Comparison of HER2-zero and HER2-low in terms of clinicopathological factors and survival in early-stage breast cancer: A systematic review and meta-analysis

Ergün, Yakup; Uçar, Gökhan; Akagündüz, Baran

doi:10.1016/j.ctrv.2023.102538

Cited by 18 publications

(12 citation statements)

References 48 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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“…25,26 A recent meta-analysis concluded that HER2-low status is associated with enhanced DFS and OS in early-stage BC, regardless of HR status. 27 Furthermore, almost all of these studies demonstrated that HR+ was strongly positively associated with HER2-low expression and lower tumor stage. Denkert et al further indicated that HER2-low expression was correlated with lower Ki67 and lower TP53 levels.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the pCR Rate and DFS Among Breast Cancer Patients with Different Hormone Receptor and HER2 Statuses

Jin¹,

Lan²,

Dai³

et al. 2023

BCTT

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Background: Recent studies have investigated the features of breast cancer (BC) with low human epidermal growth factor receptor 2 (HER2) expression or HER2-0 expression. However, the results were inconsistent. In this study, we investigated the differences in the pathological complete response (pCR) rate and disease-free survival (DFS) between HER2-low and HER2-0 BC patients and between subgroups. Methods: HER2-negative BC patients who received neoadjuvant chemotherapy between January 2013 and December 2019 in our hospital were retrospectively reviewed. First, the pCR rate and DFS were compared between HER2-low and HER2-0 patients and among different hormone receptor (HR) and HER2 statuses. Subsequently, DFS was compared between different HER2 status populations with or without pCR. Finally, a Cox regression model was used to identify the prognostic factors. Results: Overall, 693 patients were selected: 561 were HER2-low, and 132 were HER2-0. Between the two groups, there were significant differences in N stage (P = 0.008) and HR status (P = 0.007). No significant difference in the pCR rate (12.12% vs 14.39%, P = 0.468) or DFS was observed, independent of HR status. HR+/HER2-low patients had a significantly worse pCR rate (P < 0.001) and longer DFS (P < 0.001) than HR-/HER2-low or HER2-0 patients. In addition, a longer DFS was found in HER2-low patients versus HER2-0 patients among those who did not achieve pCR. Cox regression showed that N stage and HR status were prognostic factors in the overall and HER2-low populations, while no prognostic factor was found in the HER2-0 group. Conclusion:This study suggested that HER2 status is not associated with the pCR rate or DFS. Longer DFS was found only among patients who did not achieve pCR in the HER2-low versus HER2-0 population. We speculated that the interaction of HR and HER2 might have played a crucial role in this process.

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“…19 However, a meta-analysis conducted on a cohort of 636,535 patients across 23 studies revealed that the HER2-0 subgroup exhibited a higher prevalence of unfavorable risk factors. 27 Stratification based on HR status demonstrated a correlation between premenopausal status and HER2-0 tumors in the HR-positive subgroup, while young age, grade 3 tumors, and advanced T stage were associated with HER2-0 tumors in the HR-negative subgroup. Additionally, irrespective of HR subtype, HER2-low status exhibited a positive association with improved DFS and OS outcomes across all patients.…”

Section: Her2-0 (Nmentioning

confidence: 86%

“…In HER2‐low tumors, there is a higher prevalence of luminal A and luminal B subtypes compared to HER2‐0 tumors, while the occurrence of basal‐like subtype is lower than that observed in HER2‐0 tumors, thus aligning with the expression of ER 19 . However, a meta‐analysis conducted on a cohort of 636,535 patients across 23 studies revealed that the HER2‐0 subgroup exhibited a higher prevalence of unfavorable risk factors 27 . Stratification based on HR status demonstrated a correlation between premenopausal status and HER2‐0 tumors in the HR‐positive subgroup, while young age, grade 3 tumors, and advanced T stage were associated with HER2‐0 tumors in the HR‐negative subgroup.…”

Section: Discussionmentioning

confidence: 98%

Analysis of clinicopathological characteristics and prognostic factors of early‐stage human epidermal growth factor receptor 2 (HER2)‐low breast cancer: Compared with HER2‐0 breast cancer

Wu,

Yang,

Liu

et al. 2023

Cancer Medicine

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PurposeTo investigate the clinicopathological characteristics and prognostic factors of early‐stage breast cancer (EBC) with human epidermal growth factor receptor 2 (HER2)‐low expression.MethodsThe clinicopathological data and follow‐up information of EBC patients with HER2‐low and HER2‐0 expression treated at the Breast Disease Center of Peking University First Hospital from January 2014 to December 2017 were analyzed. The prognosis between HER2‐low and HER2‐0 expression groups and with different hormone receptor (HR) expression were compared by statistics. Meanwhile, the expression of Ki67, androgen receptor (AR), TOPIIa, P53, PTEN, and CK5/6 were also analyzed with the HER2‐low expression and prognosis.ResultsRetrospectively analyzed 1253 cases of EBC, including 583 (46.5%) cases of HER2‐low breast cancer (BC) and 366 (29.2%) HER2‐0 BC cases. Among the HER2‐low BC patients, 487 (83.5%) were HR‐positive, while 96 (16.5%) were HR‐negative. Among the HER2‐0 BC patients, 265 (72.4%) were HR‐positive, while 101 (27.6%) were HR‐negative. Median follow‐up time was 53 months. The 5‐year disease‐free survival of HER2‐low BC patients was 90.2% (95% confidence interval [CI]: 87.2–93.1), and the 5‐year overall survival was 95.4% (95% CI: 93.3–97.6). Cox regression analysis showed that T stage, lymphovascular invasion, and/or perineural invasion were prognostic factors of HER2‐low BC patients. However, the 5‐year disease‐free survival and overall survival of patients in the HER2‐low and HER2‐0 groups were not significantly different in all patients, but a tendency of better prognosis in HER2‐low group was seen in HR‐negative tumors.ConclusionHER2‐low EBC patients accounted for 46.5% of the patient population. T stage, lymphovascular invasion, and/or perineural invasion were factors affecting the prognosis of BC patients with low HER2 expression. No significant difference in prognosis was noted between HER2‐low and HER2‐0 EBC patients. But in HR‐negative tumors, a tendency of better prognosis was seen in HER2‐low versus HER2‐0.

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Comparison of HER2-zero and HER2-low in terms of clinicopathological factors and survival in early-stage breast cancer: A systematic review and meta-analysis

Cited by 18 publications

References 48 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

Comparison of the pCR Rate and DFS Among Breast Cancer Patients with Different Hormone Receptor and HER2 Statuses

Analysis of clinicopathological characteristics and prognostic factors of early‐stage human epidermal growth factor receptor 2 (HER2)‐low breast cancer: Compared with HER2‐0 breast cancer

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