【原】HER2低表达乳腺癌术前化疗效果

　　大约50%的HER2阴性乳腺癌为HER2低表达，而非HER2零表达。德曲妥珠单抗等新型HER2抗体缀合药物对HER2低表达肿瘤的强大疗效，已经引起了大家的兴趣，考虑将HER2低表达作为乳腺癌的新亚型。不过，HER2低表达与零表达肿瘤相比，对化疗的敏感性和结局尚不明确。

　　2022年10月15日，欧洲癌症治疗研究组织《欧洲癌症杂志》在线发表法国马赛大学佩奥利卡尔梅特斯癌症中心的研究报告，对HER2低表达或零表达乳腺癌患者术前新辅助化疗后的病理完全缓解和无病生存率进行了比较。

　　该单中心回顾研究数据来自佩奥利卡尔梅特斯癌症中心数据库。HER2低表达定义为HER2免疫组织化学评分1+或2+且荧光原位杂交阴性，HER2零表达定义为免疫组织化学评分0。比较两组患者的临床病理特征、病理完全缓解（定义为ypT0或ypTis且pN0sn或ypN0）和无病生存率。

　　结果，2005年1月至2021年6月共计1111例接受新辅助化疗的患者数据可供分析。

　　HER2低表达率为41%，其中激素受体阳性占63%、激素受体阴性占37%（P<0.001）。

　　对于全部患者，HER2低表达与零表达相比，病理完全缓解率显著较低（23%比30%，P=0.013），但是该关联未见于多因素分析。对于激素受体阳性患者，HER2低表达与HER2零表达相比，病理完全缓解率显著较低（10%比16%，P=0.046）；但是对于激素受体阴性患者，HER2低表达与HER2零表达相比，病理完全缓解率相似（46%比42%，P=0.356），并且该结果可见于多因素分析。

　　无病生存率与HER2状态不存在相关性。

　　因此，该研究结果表明，HER2低表达与激素受体阳性存在相关性。HER2状态不影响激素受体阴性患者病理完全缓解率，而HER2低表达与激素受体阳性患者病理完全缓解率较低显著相关。

相关链接

• 乳腺癌HER2低表达病理检测进展
• HER2低表达乳腺癌诊治研究进展
• HER2低表达乳腺癌能否自立门户？
• HER2低表达乳腺癌临床和基因特征
• HER2低表达乳腺癌突破性疗法
• DESTINY-Breast04：HER2低表达晚期乳腺癌患者无进展生存和总生存双双改善！
• HER2阳性和HER2低表达乳腺癌临床研究进展
• HER2低表达乳腺癌及药物治疗进展
• HER2弱阳性乳腺癌大有文章
• HER2弱阳性晚期乳腺癌新靶向药疗效

Eur J Cancer. 2022 Oct 15;176:181-188. IF: 10.002

Pathological complete response rate and disease-free survival after neoadjuvant chemotherapy in patients with HER2-low and HER2-0 breast cancers.

de Nonneville A, Houvenaeghel G, Cohen M, Sabiani L, Bannier M, Viret F, Goncalves A, Bertucci F.

Aix-Marseille Univ, Institut Paoli-Calmettes, Marseille, France.

BACKGROUND: Half of HER2-negative breast cancers (BC) show HER2-low expression. The strong efficacy of recent anti-HER2 antibody-drug conjugates (ADC) in HER2-low tumours has risen the interest of HER2-low as a proper BC subtype. Chemosensitivity and prognosis of this subtype are not clear when compared to HER2-0 tumours. We investigated the pathological complete response (pCR) and disease-free survival (DFS) rates in BC patients receiving neoadjuvant chemotherapy for HER2-low or HER2-0 tumours.

METHODS: Data were collected from the Institut Paoli-Calmettes database. HER2-low tumours were defined by HER2 IHC score of 1+ or 2+ with negative FISH, and HER2-0 by IHC score of 0. Clinicopathological characteristics, pCR (defined as [ypT0/ypTis] and [pN0sn or ypN0]) and DFS rates were compared between the two cohorts.

RESULTS: From Jan/2005 to Jun/2021, 1111 patients receiving neoadjuvant chemotherapy were evaluable. The incidence of HER2-low was 41%, including 63% of hormone receptor (HR)-positive and 37% of HR-negative tumours (p < 0.001). In the whole population, the pCR rate was lower in HER2-low (23%) versus HER2-0 (30%) tumours (p = 0.013), but this association was lost in multivariate analysis. In HR-positive patients, HER2-low negatively impacted pCR rates when compared to HER2-0 (10% vs. 16%, p = 0.046), but not in HR-negatives (46% vs. 42%), and this result was maintained in multivariate analysis. No correlation existed between DFS and HER2-status.

CONCLUSION: HER2-low is associated with HR positivity. HER2 status did not impact pCR in HR-negative patients, whereas HER2-low was associated with lower pCR rate in HR-positive patients.

KEYWORDS: Breast cancer; HER2-low; Neoadjuvant chemotherapy; Pathologic response

PMID: 36257173

DOI: 10.1016/j.ejca.2022.09.017