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曲妥珠单抗新辅助全身治疗基底型人表皮生长因子受体 2(HER2)阳性乳腺癌的有效性:来自日本乳腺癌研究集团(JBCRG)-C03 的回顾性队列研究结果。

Effectiveness of neo-adjuvant systemic therapy with trastuzumab for basal HER2 type breast cancer: results from retrospective cohort study of Japan Breast Cancer Research Group (JBCRG)-C03.

机构信息

Department of Breast Surgery, Kyoto University Graduate School of Medicine, 54 Kawaracho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Department of Breast Surgical Oncology, Social Medical Cooperation Hakuaikai, Kagoshima, Japan.

出版信息

Breast Cancer Res Treat. 2018 Oct;171(3):675-683. doi: 10.1007/s10549-018-4873-0. Epub 2018 Jul 3.

Abstract

PURPOSE

While human epidermal growth factor receptor 2 (HER2) target therapies have significantly improved the prognosis of patients with HER2-enriched breast cancer, differing clinical benefits and gene expression analyses suggest a divergent HER2 subgroup. We aimed to investigate whether the basal HER2 subtype of breast cancer has distinguished characteristics.

METHODS

We performed a substudy by using data from a retrospective multi-institutional cohort of JBCRG-C03. Between 2001 and 2011, we identified 184 eligible patients who received concurrent neo-adjuvant chemotherapy (NAC) with trastuzumab for hormone receptor-negative and HER2-positive breast cancer. We defined basal HER2 subtype breast cancer as HER2-positive, ER/PgR-negative, and basal markers (EGFR, CK14 or CK5/6) positive by immunohistochemistrical evaluation. The pathologic complete response (pCR) and disease-free survival (DFS) rates were compared between the two subtypes.

RESULTS

A total of 127 (69.0%) patients achieved pCR after NAC and 29 (15.8%) patients experienced events of DFS within a 42 month median follow-up period (interquartile range 26-58 months). Although the basal HER2 subtype was related with poor DFS (3 year DFS: non-basal HER2, 95.0%; basal HER2, 86.9%; adjusted HR 3.4; 95% CI 1.2-14.5), neither the subtype (pCR: non-basal HER2, 75%; basal HER2, 66.7%; adjusted OR 0.60; 95% CI 0.27-1.28) nor the degree of expression of basal markers was significantly related with the pCR rate.

CONCLUSION

Basal HER2 phenotype showed poor DFS, but equivalent pCR rate after concurrent neo-adjuvant chemotherapy with trastuzumab. A different treatment approach to basal-HER2 type is needed even for cases that achieved adequate clinical response after NAC.

摘要

目的

尽管人类表皮生长因子受体 2(HER2)靶向治疗显著改善了 HER2 富集型乳腺癌患者的预后,但不同的临床获益和基因表达分析表明存在不同的 HER2 亚组。我们旨在研究乳腺癌的基底型 HER2 亚型是否具有独特的特征。

方法

我们对 JBCRG-C03 的回顾性多机构队列数据进行了子研究。在 2001 年至 2011 年间,我们确定了 184 名符合条件的患者,这些患者接受了曲妥珠单抗联合新辅助化疗(NAC)治疗激素受体阴性和 HER2 阳性乳腺癌。我们通过免疫组织化学评估将基底型 HER2 亚型乳腺癌定义为 HER2 阳性、ER/PgR 阴性和基底标志物(EGFR、CK14 或 CK5/6)阳性。比较了两种亚型的病理完全缓解(pCR)率和无病生存(DFS)率。

结果

在 NAC 后,共有 127 名(69.0%)患者达到 pCR,在中位数为 42 个月(26-58 个月)的中位随访期间,有 29 名(15.8%)患者发生 DFS 事件。尽管基底型 HER2 亚型与较差的 DFS 相关(3 年 DFS:非基底型 HER2,95.0%;基底型 HER2,86.9%;调整 HR 3.4;95%CI 1.2-14.5),但亚型(pCR:非基底型 HER2,75%;基底型 HER2,66.7%;调整 OR 0.60;95%CI 0.27-1.28)和基底标志物的表达程度与 pCR 率均无显著相关性。

结论

基底型 HER2 表型显示出较差的 DFS,但在曲妥珠单抗联合新辅助化疗后具有相当的 pCR 率。即使在 NAC 后获得充分临床缓解的情况下,也需要对基底型-HER2 型采取不同的治疗方法。

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