HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis

被引：98

作者：

Tan, Ryan Shea Ying Cong ^{[1
]}

Ong, Whee Sze ^{[2
]}

Lee, Kyung-Hun ^{[3
]}

Lim, Abner Herbert ^{[4
]}

Park, Seri ^{[5
]}

Park, Yeon Hee ^{[5
,6
]}

Lin, Ching-Hung ^{[7
]}

Lu, Yen-Shen ^{[7
]}

Ono, Makiko ^{[8
]}

Ueno, Takayuki ^{[9
]}

Naito, Yoichi ^{[10
]}

Onishi, Tatsuya ^{[11
]}

Lim, Geok-Hoon ^{[12
,13
]}

Tan, Su-Ming ^{[13
,14
]}

Lee, Han-Byoel ^{[15
]}

Ryu, Han Suk ^{[16
]}

Han, Wonshik ^{[15
]}

Tan, Veronique Kiak Mien ^{[13
,17
,18
]}

Wong, Fuh-Yong ^{[19
]}

Im, Seock-Ah ^{[3
]}

Tan, Puay Hoon ^{[20
]}

Chan, Jason Yongsheng ^{[1
,4
,21
]}

Yap, Yoon-Sim ^{[1
,21
]}

机构：

[1] Natl Canc Ctr Singapore, Div Med Oncol, 11 Hosp Crescent, Singapore 169610, Singapore

[2] Natl Canc Ctr Singapore, Div Clin Trials & Epidemiol Sci, Singapore, Singapore

[3] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Internal Med,Seoul Natl Univ Hosp, Seoul, South Korea

[4] Natl Canc Ctr Singapore, Canc Discovery Hub, Singapore, Singapore

[5] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, Seoul, South Korea

[6] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, Seoul, South Korea

[7] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan

[8] Japanese Fdn Canc Res, Canc Inst Hosp, Dept Med Oncol, Tokyo, Japan

[9] Japanese Fdn Canc Res, Canc Inst Hosp, Breast Oncol Ctr, Breast Surg Oncol, Tokyo, Japan

[10] Natl Canc Ctr Hosp East, Dept Med Oncol, Kashiwa, Chiba, Japan

[11] Natl Canc Ctr Hosp East, Dept Breast Surg, Kashiwa, Chiba, Japan

[12] KK Womens & Childrens Hosp, Breast Dept, Singapore, Singapore

[13] Sing Hlth Duke NUS Breast Ctr, Singapore, Singapore

[14] Changi Gen Hosp, Dept Gen Surg, Div Breast Surg, Singapore, Singapore

[15] Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp, Canc Res Inst,Dept Surg, Seoul, South Korea

[16] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Pathol,Seoul Natl Univ Hosp, Seoul, South Korea

[17] Natl Canc Ctr Singapore, Div Surg & Surg Oncol, Singapore, Singapore

[18] Singapore Gen Hosp, Dept Breast Surg, Singapore, Singapore

[19] Natl Canc Ctr Singapore, Div Radiat Oncol, Singapore, Singapore

[20] Singapore Gen Hosp, Div Pathol, Singapore, Singapore

[21] Duke NUS Med Sch, Singapore, Singapore

来源：

BMC MEDICINE | 2022年 / 20卷 / 01期

基金：

英国医学研究理事会;

关键词：

HER2-low breast cancer; ERBB2; neutral; Prognosis; TCGA; METABRIC; CLINICAL ONCOLOGY/COLLEGE; AMERICAN SOCIETY; PROGNOSTIC-FACTOR; IMMUNOHISTOCHEMISTRY; RECOMMENDATIONS; IMPACT; PLUS;

D O I：

10.1186/s12916-022-02284-6

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background HER2-low breast cancer (BC) is currently an area of active interest. This study evaluated the impact of low expression of HER2 on survival outcomes in HER2-negative non-metastatic breast cancer (BC). Methods Patients with HER2-negative non-metastatic BC from 6 centres within the Asian Breast Cancer Cooperative Group (ABCCG) (n = 28,280) were analysed. HER2-low was defined as immunohistochemistry (IHC) 1+ or 2+ and in situ hybridization non-amplified (ISH-) and HER2-zero as IHC 0. Relapse-free survival (RFS) and overall survival (OS) by hormone receptor status and HER2 IHC 0, 1+ and 2+ ISH- status were the main outcomes. A combined TCGA-BRCA and METABRIC cohort (n = 1967) was also analysed to explore the association between HER2 expression, ERBB2 copy number variation (CNV) status and RFS. Results ABCCG cohort median follow-up was 6.6 years; there were 12,260 (43.4%) HER2-low BC and 16,020 (56.6%) HER2-zero BC. The outcomes were better in HER2-low BC than in HER2-zero BC (RFS: centre-adjusted hazard ratio (HR) 0.88, 95% CI 0.82-0.93, P < 0.001; OS: centre-adjusted HR 0.82, 95% CI 0.76-0.89, P < 0.001). On multivariable analysis, HER2-low status was prognostic (RFS: HR 0.90, 95% CI 0.85-0.96, P = 0.002; OS: HR 0.86, 95% CI 0.79-0.93, P < 0.001). These differences remained significant in hormone receptor-positive tumours and for OS in hormone receptor-negative tumours. Superior outcomes were observed for HER2 IHC1+ BC versus HER2-zero BC (RFS: HR 0.89, 95% CI 0.83-0.96, P = 0.001; OS: HR 0.85, 95% CI 0.78-0.93, P = 0.001). No significant differences were seen between HER2 IHC2+ ISH- and HER2-zero BCs. In the TCGA-BRCA and METABRIC cohorts, ERBB2 CNV status was an independent RFS prognostic factor (neutral versus non-neutral HR 0.71, 95% CI 0.59-0.86, P < 0.001); no differences in RFS by ERBB2 mRNA expression levels were found. Conclusions HER2-low BC had a superior prognosis compared to HER2-zero BC in the non-metastatic setting, though absolute differences were modest and driven by HER2 IHC 1+ BC. ERBB2 CNV merits further investigation in HER2-negative BC.

引用

页数：15

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