Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, 565-0871, Osaka, Japan.
Breast Cancer Res Treat. 2019 Feb;173(3):533-543. doi: 10.1007/s10549-018-5020-7. Epub 2018 Oct 25.
There is an urgent need for the development of a predictor of response to chemotherapy for ER-positive breast cancer which is less chemosensitive than for ER-negative breast cancer in order to avoid unnecessary chemotherapy. In the present study, intrinsic subtyping by PAM50 was evaluated for its ability to predict a response to chemotherapy.
For this study, 124 patients with ER-positive breast cancer treated with neoadjuvant sequential paclitaxel and FEC (NAC) were evaluated. Tumor biopsy specimens obtained before NAC were subjected to intrinsic subtyping (IS) by gene expression (GE) using PAM50 (PAM50-IS) or immunohistochemistry (IHC-IS).
Of the PAM50-ISs (Luminal A, Luminal B, HER2-enriched, and Basal-like), GE-Luminal A showed the lowest pCR rate (1.9%), and multivariate analysis revealed that GE-Luminal A was a significant (P = 0.031) predictor of non-pCR independently of other clinicopathological parameters, including Ki67, and tumor-infiltrating lymphocytes. Of the IHC-ISs, on the other hand, IHC-Luminal A was not significantly associated with pCR. We also found that breast tumors with low ER levels (1-9%), like ER-negative tumors, were mostly GE-HER2-enriched and GE-Basal-like, and more sensitive to NAC than those with high ER levels (≥ 10%).
GE-Luminal A intrinsically subtyped by PAM50 was the least sensitive to NAC and very unlikely to attain pCR. IHC-Luminal A identified by IHC, on the other hand, was not significantly predictive of pCR. In addition, PAM50 revealed that tumors with low ER (1-9%) were more like ER-negative tumors than ER-positive tumors, and most such cases should therefore would better be treated with chemotherapy.
为了避免不必要的化疗，迫切需要开发一种预测 ER 阳性乳腺癌化疗反应的方法，这种方法比 ER 阴性乳腺癌的化疗反应要差。在本研究中，评估了 PAM50 的内在亚型分类，以预测对化疗的反应。
本研究评估了 124 例接受新辅助序贯紫杉醇和 FEC（NAC）治疗的 ER 阳性乳腺癌患者。在 NAC 之前，采集肿瘤活检标本，通过基因表达（GE）使用 PAM50（PAM50-IS）或免疫组织化学（IHC-IS）进行内在亚型分类（IS）。
在 PAM50-IS（Luminal A、Luminal B、HER2 富集和基底样）中，GE-Luminal A 的 pCR 率最低（1.9%），多变量分析显示，GE-Luminal A 是独立于其他临床病理参数（包括 Ki67 和肿瘤浸润淋巴细胞）的非 pCR 的显著预测因子（P = 0.031）。另一方面，在 IHC-IS 中，IHC-Luminal A 与 pCR 无显著相关性。我们还发现，ER 水平低（1-9%）的乳腺肿瘤，如 ER 阴性肿瘤，主要是 GE-HER2 富集和 GE 基底样，对 NAC 更敏感。
PAM50 基因分型的 GE-Luminal A 对 NAC 最不敏感，极不可能达到 pCR。另一方面，通过 IHC 鉴定的 IHC-Luminal A 对 pCR 无显著预测作用。此外，PAM50 表明 ER（1-9%）低的肿瘤比 ER 阳性肿瘤更像 ER 阴性肿瘤，因此大多数此类病例最好用化疗治疗。
