Targeting the Human Epidermal Growth Factor Receptor Family in Breast Cancer beyond HER2

Witzel, Isabell

doi:10.1159/000510998

Cited by 13 publications

(15 citation statements)

References 43 publications

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“…However, the emergence of the antibody-drug conjugates (ADCs) has provided new treatment decisions for patients with low HER2 expression. Breast cancer classified as negative in a certain proportion (approximately 45-55%) (2)(3)(4) actually belong to the newly proposed HER2-low. Breast cancer with an immunohistochemistry (IHC) score of 1+ or 2+ and unamplified by in situ hybridization (ISH) is referred to as HER2low breast cancer.…”

Section: Introductionmentioning

confidence: 98%

Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer

Shang

Sun

et al. 2023

Front. Oncol.

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BackgroundThe emergence of HER2 antibody-drug conjugates provides new treatment decisions for breast cancer patients, especially those with HER2-low expression. In order to explore the biological characteristics of breast cancer with HER2-low expression, the HER2-low category in primary breast cancer and residual tumor after neoadjuvant therapy was investigated to reflect the evolution of HER2 expression.MethodsHER2 was assessed according to the latest ASCO/CAP guidelines. The cut-off value for staining of HER2-positive cells was >10%. HER2-negative cases were divided into HER2-low (IHC=1+/2+ and no ISH amplification) and HER2-zero (IHC-0), and the clinicopathological characteristics of the cases were collected.ResultsThis study included 1140 patients with invasive breast cancer who received preoperative neoadjuvant therapy from 2018 to 2021, of which 365 patients achieved pCR and 775 were non-pCR. In the non-pCR cohort, HER2-low cases accounted for 59.61% of primary tumors and 55.36% of residual tumors. Among HER2-negative cases, HR-positive tumors had a higher incidence of low HER2 expression compared with triple-negative tumors (80.27% vs 60.00% in primary tumors and 72.68% vs 50.77% in residual tumors). The inconsistency rate of HER2 expression was 21.42%, mainly manifested as the conversion of HER2-low cases to HER2-zero (10.19%) and the conversion of HER2-zero to HER2-low (6.45%). Among the HER2-negative cases in the primary tumor, the HER2 discordance rate of HR-positive cases was lower than that of triple-negative cases (23.34% VS 36.92%). This difference was mainly caused by the case switching from HER2-low to HER2-zero. Compared with HER2-zero cases, there were statistically significant differences in RCB grade, MP grade and the number of metastatic lymph nodes in HER2-low cases. Patients with low HER2 expression had a lower pathological response rate and a higher number of metastatic lymph nodes.ConclusionHER2-low breast cancer is highly unstable during disease evolution and has certain biological characteristics. HER2-low breast cancer is not only correlated with positive HR, but also has a certain correlation with positive AR. Re-detection of HER2 in breast cancer after neoadjuvant therapy may lead to new treatment opportunities for a certain proportion of patients.

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Section: Introductionmentioning

confidence: 98%

Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer

Shang

Sun

et al. 2023

Front. Oncol.

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“…In clinical practice, international guidelines recommend a binary distinction between HER2-positive (HER2+) and HER2-negative (HER2−) BCs, to guide physicians’ treatment decisions [ 6 ]. However, a relevant proportion (≈45–55%) of tumors that are classified as HER2− are in fact what is now called HER2-low [ 7 , 8 , 9 ]. The HER2-low BC subtype represents a new recently proposed nomenclature for those tumors with an immunohistochemistry (IHC) assay score of 1+ or 2+ but with negative in situ hybridization (ISH) assay [ 7 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

