例（74%）患者为散发型肿瘤，25例（26%）患者为BRCA 1样肿瘤。在整个队列中，BRCA 1样表型与病理学完全缓解（pCR）率无关。在生存分析中，治疗前BRCA 1样表型与生存无关。另一方面，与散发特征相比，治疗后BRCA 1样患者明显显示较短的无复发生存期（对数秩P = 0.016）和乳腺癌特异性生存期（P < 0.001）。在多变量分析中，只有治疗后BRCA 1-表型是显著的预后因素（HR 5.67，95%CI 1.19-29.3）。此外，我们发现在19%的非pCR患者中，通过NAC发现BRCA 1样和散发型之间的表型变化。在治疗期间持续存在的散发性肿瘤或NAC后改变的散发性肿瘤中，治疗后Ki 67显著降低（分别为P < 0.0001，P = 0.0078）。结论BRCAness可作为判断标准化疗无效的HER 2阴性乳腺癌预后的生物学指标。我们的研究结果为确定需要替代疗法的患者铺平了道路。
Background BRCAness is characterized as the phenotypes shared between some sporadic tumors and BRCA1/2 mutation cancers resulting in defective homologous recombination. The predictive or prognostic value of BRCAness in HER2-negative breast cancer patients who have received neoadjuvant chemotherapy (NAC) is not fully elucidated. Methods We retrospectively selected 101 high-risk HER2-negative patients diagnosed with stage I-III breast cancer who underwent NAC treatment and evaluated BRCA1-like phenotype using multiplex ligation-dependent probe amplification assay. In an analysis of BRCAness, 95 out of 101 patients were analyzed. Results In total, 70 (74%) patients had sporadic-type tumors and 25 (26%) had BRCA1-like tumors according to pre-treatment samples. The BRCA1-like phenotype was not associated with pathological complete response (pCR) rate in the entire cohort. In survival analysis, pre-treatment BRCA1-like phenotype was not associated with survival. On the other hand, post-treatment BRCA1-like patients apparently showed shorter relapse-free survival (log-rank P = 0.016) and breast cancer-specific survival (P < 0.001) compared with sporadic features. In multivariate analysis, only the post-treatment BRCA1-phenotype was significant prognostic factors (HR 5.67, 95% CI 1.19-29.3). Furthermore, we found phenotype change between BRCA1-like and sporadic type through NAC in 19% of non-pCR patients. Post-treatment Ki67 significantly decreased in the persistent sporadic tumors during treatment or sporadic tumors changed after NAC (P < 0.0001, P = 0.0078, respectively). Conclusions BRCAness may be useful biomarkers to predict prognosis for HER2-negative breast cancer refractory to standard chemotherapy. Our results pave the way for identifying patients who require alternative therapies.