Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world
Background: Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic v...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.996434/full |
| _version_ | 1828373595229782016 |
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| author | Serena Di Cosimo Eliana La Rocca Eliana La Rocca Silva Ljevar Maria Carmen De Santis Maria Carmen De Santis Marta Bini Marta Bini Vera Cappelletti Marta Valenti Paolo Baili Filippo G. de Braud Filippo G. de Braud Filippo G. de Braud Secondo Folli Gianfranco Scaperrotta Gianfranco Scaperrotta Chiara Volpi Chiara Volpi Chiara Volpi Andrea Vingiani Andrea Vingiani Andrea Vingiani Claudio Vernieri Claudio Vernieri Claudio Vernieri Paolo Verderio Rosalba Miceli Giancarlo Pruneri Giancarlo Pruneri Giancarlo Pruneri |
| author_facet | Serena Di Cosimo Eliana La Rocca Eliana La Rocca Silva Ljevar Maria Carmen De Santis Maria Carmen De Santis Marta Bini Marta Bini Vera Cappelletti Marta Valenti Paolo Baili Filippo G. de Braud Filippo G. de Braud Filippo G. de Braud Secondo Folli Gianfranco Scaperrotta Gianfranco Scaperrotta Chiara Volpi Chiara Volpi Chiara Volpi Andrea Vingiani Andrea Vingiani Andrea Vingiani Claudio Vernieri Claudio Vernieri Claudio Vernieri Paolo Verderio Rosalba Miceli Giancarlo Pruneri Giancarlo Pruneri Giancarlo Pruneri |
| author_sort | Serena Di Cosimo |
| collection | DOAJ |
| description | Background: Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world.Methods: Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009–2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests.Results: Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0, n = 109), and 1 + or IHC 2+/in situ hybridization negative (HER2-low, n = 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (p = 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%, p < 0.001), well-differentiated (47.5% vs. 26.6%, p = 0.001), less proliferative (21.5% vs. 8.3%, p = 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%, p < 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1–100%) vs. 71.6% (65.9–77.8%) (p = 0.161) in HER2-low and 89.1% (75.8–100%) vs. 72.1% (59.7–87.0%) (p = 0.092) in HER2-0.Conclusion: Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment. |
| first_indexed | 2024-04-14T07:21:08Z |
| format | Article |
| id | doaj.art-c61dcae8ad024a518f451974ec2c145c |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-14T07:21:08Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-c61dcae8ad024a518f451974ec2c145c2022-12-22T02:06:10ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-09-01910.3389/fmolb.2022.996434996434Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real worldSerena Di Cosimo0Eliana La Rocca1Eliana La Rocca2Silva Ljevar3Maria Carmen De Santis4Maria Carmen De Santis5Marta Bini6Marta Bini7Vera Cappelletti8Marta Valenti9Paolo Baili10Filippo G. de Braud11Filippo G. de Braud12Filippo G. de Braud13Secondo Folli14Gianfranco Scaperrotta15Gianfranco Scaperrotta16Chiara Volpi17Chiara Volpi18Chiara Volpi19Andrea Vingiani20Andrea Vingiani21Andrea Vingiani22Claudio Vernieri23Claudio Vernieri24Claudio Vernieri25Paolo Verderio26Rosalba Miceli27Giancarlo Pruneri28Giancarlo Pruneri29Giancarlo Pruneri30Integrated Biology Platform Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyRadiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyClinical Epidemiology and Trial Organization Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyRadiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyRadiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyBiomarkers Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyBiomarkers Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyAnalytic Epidemiology and Health Impact Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalySchool of Medicine, University of Milan, Milan, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyRadiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalySchool of Medicine, University of Milan, Milan, Italy0Department of Pathology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalySchool of Medicine, University of Milan, Milan, Italy0Department of Pathology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalyAnalytic Epidemiology and Health Impact Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy1IFOM ETS - the AIRC Institute of Molecular Oncology, Milan, Italy2Bioinformatics and Biostatistics Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, ItalyClinical Epidemiology and Trial Organization Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyBreast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, ItalySchool of Medicine, University of Milan, Milan, Italy0Department of Pathology, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, ItalyBackground: Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world.Methods: Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009–2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests.Results: Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0, n = 109), and 1 + or IHC 2+/in situ hybridization negative (HER2-low, n = 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (p = 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%, p < 0.001), well-differentiated (47.5% vs. 26.6%, p = 0.001), less proliferative (21.5% vs. 8.3%, p = 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%, p < 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1–100%) vs. 71.6% (65.9–77.8%) (p = 0.161) in HER2-low and 89.1% (75.8–100%) vs. 72.1% (59.7–87.0%) (p = 0.092) in HER2-0.Conclusion: Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment.https://www.frontiersin.org/articles/10.3389/fmolb.2022.996434/fullHER2-lowbreast cancerneoadjuvant chemotherapypredictiveprognostic |
| spellingShingle | Serena Di Cosimo Eliana La Rocca Eliana La Rocca Silva Ljevar Maria Carmen De Santis Maria Carmen De Santis Marta Bini Marta Bini Vera Cappelletti Marta Valenti Paolo Baili Filippo G. de Braud Filippo G. de Braud Filippo G. de Braud Secondo Folli Gianfranco Scaperrotta Gianfranco Scaperrotta Chiara Volpi Chiara Volpi Chiara Volpi Andrea Vingiani Andrea Vingiani Andrea Vingiani Claudio Vernieri Claudio Vernieri Claudio Vernieri Paolo Verderio Rosalba Miceli Giancarlo Pruneri Giancarlo Pruneri Giancarlo Pruneri Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world Frontiers in Molecular Biosciences HER2-low breast cancer neoadjuvant chemotherapy predictive prognostic |
| title | Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world |
| title_full | Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world |
| title_fullStr | Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world |
| title_full_unstemmed | Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world |
| title_short | Moving HER2-low breast cancer predictive and prognostic data from clinical trials into the real world |
| title_sort | moving her2 low breast cancer predictive and prognostic data from clinical trials into the real world |
| topic | HER2-low breast cancer neoadjuvant chemotherapy predictive prognostic |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.996434/full |
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