HER2-Low Breast Cancer: Molecular Characteristics and Prognosis

Agostinetto

Rediti

Fimereli

et al. 2021

Cancers

149

136

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Background: We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes. Methods: This is a retrospective, observational study of primary BC extracted from The Cancer Genome Atlas dataset. We described the distribution of PAM50 intrinsic subtypes within HER2-low BC subtype according to hormonal receptor status (positive (HR+) and negative (HR−)). Secondly, we assessed the impact of HER2-low on survival outcomes (progression-free interval (PFI), disease-free interval (DFI), and overall survival (OS)). Results: We analyzed 804 primary BCs, including 410 (51%) HER2-low BCs (336 HR+ and 74 HR−). The proportion of HER2-enriched tumors was higher in the HER2-low/HR− group compared to HER2-low/HR+ (13.7% versus 1.2%, respectively). HER2-enriched tumors were more frequent in HER2-low/HR− and HER2-low/HR+ subtypes, compared to HER2-negative/HR− and HER2-negative/HR+ subtypes, respectively (13.7% versus 1.6% and 1.2% versus 0.5%, respectively). We observed no significant differences in PFI, DFI, and OS between HER2-low subtypes and each non-HER2-low subtype paired by HR status. Conclusions: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and ultimately support further investigation of new treatment strategies in the HER2-low category. Moreover, it highlights the importance of considering HR status in the HER2-low category.

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“…In daily clinical practice, therapeutic choice is still driven by the human epidermal growth factor receptor 2 (HER2) and hormone-receptor (HR) status, since gene expression profiling is not routinely available. Although tumors harboring HER2 positivity are characterized by a more aggressive behavior and poorer prognosis than other subtypes, the development of several anti-HER2 targeted agents has dramatically improved the survival outcomes of HER2 positive (HER2+) BC patients, both in early and advanced settings [ 3 , 4 , 5 , 6 , 7 , 8 ]. According to the dichotomic classification proposed by the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, about 80% of breast tumors, lacking HER2 protein overexpression, are classified as HER2 negative (HER2-); within them, approximately 45–55% are characterized by HER2 immunohistochemistry (IHC) assay score of 1+ or 2+ with negative in situ hybridization (ISH), referred to as HER2-low BC [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

HER2-Low Status Does Not Affect Survival Outcomes of Patients with Metastatic Breast Cancer (MBC) Undergoing First-Line Treatment with Endocrine Therapy plus Palbociclib: Results of a Multicenter, Retrospective Cohort Study

Carlino

Diana²,

Ventriglia

et al. 2022

Cancers

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Background: Approximately 45–50% of breast cancers (BCs) have a HER2 immunohistochemical score of 1+ or 2+ with negative in situ hybridization, defining the “HER2-low BC” subtype. No anti-HER2 agents are currently approved for this subgroup in Europe, where treatment is still determined by HR expression status. In this study, we investigated the prognostic significance of HER2-low status in HR+/HER2- metastatic BC (MBC) patients treated with endocrine therapy (ET) plus palbociclib as first line. Methods: We conducted a retrospective study including 252 consecutive HR+/HER2- MBC patients who received first-line ET plus palbociclib at six Italian Oncology Units between March 2016 and June 2021. The chi-square test was used to assess differences in the distribution of clinical and pathological variables between the HER-0 and HER2-low subgroups. Survival outcomes, progression-free survival (PFS) and overall survival (OS), were calculated by the Kaplan–Meier method, and the log-rank test was performed to estimate the differences between the curves. Results: A total of 165 patients were included in the analysis: 94 (57%) and 71 (43%) patients had HER2-0 and HER2-low disease, respectively. The median age at treatment start was 64 years. No correlation between patients and tumor characteristics and HER2 status was found. Median PFS (mPFS) for the entire study cohort was 20 months (95% CI, 18–25 months), while median OS (mOS) was not reached at the time of analysis. No statistically significant differences, in terms of PFS (p = 0.20) and OS (p = 0.1), were observed between HER2-low and HER2-0 subgroups. Conclusions: In our analysis, HR+ MBC patients with low HER2 expression who received first-line treatment with ET plus Palbociclib reported no statistically different survival outcomes compared to HER2-0 patients. Further prospective studies are needed to confirm the clinical role of HER2 expression level.

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Targeting the Human Epidermal Growth Factor Receptor Family in Breast Cancer beyond HER2

Cited by 13 publications

References 43 publications

Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer

Evolution and clinical significance of HER2-low status after neoadjuvant therapy for breast cancer

HER2-Low Breast Cancer: Molecular Characteristics and Prognosis

HER2-Low Status Does Not Affect Survival Outcomes of Patients with Metastatic Breast Cancer (MBC) Undergoing First-Line Treatment with Endocrine Therapy plus Palbociclib: Results of a Multicenter, Retrospective Cohort Study

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