Division of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Breast Cancer Res. 2023 Jun 19;25(1):71. doi: 10.1186/s13058-023-01664-x.
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.
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.
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.
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.
曲妥珠单抗的引入极大地提高了 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受益最大。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，我们评估了它作为预测曲妥珠单抗联合新辅助化疗有无 pertuzumab 反应的生物标志物的用途。
从接受新辅助化疗和曲妥珠单抗联合或不联合 pertuzumab 治疗的 II-III 期 HER2 阳性乳腺癌患者队列中，选择了 836 名患者进行微阵列基因表达分析，随后进行 Blueprint 标准（HER2、基底和 Luminal）和双亚型（HER2-单一型、基底-单一型、Luminal-单一型、HER2-基底型、Luminal-HER2 型、Luminal-HER2-基底型）读出。评估了亚型与病理完全缓解（pCR）、总生存（OS）和乳腺癌特异性生存（BCSS）之间的关系，并评估了 pertuzumab 在 Blueprint 亚组中的获益。
Blueprint 结果可用于 719 名患者。在 HER2 型肿瘤患者中，接受 pertuzumab 治疗的患者 pCR 率为 71.9%，而未接受 pertuzumab 治疗的患者为 43.5%（调整后的优势比 3.43，95%CI 2.36-4.96）。此外，观察到 pertuzumab 治疗的 OS（调整后的危险比[aHR]0.45，95%CI 0.25-0.80）和 BCSS（aHR 0.46，95%CI 0.24-0.86）风险显著降低。在 HER2-单一型亚组中发现了类似的结果。在其他亚型中，pertuzumab 无显著获益。
在 HER2 型或 HER2-单一型肿瘤患者中，pertuzumab 显著提高了 pCR 率，并降低了乳腺癌死亡率的风险，而在其他亚型中则没有观察到这一结果。Blueprint 亚型分析可能在未来的研究中具有价值，可以识别出对 HER2 靶向药物高度敏感的患者。
