Clinical outcomes of early-stage triple-negative breast cancer after neoadjuvant chemotherapy according to HER2-low status☆

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-11-01 DOI:10.1016/j.esmoop.2024.103973

A.S. Raghavendra , D.B. Zakon , Q. Jin , A. Strahan , M. Grimm , M.E. Hughes , M. Cherian , J. Vincuilla , T. Parker , P. Tarantino , E.A. Mittendorf , T.A. King , V. Valero , D. Tripathy , S.M. Tolaney , N. Tayob , N.U. Lin , D.G. Stover , C.H. Barcenas , A.C. Garrido-Castro

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Abstract

Background

The impact of human epidermal growth factor receptor 2 (HER2) expression determined by immunohistochemistry (IHC) on outcomes in early-stage triple-negative breast cancer (eTNBC) is unclear. Using a large, multi-institutional cohort, we evaluated outcomes by HER2 IHC status in patients with eTNBC who received neoadjuvant therapy (NAT).

Patients and methods

Patients with stage I-III TNBC who received NAT and underwent surgery from January 2016 to June 2019 were identified from three databases. HER2 expression was defined as low (IHC1+ or 2+/FISH not amplified) or HER2 IHC score 0 by local testing at diagnosis. Pathological complete response (pCR) rates were compared using logistic regression adjusted for multiple factors. Survival outcomes were estimated using Kaplan–Meier and Cox proportional hazards models.

Results

Among 977 consecutive patients, 388 (39.7%) had HER2-low and 589 (60.3%) had HER2 IHC score 0 tumors. Median age at eTNBC diagnosis was 50.3 years (range 21.0-83.4 years). At baseline, clinical nodal positivity rate was significantly higher in HER2-low (55.0%) versus HER2 IHC score 0 tumors (46.6%) (P = 0.011); pCR rates were similar (32.0% versus 32.6%; adjusted P = 0.924). At a median follow-up of 3.5 years, recurrence-free survival (RFS) did not vary significantly between HER2-low versus HER2 IHC score 0 among patients with pCR (adjusted P = 0.368) or residual disease (RD) after NAT (adjusted P = 0.573). Distant RFS and overall survival (OS) did not differ by HER2 category for patients with pCR [distant RFS (DRFS), adjusted P = 0.509; OS, adjusted P = 0.514] or RD (DRFS, adjusted P = 0.812; OS, P = 0.285). Discordance of tumor HER2 status was seen in 31.1% of HER2 IHC score 0 cases, with HER2 expression observed post-treatment; 34.8% of HER2-low cases showed discordance, with absent HER2 expression in RD.

Conclusions

In this large cohort of patients with eTNBC treated with NAT, HER2-low status was not associated with pCR or survival after adjusting for clinical factors. The discordance in HER2 IHC pre- and post-NAT likely reflects challenges in HER2 quantification and heterogeneity.

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早期三阴性乳腺癌新辅助化疗后的临床疗效（根据HER2-低状态而定）☆☆

背景通过免疫组化（IHC）确定的人类表皮生长因子受体 2（HER2）表达对早期三阴性乳腺癌（eTNBC）预后的影响尚不明确。我们利用一个大型多机构队列，评估了接受新辅助治疗（NAT）的eTNBC患者的HER2 IHC状态对预后的影响。患者和方法从三个数据库中确定了2016年1月至2019年6月期间接受NAT并接受手术的I-III期TNBC患者。HER2表达被定义为低表达（IHC1+或2+/FISH未扩增）或诊断时经当地检测HER2 IHC评分为0。病理完全缓解率（pCR）采用逻辑回归法进行比较，并对多种因素进行调整。结果在 977 例连续患者中，388 例（39.7%）为 HER2 低分化肿瘤，589 例（60.3%）为 HER2 IHC 0 分化肿瘤。确诊 eTNBC 时的中位年龄为 50.3 岁（21.0-83.4 岁）。基线时，HER2 低（55.0%）肿瘤的临床结节阳性率明显高于 HER2 IHC 评分为 0 的肿瘤（46.6%）（P = 0.011）；pCR 率相似（32.0% 对 32.6%；调整后 P = 0.924）。在中位随访 3.5 年时，HER2 低分患者与 HER2 IHC 高分 0 分患者的无复发生存期（RFS）在 pCR（调整后 P = 0.368）或 NAT 后残留疾病（RD）（调整后 P = 0.573）之间没有显著差异。pCR患者的远处RFS和总生存期（OS）不因HER2类别而异[远处RFS（DRFS），调整后P = 0.509；OS，调整后P = 0.514]或RD患者的远处RFS和总生存期（OS）不因HER2类别而异（DRFS，调整后P = 0.812；OS，P = 0.285）。在31.1%的HER2 IHC评分为0的病例中，肿瘤HER2状态不一致，HER2表达是在治疗后观察到的；34.8%的HER2低值病例显示出不一致，在RD中没有HER2表达。NAT前后HER2 IHC的不一致可能反映了HER2定量和异质性方面的挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.