Dataset Information

The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry.

ABSTRACT:

Purpose

The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the main parameters in guiding systemic treatment choices in breast cancer, but can change during the disease course. This study aims to evaluate the biopsy rate and receptor subtype discordance rate in patients diagnosed with advanced breast cancer (ABC).

Methods

Patients diagnosed with ABC in seven hospitals in 2007-2018 were selected from the SOutheast Netherlands Advanced BREast cancer (SONABRE) registry. Multivariable logistic regression analyses were performed to identify factors influencing biopsy and discordance rates.

Results

Overall, 60% of 2854 patients had a biopsy of a metastatic site at diagnosis. One of the factors associated with a reduced biopsy rate was the HR + /HER2 + primary tumor subtype (versus HR + /HER2- subtype: OR = 0.68; 95% CI: 0.51-0.90). Among the 748 patients with a biopsy of the primary tumor and a metastatic site, the overall receptor discordance rate was 18%. This was the highest for the HR + /HER2 + primary tumor subtype, with 55%. In 624 patients with metachronous metastases, the HR + /HER2 + subtype remained the only predictor significantly related to a higher discordance rate, irrespective of prior (neo-)adjuvant therapies (OR = 7.49; 95% CI: 3.69-15.20).

Conclusion

The HR + /HER2 + subtype has the highest discordance rate, but the lowest biopsy rate of all four receptor subtypes. Prior systemic therapy was not independently related to subtype discordance. This study highlights the importance of obtaining a biopsy of metastatic disease, especially in the HR + /HER2 + subtype to determine the most optimal treatment strategy.

SUBMITTER: Meegdes M

PROVIDER: S-EPMC8926963 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry.

Meegdes Marissa M Ibragimova Khava I E KIE Lobbezoo Dorien J A DJA Vriens Ingeborg J H IJH Kooreman Loes F S LFS Erdkamp Frans L G FLG Dercksen M Wouter MW Vriens Birgit E P J BEPJ Aaldering Kirsten N A KNA Pepels Manon J A E MJAE van de Winkel Linda M H LMH Tol Jolien J Heijns Joan B JB van de Wouw Agnes J AJ Peters Natascha A J B NAJB Hochstenbach-Waelen Ananda A Smidt Marjolein L ML Geurts Sandra M E SME Tjan-Heijnen Vivianne C G VCG

Breast cancer research and treatment 20220113 2

<h4>Purpose</h4>The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the main parameters in guiding systemic treatment choices in breast cancer, but can change during the disease course. This study aims to evaluate the biopsy rate and receptor subtype discordance rate in patients diagnosed with advanced breast cancer (ABC).<h4>Methods</h4>Patients diagnosed with ABC in seven hospitals in 2007-2018 were selected from the SOutheast Netherlands Advanced BREast cancer (S ...[more]

PMID: 35025003

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Project description:PurposeImmediate and proper implementation of a new and more potent therapy is important to ensure that the patient achieves the best possible outcome. This study aimed to examine whether the real-world overall survival (OS) has improved in patients with human epidermal growth factor receptor 2-positive (HER2 +) advanced breast cancer (ABC) since the market release of pertuzumab and T-DM1. Furthermore, we aimed to assess the implementation and survival rates per hormone receptor (HR) subtype.Patients and methodsWe included 493 systemically treated patients consecutively diagnosed with HER2 + ABC in 2008-2017 from the SOutheast Netherlands Advanced BREast cancer (SONABRE) Registry. Median OS was obtained using the Kaplan-Meier method and differences between periods (2008-2012 versus 2013-2017) were tested using multivariable Cox proportional hazards regression modeling. The 3-year implementation rates were estimated for any HER2-targeted therapy, pertuzumab, and T-DM1 by using the competing risk method and calculated from the date of diagnosis of ABC to start of HER2-targeted therapy of interest.ResultsThe median OS in 2008-2012 versus 2013-2017 was 28.3 versus 39.7 months in all patients (adjusted hazard ratio (adjHR) 0.85, 95%CI 0.66-1.08), 29.9 versus 36.3 months in patients with HR + /HER2 + disease (adjHR 0.97, 95%CI 0.72-1.32), and 22.7 versus 40.9 months in patients with HR-/HER2 + disease (adjHR 0.59, 95%CI 0.38-0.92). Any HER2-targeted therapy was used in 79% of patients in 2008-2012 and in 84% in 2013-2017. The use of pertuzumab and T-DM1 in 2013-2017 was 48% and 29%, respectively. For patients diagnosed with HR + /HER2 + and HR-/HER2 + disease, implementation rates in 2013-2017 were , respectively, 77% and 99% for any HER2-targeted therapy, 38% and 69% for pertuzumab, and 24% and 40% for T-DM1.ConclusionThe survival of patients with HER2 + ABC improved since the introduction of pertuzumab and T-DM1. There is room for improvement in implementation of these HER2-targeted therapies, especially in patients with HR + /HER2 + disease.

