M C Liefaard, A van der Voort, M S van Ramshorst, J Sanders, S Vonk, H M Horlings, S Siesling, L de Munck, A E van Leeuwen, M Kleijn, L Mittempergher, M M Kuilman, A M Glas, J Wesseling, E H Lips, G S Sonke
{"title":"BluePrint分子亚型预测her2阳性乳腺癌对新辅助帕妥珠单抗的反应。","authors":"M C Liefaard, A van der Voort, M S van Ramshorst, J Sanders, S Vonk, H M Horlings, S Siesling, L de Munck, A E van Leeuwen, M Kleijn, L Mittempergher, M M Kuilman, A M Glas, J Wesseling, E H Lips, G S Sonke","doi":"10.1186/s13058-023-01664-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.</p><p><strong>Methods: </strong>From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups.</p><p><strong>Results: </strong>BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes.</p><p><strong>Conclusions: </strong>In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.</p>","PeriodicalId":9283,"journal":{"name":"Breast Cancer Research : BCR","volume":"25 1","pages":"71"},"PeriodicalIF":0.0000,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280902/pdf/","citationCount":"0","resultStr":"{\"title\":\"BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer.\",\"authors\":\"M C Liefaard, A van der Voort, M S van Ramshorst, J Sanders, S Vonk, H M Horlings, S Siesling, L de Munck, A E van Leeuwen, M Kleijn, L Mittempergher, M M Kuilman, A M Glas, J Wesseling, E H Lips, G S Sonke\",\"doi\":\"10.1186/s13058-023-01664-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.</p><p><strong>Methods: </strong>From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups.</p><p><strong>Results: </strong>BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes.</p><p><strong>Conclusions: </strong>In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.</p>\",\"PeriodicalId\":9283,\"journal\":{\"name\":\"Breast Cancer Research : BCR\",\"volume\":\"25 1\",\"pages\":\"71\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-06-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10280902/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer Research : BCR\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s13058-023-01664-x\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer Research : BCR","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s13058-023-01664-x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景:帕妥珠单抗的引入大大提高了her2阳性乳腺癌的病理完全缓解(pCR)率，但对长期生存的影响有限，并且不确定哪些患者获益最多。在这项研究中，我们确定了BluePrint亚型在her2阳性乳腺癌中的预后价值。此外，我们评估其作为生物标志物的用途，以预测对含曲妥珠单抗的新辅助化疗有或没有帕妥珠单抗的反应。方法:从一组接受新辅助化疗和曲妥珠单抗联合或不联合帕妥珠单抗治疗的II-III期HER2阳性乳腺癌患者中，选择836例患者进行微阵列基因表达分析，随后读取BluePrint标准(HER2、Basal和Luminal)和双亚型(HER2-single、base -single、Luminal-single、HER2-Basal、Luminal-HER2、Luminal-HER2-Basal)。评估了亚型与病理完全缓解(pCR)、总生存期(OS)和乳腺癌特异性生存期(BCSS)之间的关系，并在BluePrint亚组中评估了帕妥珠单抗的获益。结果:719例患者可获得BluePrint结果。在her2型肿瘤患者中，接受帕妥珠单抗治疗的患者的pCR率为71.9%，而未接受帕妥珠单抗治疗的患者的pCR率为43.5%(校正优势比3.43,95% CI 2.36-4.96)。此外，帕妥珠单抗治疗的OS(校正风险比[aHR] 0.45, 95% CI 0.25-0.80)和BCSS (aHR 0.46, 95% CI 0.24-0.86)的风险均显著降低。her2单一亚组的结果相似。帕妥珠单抗在其他亚型中没有明显的益处。结论:在her2型或her2单型肿瘤患者中，帕妥珠单抗显著提高了pCR率，降低了乳腺癌死亡风险，而在其他亚型中未观察到这一现象。BluePrint亚型可能在未来的研究中有价值，以确定可能对her2靶向药物高度敏感的患者。
BluePrint molecular subtypes predict response to neoadjuvant pertuzumab in HER2-positive breast cancer.
Background: The introduction of pertuzumab has greatly improved pathological complete response (pCR) rates in HER2-positive breast cancer, yet effects on long-term survival have been limited and it is uncertain which patients derive most benefit. In this study, we determine the prognostic value of BluePrint subtyping in HER2-positive breast cancer. Additionally, we evaluate its use as a biomarker for predicting response to trastuzumab-containing neoadjuvant chemotherapy with or without pertuzumab.
Methods: From a cohort of patients with stage II-III HER2-positive breast cancer who were treated with neoadjuvant chemotherapy and trastuzumab with or without pertuzumab, 836 patients were selected for microarray gene expression analysis, followed by readout of BluePrint standard (HER2, Basal and Luminal) and dual subtypes (HER2-single, Basal-single, Luminal-single, HER2-Basal, Luminal-HER2, Luminal-HER2-Basal). The associations between subtypes and pathological complete response (pCR), overall survival (OS) and breast cancer-specific survival (BCSS) were assessed, and pertuzumab benefit was evaluated within the BluePrint subgroups.
Results: BluePrint results were available for 719 patients. In patients with HER2-type tumors, the pCR rate was 71.9% in patients who received pertuzumab versus 43.5% in patients who did not (adjusted Odds Ratio 3.43, 95% CI 2.36-4.96). Additionally, a significantly decreased hazard was observed for both OS (adjusted hazard ratio [aHR] 0.45, 95% CI 0.25-0.80) and BCSS (aHR 0.46, 95% CI 0.24-0.86) with pertuzumab treatment. Findings were similar in the HER2-single subgroup. No significant benefit of pertuzumab was seen in other subtypes.
Conclusions: In patients with HER2-type or HER2-single-type tumors, pertuzumab significantly improved the pCR rate and decreased the risk of breast cancer mortality, which was not observed in other subtypes. BluePrint subtyping may be valuable in future studies to identify patients that are likely to be highly sensitive to HER2-targeting agents.
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