The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy

BackgroundThe introduction of novel strategies for neoadjuvant therapy (NAT) has significantly enhanced the rate of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC). However, due to tumor heterogeneity, some patients continue to experience poor treatment eff...

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Main Authors: Haoqi Wang, Hongbo Liu, Shan Gao, Lijia Wang, Zihao Bai, Yi Zhang, Peijin Zhang, Fei Liu, Cuizhi Geng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1564693/full
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author Haoqi Wang
Haoqi Wang
Hongbo Liu
Hongbo Liu
Shan Gao
Lijia Wang
Zihao Bai
Yi Zhang
Peijin Zhang
Fei Liu
Fei Liu
Cuizhi Geng
Cuizhi Geng
author_facet Haoqi Wang
Haoqi Wang
Hongbo Liu
Hongbo Liu
Shan Gao
Lijia Wang
Zihao Bai
Yi Zhang
Peijin Zhang
Fei Liu
Fei Liu
Cuizhi Geng
Cuizhi Geng
author_sort Haoqi Wang
collection DOAJ
description BackgroundThe introduction of novel strategies for neoadjuvant therapy (NAT) has significantly enhanced the rate of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC). However, due to tumor heterogeneity, some patients continue to experience poor treatment efficacy, early recurrence, metastasis, and even mortality. Therefore, it is crucial to identify new molecular targets for precise treatment and to develop predictive models for pCR to facilitate tailored therapeutic approaches.MethodsWe conducted a study involving a cohort of TNBC patients who underwent NAT, collecting data on clinicopathological indicators, MRI parameters, and pathological remission outcomes. The expression levels of baseline circular RNA WWC3 (circWWC3) in breast cancer tissue were assessed, and the relationship between its expression and clinicopathological indicators as well as pathological response was analyzed. A nomogram for predicting pCR in TNBC was developed and subsequently validated.ResultsFrom January 2020 to December 2023, a total of 205 patients were included in the final analysis. The rate of total pathological complete response (tpCR), defined as ypT0/is and ypN0, was observed to be 51.7%. CircWWC3 was found to be highly expressed in the cytoplasm, with an expression rate of 79% among all analyzed cancerous tissues. The elevated expression of circWWC3 was positively correlated with T2 stage, N1 status, Ki-67 levels greater than 30%, and moderate to high infiltration of tumor-infiltrating lymphocytes (TILs) (p < 0.05). Additionally, a change rate in the apparent diffusion coefficient (ADC) of breast MRI after two cycles of neoadjuvant therapy (ΔADC 0-2%) greater than 24.53% was significantly associated (p < 0.05). Patients exhibiting high levels of circWWC3 expression were more likely to achieve pCR. Univariate and multivariate regression analyses identified TILs, ΔADC 0-2%, and circWWC3 as key variables for constructing a predictive nomogram for pCR. This model demonstrated strong discrimination, calibration, and clinical applicability.ConclusionElevated expression levels of circWWC3 serve as an independent risk factor influencing the likelihood of achieving a pCR. A predictive model that integrates circWWC3 expression alongside pathological and imaging parameters demonstrates a robust capacity to accurately forecast the probability of pCR in patients diagnosed with TNBC.
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spelling doaj-art-9bcccc073ff64decaa8d23dc7ccf6f3c2025-08-20T03:17:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-07-011510.3389/fonc.2025.15646931564693The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapyHaoqi Wang0Haoqi Wang1Hongbo Liu2Hongbo Liu3Shan Gao4Lijia Wang5Zihao Bai6Yi Zhang7Peijin Zhang8Fei Liu9Fei Liu10Cuizhi Geng11Cuizhi Geng12Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Breast Cancer Molecular Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Breast Cancer Molecular Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaGland Surgery, The Hebei Province People’s Hospital, Shijiazhuang, Hebei, ChinaDepartment of Imaging, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Breast Cancer Molecular Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaResearch Center and Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Breast Cancer Molecular Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaBackgroundThe introduction of novel strategies for neoadjuvant therapy (NAT) has significantly enhanced the rate of pathological complete response (pCR) in patients with triple-negative breast cancer (TNBC). However, due to tumor heterogeneity, some patients continue to experience poor treatment efficacy, early recurrence, metastasis, and even mortality. Therefore, it is crucial to identify new molecular targets for precise treatment and to develop predictive models for pCR to facilitate tailored therapeutic approaches.MethodsWe conducted a study involving a cohort of TNBC patients who underwent NAT, collecting data on clinicopathological indicators, MRI parameters, and pathological remission outcomes. The expression levels of baseline circular RNA WWC3 (circWWC3) in breast cancer tissue were assessed, and the relationship between its expression and clinicopathological indicators as well as pathological response was analyzed. A nomogram for predicting pCR in TNBC was developed and subsequently validated.ResultsFrom January 2020 to December 2023, a total of 205 patients were included in the final analysis. The rate of total pathological complete response (tpCR), defined as ypT0/is and ypN0, was observed to be 51.7%. CircWWC3 was found to be highly expressed in the cytoplasm, with an expression rate of 79% among all analyzed cancerous tissues. The elevated expression of circWWC3 was positively correlated with T2 stage, N1 status, Ki-67 levels greater than 30%, and moderate to high infiltration of tumor-infiltrating lymphocytes (TILs) (p < 0.05). Additionally, a change rate in the apparent diffusion coefficient (ADC) of breast MRI after two cycles of neoadjuvant therapy (ΔADC 0-2%) greater than 24.53% was significantly associated (p < 0.05). Patients exhibiting high levels of circWWC3 expression were more likely to achieve pCR. Univariate and multivariate regression analyses identified TILs, ΔADC 0-2%, and circWWC3 as key variables for constructing a predictive nomogram for pCR. This model demonstrated strong discrimination, calibration, and clinical applicability.ConclusionElevated expression levels of circWWC3 serve as an independent risk factor influencing the likelihood of achieving a pCR. A predictive model that integrates circWWC3 expression alongside pathological and imaging parameters demonstrates a robust capacity to accurately forecast the probability of pCR in patients diagnosed with TNBC.https://www.frontiersin.org/articles/10.3389/fonc.2025.1564693/fulltriple-negative breast cancercircWWC3neoadjuvant therapypathological complete responsenomogram
spellingShingle Haoqi Wang
Haoqi Wang
Hongbo Liu
Hongbo Liu
Shan Gao
Lijia Wang
Zihao Bai
Yi Zhang
Peijin Zhang
Fei Liu
Fei Liu
Cuizhi Geng
Cuizhi Geng
The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy
Frontiers in Oncology
triple-negative breast cancer
circWWC3
neoadjuvant therapy
pathological complete response
nomogram
title The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy
title_full The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy
title_fullStr The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy
title_full_unstemmed The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy
title_short The impact of circWWC3 on neoadjuvant therapy for triple-negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy
title_sort impact of circwwc3 on neoadjuvant therapy for triple negative breast cancer and the construction of a nomogram for predicting pathological complete response after neoadjuvant therapy
topic triple-negative breast cancer
circWWC3
neoadjuvant therapy
pathological complete response
nomogram
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1564693/full
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