Project description:Summary Background This study aims to evaluate whether changes in therapeutic strategies have improved survival of patients diagnosed with hormone receptor positive (HR+), HER2 negative (HER2−) advanced breast cancer (ABC) in real-world. Methods All 1950 patients systemically treated for HR+/HER2− ABC and diagnosed between 2008 and 2019 in eight hospitals were retrieved from the SONABRE Registry (NCT-03577197). Patients were categorized per three-year cohorts based on year of ABC diagnosis. Tests for trend were used to examine differences in baseline characteristics, Kaplan–Meier methods and Cox proportional hazards for survival analyses, and competing-risk methods for 3-year use of systemic therapy. Findings Over time, patients were older (≥70 years, 37%, n = 169/456 in 2008–2010, 47%, n = 233/493 in 2017–2019, p = 0.004) and more often had multiple metastatic sites at ABC diagnosis (48%, n = 220/456 in 2008–2010, 56%, n = 275/493 in 2017–2019, p = 0.002). Among patients with metachronous metastases the prior exposure to (neo-) adjuvant therapies increased over time (chemotherapy, 38%, n = 138/362 in 2008–2010, 48%, n = 181/376 in 2017–2019, p = <0.001; endocrine therapy, 64%, n = 231/362 in 2008–2010, 72%, n = 271/376 in 2017–2019, p = <0.001). Overall survival significantly improved from median 31.1 months (95% CI:28.2–34.3) for patients diagnosed in 2008–2010 to 38.4 months (95% CI:34.0–41.1) in 2017–2019 (adjusted hazard ratio = 0.76, 95% CI:0.64–0.90; p = 0.001). Three-year use of CDK4/6 inhibitors increased from 0% for patients diagnosed in 2008–2010 to 54% for diagnosis in 2017–2019. Conversely, three-year use of chemotherapy was 50% versus 36%, respectively. Interpretation Over time, patients diagnosed with HR+/HER2− ABC presented with less favourable patient characteristics. Nevertheless, we observed that overall survival of ABC increased between 2008 and 2019, with increased use of endocrine/targeted therapies. Funding The SONABRE Registry is supported by the Netherlands Organization for Health Research and Development (ZonMw: 80-82500-98-8003); 10.13039/100004336Novartis BV; 10.13039/100004337Roche; 10.13039/100004319Pfizer; and 10.13039/100004312Eli Lilly & Co. Funding sources had no role in the writing of the manuscript.

Project description:PURPOSE:HER2 signaling functional activity may be important to measure in addition to HER2 protein quantification when identifying patients eligible for HER2 therapies. A HER2 Signaling Function (CELx HSF) Test for HER2-negative patients uses patient's live tumor cells on a biosensor to identify patients with abnormally high HER2-related signaling (HSFs+) likely to respond to anti-HER2 therapies. METHODS:The CELx HSF test was employed to: (1) characterize the sensitivity and specificity of the test to detect abnormal levels of HER2 signaling; (2) evaluate the inhibitory effectiveness of five different anti-HER2 therapies; (3) assess the correlation between CELx HSF test detection of abnormal HER2 signaling and response to HER2 therapy using xenograft models; and (4) confirm the prevalence of abnormal HER2 signaling amongst HER2-negative breast cancer patients (HER2-/HSFs+). RESULTS:HER2-/HSFs+ breast cancer patient samples were identified and showed sensitivity to five approved anti-HER2 therapies. Xenograft studies using both HER2+ and HER2- cell lines confirmed that CELx HER2 signaling status better predicts HER2 inhibitor efficacy than HER2 receptor status. In a study of 114 HER2-negative breast tumor patient samples, 27 (23.7%; 95% CI = 17-32%) had abnormal HER2 signaling (HSFs+). A ROC curve constructed with this dataset projects the CELx HSF Test would have greater than 90% sensitivity and specificity to detect the HER2-/HSFs+ patient population. CONCLUSIONS:The CELx HSF test is a well-characterized functional biomarker assay capable of identifying dynamic HER2-driven signaling dysfunction in tumor cells from HER2-negative breast cancer patients. This test has demonstrated efficacy of various HER2 targeted therapies in live tumor cells from the HSFs+ population and correlated the test result to HER2 drug response in mouse xenograft studies. The proportion of HER2-negative breast cancer patients found to have abnormal HER2 signaling in a 114 patient sample study, 20-25%, is significant. A clinical trial to evaluate the efficacy of anti-HER2 therapies in this patient population is warranted.

Dataset Information

The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry.

Purpose

Methods

Results

Conclusion

Publications

The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry.

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