The association between HER2-low expression and prognosis of breast cancer: a systematic review and meta-analysis

Tang, Yuyao; Shen, Guoshuang; Xin, Yuanfang; Li, Zhoujuan; Zheng, Yong Hui; Wang, Miaozhou; Liu, Zhen; Zhao, Yi; Zhao, Fuhua; Ren, Dengfeng; Zhao, Jiuda

doi:10.1177/17588359231156669

Cited by 3 publications

(5 citation statements)

References 42 publications

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“…Some studies found no survival differences comparing patients with ERBB2-low tumors with patients with ERBB2-negative tumors, while others found ERBB2-low to be significant in RFS, BCSM, and OS . However, in several meta-analyses, significant differences were present in clinical outcomes between ERBB2-low and ERBB2-negative tumors . We found significant OS benefit associated with ERBB2-low compared with ERBB2-negative in the hormone receptor–negative BC group (ie, TNBC).…”

Section: Discussioncontrasting

confidence: 46%

“…[23][24][25][26][27][28][29] However, in several meta-analyses, significant differences were present in clinical outcomes between ERBB2-low and ERBB2-negative tumors. [30][31][32][33][34][35] We found significant OS benefit associated with ERBB2-low compared with ERBB2-negative in the hormone receptor-negative BC group (ie, TNBC). We also evaluated the significance of TILs in all subgroups and found that for every 10% increase in TILs, there was a significant increase in the RFS and BCSM in the hormone receptor-negative and ERBB2-low group but not in any other groups, including the hormone receptor-negative and ERBB2-negative group.…”

Section: Jama Network Open | Oncologymentioning

confidence: 74%

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Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer

Khoury,

Mendicino,

Payne Ondracek

et al. 2024

JAMA Netw Open

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ImportanceIt is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative).ObjectiveTo evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study.Design, Setting, and ParticipantsThis cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024.ExposureClinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status.Main Outcome and MeasuresERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC.ResultsOf 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor–negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P = .02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P = .03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P = .01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor–negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P = .009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P = .02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P &lt; .001) compared with patients with ERBB2-negative and hormone receptor–negative tumors. Within the hormone receptor–negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P = .03).Conclusions and RelevanceThese findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.

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Section: Discussioncontrasting

confidence: 46%

Section: Jama Network Open | Oncologymentioning

confidence: 74%

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer

Khoury,

Mendicino,

Payne Ondracek

et al. 2024

JAMA Netw Open

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“…Furthermore, the HER2-low group less frequently had unfavorable risk factors. Lastly, Tang et al analyzed 15 and 9 studies with OS and DFS data and found similar results, including lower pCR rates (HR=0.98, 95% CI=0.96-0.99; p=0.001; and HR=0.96, 95% CI=0.94-0.99; p=0.003) (46).…”

Section: Discussionmentioning

confidence: 75%

Prognostic Value of HER2-low Status in ER+ Early Breast Cancer: A Systematic Review and Meta-Analysis

PETRELLI,

REA,

PARATI

et al. 2023

Anticancer Res

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Background/Aim: Low human epidermal growth factor receptor 2 expression (HER2-low: 1+/2+ by immunohistochemistry without HER2 amplification) is emerging as defining a specific breast cancer (BC) subgroup owing to its distinct biological features. However, its prognostic role has not been confirmed in clinical practice. We conducted a systematic review and meta-analysis to determine the prognostic role of HER2-low status in patients with estrogen receptor-positive (ER+) early BC. Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library for prospective or retrospective studies that reported data on overall (OS) or disease-free (DFS) survival for HER2-low compared to HER2-negative BC. Data were pooled using hazard ratios (HR) with confidence intervals (CI) for OS/DFS of HER2-low vs. HER2-negative subgroups according to the random-effects model. OS was the primary outcome measure, and DFS and pathological complete response were the secondary endpoints. Results: An analysis was made of 25 studies collected, including 34,965 patients with HER2-low BC. A HER2-low status was associated with an HR for OS of 0.83 (95% CI=0.76-0.9, p<0.0.01). Similarly, a pooled HR of 0.89 (95% CI=0.840.94, p<0.0.01) showed that patients with HER2-low BC had an increased DFS. Pathological complete response was significantly lower in p<0.01). Conclusion: Based on these data, HER2-low status should be identified as a potential prognostic factor in early stage ER+ BC. This should be taken into account when considering treatment in (neo)adjuvant settings, and it should be a potential stratification factor in future investigations.

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“…Several recently published systematic reviews and meta-analyses investigated the prognostic significance of HER2-low compared to HER2-zero in early breast cancer ( Table 1 ) [ 13 – 17 ]. A HER2-low status was associated with a better OS in all but one meta-analysis.…”

mentioning

confidence: 99%

“…A HER2-low status was associated with a better OS in all but one meta-analysis. That analysis found no significant association between HER2-low and DFS in the overall population but only in the HR-positive subgroup (HR 0.96, 95% CI 0.94–0.99, P = 0.003) [ 17 ]. In fact, others have confirmed that the association of a HER2-low status with survival is strongest in HR-positive carcinomas [ 15 ].…”

mentioning

confidence: 99%

HER2-low and HER2-zero in breast cancer between prognosis, prediction and entity

Schmidt,

Lehr,

Almstedt

2024

Oncotarget

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The association between HER2-low expression and prognosis of breast cancer: a systematic review and meta-analysis

Cited by 3 publications

References 42 publications

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer

Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer

Prognostic Value of HER2-low Status in ER+ Early Breast Cancer: A Systematic Review and Meta-Analysis

HER2-low and HER2-zero in breast cancer between prognosis, prediction and entity

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