Prognostic effect of low-level HER2 expression in patients with clinically negative HER2 status

Hein, Alexander; Hartkopf, Andreas; Emons, Julius; Lux, Michael P.; Volz, Bernhard; Taran, Florin Andrei; Overkamp, Friedrich; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; Lüftner, Diana; Wurmthaler, Lena A.; Wallwiener, Markus; Müller, Volkmar; Beckmann, Matthias W.; Belleville, Erik; Wimberger, Pauline; Hielscher, Carsten; Kurbacher, Christian M.; Wuerstlein, Rachel; Thomssen, Christoph; Untch, Michael; Fasching, Peter A.; Janni, Wolfgang; Fehm, Tanja; Wallwiener, D.; Brucker, Sara Y.; Schneeweiß, Andreas; Kolberg, Hans‐Christian

doi:10.1016/j.ejca.2021.06.033

Cited by 42 publications

(34 citation statements)

References 33 publications

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“…One trial showed a negative prognostic value of HER2 IHC 2+ only in patients older than 55 years, while there was no OS difference between IHC 2+ and 0 or 1+ tumors in the overall population [ 20 ]. The other two publications did not find any difference in OS between patients with HER2-low tumors compared to patients with completely HER2-negative tumors irrespective of the hormone receptor status [ 21 , 22 ], however the patient numbers in these studies were rather low.…”

Section: Introductionmentioning

confidence: 79%

Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry

et al. 2021

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Background About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody–drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). Patients and methods The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan–Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. Results As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74–1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68–1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. Conclusion Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

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Section: Introductionmentioning

confidence: 79%

Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry

et al. 2021

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“…Several studies indicated that patients with HER2-low tumors experienced poorer survival compared with HER2-zero counterparts ( 7 , 8 , 14 , 15 ), entailing more aggressive treatment. Other studies, however, showed that no significant difference was detected between HER2-zero and HER2-low breast cancer ( 12 , 16 – 18 ). Also, there were studies revealing better survival of HER2-low breast cancer ( 13 , 19 ).…”

Section: Introductionmentioning

confidence: 87%

Clinicopathological Characteristics and Prognosis of HER2-Low Early-Stage Breast Cancer: A Single-Institution Experience

Yun

Wang

et al. 2022

Front. Oncol.

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BackgroundHuman epidermal growth factor 2 (HER2)-low breast cancer, which is defined as HER2 1+ or 2+ in immunohistochemistry without gene amplification, accounts for a considerable part of all breast cancers. However, it remains controversial whether HER2-low breast cancer is a distinct entity. Our aim was to compare the clinicopathological features and survival outcomes between HER2-zero and HER2-low early breast cancer.MethodsThe study was a retrospective analysis that enrolled 1,039 patients with available HER2 expression data in a single institute from 2013 to 2014, of whom 262 HER2-positive patients were excluded from the subsequent analysis. The remaining patients were divided into HER2-zero and HER2-low groups. Each group was further categorized into a hormone receptor (HR)-positive and an HR-negative subgroup. Clinicopathological characteristics were collected and compared between HER2-zero and HER2-low groups. The primary endpoint was disease-free survival (DFS) and overall survival (OS), which were analyzed using the Kaplan–Meier method with log-rank test, landmark analysis, and Cox proportional hazards model.ResultsA total of 777 non-HER2-positive patients were included in this analysis, of whom 126, 552, 53, and 46 patients were HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, and HR-negative/HER2-low, respectively. No significant difference in DFS and OS was detected between the HER2-zero group and the HER2-low group when paired by HR status. Landmark analysis with a time point set at 5 years indicated that HR-positive/HER2-low patients had a better DFS compared with HR-positive/HER2-zero patients after 5 years (p = 0.0047). HER2-low status was an independent prognostic factor for DFS after 5 years [hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.13–0.75, p = 0.01].ConclusionThe clinicopathological characteristics and prognosis of HER2-zero and HER2-low breast cancer were similar regardless of HR status. Patients with HR-positive/HER2-low tumors tended to have a better DFS than their HR-positive/HER2-zero counterparts after 5 years.

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“… 15 On the other hand, other studies have failed to demonstrate any impact of ERBB2 -low status in a metastatic setting. 14 , 16 , 26 In early BC, a study 12 enrolling 2310 patients with ERBB2 -zero early BCs from neoadjuvant trials showed that patients with ERBB2 -low BC had a lower pathological complete response to neoadjuvant chemotherapy compared with patients with ERBB2 -zero tumors (29.2% vs 39.0%; P < .001) suggesting lower chemosensitivity. 12 However, patients with ERBB2 -low tumors had better OS (adjusted HR, 0.64; 95% CI, 0.48-0.86; P = .003).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Management and Outcomes in ERBB2-Low vs ERBB2-Zero Metastatic Breast Cancer in France

et al. 2022

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IMPORTANCE ERBB2-low (ie, ERBB2 immunohistochemistry score of 1+ or 2+ in the absence of ERBB2 gene amplification) breast cancer (BC) is a new entity, with emerging dedicated treatments. Little is known about its prognosis and response to conventional therapy compared with ERBB2-zero breast tumors (ie, those with an immunohistochemistry score of 0). OBJECTIVE To compare the outcomes for patients with ERBB2-low metastatic BC (MBC) with those of patients with ERBB2-zero MBC. DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted from the Epidemiological Strategy and Medical Economics MBC platform and included patients with MBC

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Prognostic effect of low-level HER2 expression in patients with clinically negative HER2 status

Cited by 42 publications

References 33 publications

Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry

Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry

Clinicopathological Characteristics and Prognosis of HER2-Low Early-Stage Breast Cancer: A Single-Institution Experience

Comparison of Management and Outcomes in ERBB2-Low vs ERBB2-Zero Metastatic Breast Cancer in France

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