Irelli Azzurra, Parisi Alessandro, D'Orazio Carla, Sidoni Tina, Rotondaro Silvia, Patruno Leonardo, Pavese Francesco, Bafile Alberto, Resta Valter, Pizzorno Laura, Ciuffetelli Virginia, Dal Mas Antonella, Calvisi Giuseppe, Di Sibio Alessandra, Marzullo Anna, Zelli Veronica, Compagnoni Chiara, Tessitore Alessandra, Alesse Edoardo, Ficorella Corrado, Cortellini Alessio, Cannita Katia
Medical Oncology Unit, Department of Oncology, AUSL 04 Teramo, 64100 Teramo, Italy.
Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Cancers (Basel). 2022 Jun 18;14(12):3003. doi: 10.3390/cancers14123003.
HER2 is considered one of the most traditional prognostic and predictive biomarkers in breast cancer. Literature data confirmed that the addition of pertuzumab to a standard neoadjuvant chemotherapy backbone (either with or without anthracyclines), in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), leads to a higher pathological complete response (pCR) rate, which is known to correlate with a better prognosis. In this retrospective analysis, 47 consecutive patients with HER2-positive EBC received sequential anthracyclines and taxanes plus trastuzumab (ATH) or pertuzumab, trastuzumab and docetaxel (THP). Despite the limited sample size, this monocentric experience highlights the efficacy (in terms of pCR) and safety of THP in the neoadjuvant setting of HER2-positive EBC as an anthracycline-free approach. Given the role of PIK3CA as a prognostic and therapeutic target in breast cancer, tumors were also analyzed to assess the PIK3CA mutational status. Thirty-eight out of forty-seven patients were evaluated, and PIK3CA variants were identified in 21% of tumor samples: overall, one mutation was detected in exon 4 (2.6%), two in exon 9 (5.3%) and four in exon 20 (10.5%). Of note, one sample showed concurrent mutations in exons 9 (codon 545) and 20 (codon 1047). Among patients reaching pCR (n = 13), 38.5% were PIK3CA mutants; on the other hand, among those lacking pCR (n = 25), just 12% showed PIK3CA variants. Regarding THP-treated mutant patients (n = 5), 80% reached pCR (three hormone-receptor-negative, one hormone-receptor-positive). Interestingly, the only patient not achieving pCR had a tumor with two co-occurring PIK3CA mutations. In conclusion, this study provides new evidence about the efficacy and good safety profile of THP, compared to the ATH regimen, as an anthracycline-free neoadjuvant treatment of HER2-positive EBC. Further studies on larger/multicentric cohorts are planned for more in-depth analysis to confirm our molecular and clinical results.
HER2被认为是乳腺癌中最传统的预后和预测生物标志物之一。文献数据证实，对于人表皮生长因子受体2（HER2）阳性早期乳腺癌（EBC）患者，在标准新辅助化疗方案（含或不含蒽环类药物）中加入帕妥珠单抗，可提高病理完全缓解（pCR）率，而pCR率与更好的预后相关。在这项回顾性分析中，47例连续的HER2阳性EBC患者接受了序贯蒽环类药物和紫杉类药物加曲妥珠单抗（ATH）或帕妥珠单抗、曲妥珠单抗和多西他赛（THP）治疗。尽管样本量有限，但这项单中心研究经验突出了THP在HER2阳性EBC新辅助治疗中作为无蒽环类药物方案的疗效（就pCR而言）和安全性。鉴于PIK3CA在乳腺癌中作为预后和治疗靶点的作用，还对肿瘤进行了分析以评估PIK3CA突变状态。47例患者中的38例接受了评估，在21%的肿瘤样本中鉴定出PIK3CA变异：总体而言，在第4外显子中检测到1个突变（2.6%），在第9外显子中检测到2个突变（5.3%），在第20外显子中检测到4个突变（10.5%）。值得注意的是，1个样本在第9外显子（密码子545）和第20外显子（密码子1047）中同时存在突变。在达到pCR的患者（n = 13）中，38.5%为PIK3CA突变体；另一方面，在未达到pCR的患者（n = 25）中，仅有12%显示PIK3CA变异。对于接受THP治疗的突变患者（n = 5），80%达到pCR（3例激素受体阴性，1例激素受体阳性）。有趣的是，唯一未达到pCR的患者肿瘤有两个同时发生的PIK3CA突变。总之，与ATH方案相比，本研究为THP作为HER2阳性EBC的无蒽环类新辅助治疗的疗效和良好安全性提供了新证据。计划对更大规模/多中心队列进行进一步研究以进行更深入分析，以证实我们的分子和临床结果。
