PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer

Shi, Qiyun; Xuhong, Juncheng; Luo, Tao; Ge, Jia; Liu, Feng; Yang, Lan; Chen, Qingqiu; Tang, Peng; Fan, Liancheng; Chen, Li; Liang, Yan; Wang, Minghao; Hu, Ying; Zhang, Yi; Bian, Xiu‐Wu; Qi, Xiaowei; Jiang, Jun

doi:10.1038/s41416-022-02021-z

Cited by 11 publications

(17 citation statements)

References 49 publications

(62 reference statements)

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“…[32][33][34] In addition, we previously reported a significant relationship between PIK3CA mutations and lower pCR rate (adjusted p= 0.024) among 425 cancer-related genes assessed by next-generation sequencing of archived tumor blocks from 50 patients enrolled in this clinical trial. 35 This finding is consistent with some previous reports. However, the result was puzzlingly opposite to the findings of NeoATP trial, which reported no statistically significant difference in terms of pCR between subgroups by PIK3CA status (p = 0.958).…”

Section: Discussionsupporting

confidence: 94%

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A multicenter single‐arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2‐positive breast cancer

Shi,

Qi,

Tang

et al. 2023

MedComm

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The objective of this multicenter, single‐arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib (ECPy‐THPy) in the treatment of patients with stage II–III HER2‐positive breast cancer. The present study enrolled patients with stage II–III HER2‐positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21‐day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention‐to‐treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7–75.8%), while the objective response rate was 89.1%. In the post‐hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy‐THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II–III HER2‐positive breast cancer.

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Section: Discussionsupporting

confidence: 94%

“…In addition, we previously reported a significant relationship between PIK3CA mutations and lower pCR rate (adjusted p = 0.024) among 425 cancer‐related genes assessed by next‐generation sequencing of archived tumor blocks from 50 patients enrolled in this clinical trial 35 . This finding is consistent with some previous reports.…”

Section: Discussionsupporting

confidence: 91%

A multicenter single‐arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2‐positive breast cancer

Shi,

Qi,

Tang

et al. 2023

MedComm

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“…We assessed 425 genes in tumor samples from patients receiving neoadjuvant therapy with pyrotinib, trastuzumab, and chemotherapy. We concluded that the PIK3CA mutation was an independent predictor of therapeutic effects; patients with a PIK3CA mutation were less likely to achieve pCR, whereas the TIL level was not associated with pCR [ 85 ]. Those biomarker studies could preliminarily guide the selection of patients more likely to benefit from pyrotinib-based regimens.…”

Section: Clinical Evidence Of Pyrotinib In Early Bcmentioning

confidence: 99%

Pyrotinib-based therapeutic approaches for HER2-positive breast cancer: the time is now

Qi,

Shi,

Xuhong

et al. 2023

Breast Cancer Res

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Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is a highly aggressive subtype associated with poor prognosis. The advent of HER2-targeted drugs, including monoclonal antibodies, tyrosine-kinase inhibitors (TKIs) and antibody–drug conjugates, has yielded improved prognosis for patients. Compared with widely used monoclonal antibodies, small-molecule TKIs have unique advantages including oral administration and favorable penetration of blood–brain barrier for brain metastatic BC, and reduced cardiotoxicity. Pyrotinib is an irreversible TKI of the pan-ErbB receptor, and has recently been shown to be clinically effective for the treatment of HER2-positive BC in metastatic and neoadjuvant settings. This review highlights the development on the application of pyrotinib-based therapeutic approaches in the clinical settings of HER2-positive BC.

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“…In addition, TP53, PIK3CA, and other genetic mutations were reported to affect the efficacy of targeted therapy and prognosis of patients with HER2‐positive BC 9 . It has been reported that HER2‐positive breast cancers with activating mutations in PIK3CA are less likely to benefit from NAT 10,11 . Chemotherapy and radiotherapy cause DNA damage in tumor cells, and TP53 induces apoptosis after DNA damage 12 .…”

Section: Introductionmentioning

confidence: 99%

“… 9 It has been reported that HER2‐positive breast cancers with activating mutations in PIK3CA are less likely to benefit from NAT. 10 , 11 Chemotherapy and radiotherapy cause DNA damage in tumor cells, and TP53 induces apoptosis after DNA damage. 12 Many studies have proven that TP53 mutation can increase the pCR rate of neoadjuvant chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Somatic mutations in a multigene panel and impact on prognosis based on TP53 status in Chinese HER2‐positive patients undergoing neoadjuvant therapy: A single‐institution retrospective cohort

Xiong,

Wang,

Liu

et al. 2024

Cancer Medicine

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BackgroundGene mutations play a crucial role in the occurrence and development of tumors, particularly in breast cancer (BC). Neoadjuvant therapy (NAT) has shown greater clinical benefit in HER2‐positive breast cancer. However, further clinical investigation is needed to fully understand the correlation between genetic mutations and NAT efficacy and the long‐term prognosis in HER2‐positive BC.MethodsThis was a retrospective cohort study of 222 patients receiving NAT between 2017 and 2021 in the Department of Breast Surgery of Fudan University Shanghai Cancer Center. Tumor samples from these patients were subjected to Next Generation Sequencing (NGS) to analyze mutations in 513 cancer‐related genes. This study aimed to investigate the association between these genetic mutations and postoperative pathological complete response (pCR), as well as their impact on disease‐free survival (DFS).ResultsIn total, 48.65% patients reached pCR, ER‐negative status (p < 0.001), PR‐negative status (p < 0.001), Ki67 ≥ 20 (p = 0.011), and dual‐targeted therapy (p < 0.001) were all associated with enhanced pCR rates. The frequency of somatic alterations in TP53 (60%), PIK3CA (15%), and ERBB2 (11%) was highest. In the HER2+/HR‐ cohort, patients who achieved pCR had a significant benefit in prognosis (HR = 3.049, p = 0.0498). KMT2C (p = 0.036) and TP53 (p = 0.037) mutations were significantly increased in patients with DFS events. Moreover, TP53 mutations had prognostic significance in HER2‐positive BC patients with HR‐negative (HR = 3.712, p = 0.027) and pCR (HR = 6.253, p = 0.027) status and who received herceptin‐only targeted therapy (HR = 4.145, p = 0.011).ConclusionsThe genetic mutation profiles of Chinese HER2+ patients who received NAT were discrepant with respect to HR status or DFS events. TP53 mutations have significant prognostic value in patients with NAT for HER2‐positive BC and patients benefit differently depending on HR status, the neoadjuvant regimen and response, which highlights the significance of genetic factors in treatment customization based on individual genetic and clinical characteristics.

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PIK3CA mutations are associated with pathologic complete response rate to neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2-positive breast cancer

Cited by 11 publications

References 49 publications

A multicenter single‐arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2‐positive breast cancer

A multicenter single‐arm trial of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2‐positive breast cancer

Pyrotinib-based therapeutic approaches for HER2-positive breast cancer: the time is now

Somatic mutations in a multigene panel and impact on prognosis based on TP53 status in Chinese HER2‐positive patients undergoing neoadjuvant therapy: A single‐institution retrospective cohort

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