Prognostic Value of Receptor Change After Neoadjuvant Chemotherapy in Breast Cancer Patients

Özdemir, Özlem; Zengel, Baha; Cavdar, Demet; Yılmaz, Caner; Durusoy, Raika

doi:10.4274/ejbh.galenos.2022.2022-1-4

Cited by 4 publications

(3 citation statements)

References 28 publications

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“…Discordances in HRs, HER2, tumor grade, and Ki-67 proliferation index can have several clinical significances regarding prognosis, adjuvant treatment, and chemosensitivity or chemoresistance. In terms of prognosis, Ozdemir et al reported that patients having ER- or PR-positive tumors before NACTx and becoming negative in the residual tumors have shorter overall survival than those with an unchanged positive HR status [ 39 ]. However, a receptor status that is negative in the tru-cut biopsy but positive in the residual tumor is challenging and may affect the decision for adjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

Biomarker Discordances and Alterations Observed in Breast Cancer Treated with Neoadjuvant Chemotherapy: Causes, Frequencies, and Clinical Significances

Yılmaz

Cavdar

2022

Current Oncology

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Purpose: Biomarker discordances and alterations can be encountered between tru-cut biopsy and residual tumor in breast cancer treated with neoadjuvant chemotherapy (NACTx). We aimed to investigate the effect of NACTx on major biomarker expression (ER, PR, HER2, Ki-67) and tumor grade, the frequency and causes of receptor discordances, and the clinical significance of changes in terms of adjuvant therapy need and chemosensitivity. Methods: In this retrospective study, ER, PR, HER2, and Ki-67 expression and tumor grades were compared between pre- and post-NACTx tumor samples using the Wilcoxon signed-rank test. The frequencies of receptor discordances and the need for new adjuvant therapy due to discordances were calculated. The effect of patient and tumor characteristics and NACTx regimens on discordances was investigated using multivariate analysis. Using histopathological examinations, residual tumors were divided into chemotherapy-responsive and chemotherapy-unresponsive tumors. Biomarker changes in both groups were analyzed for predictability of chemosensitivity. Results: Of the 169 patients who received NACTx, 102 patients having enough residual tumors in the surgical pathology specimen were enrolled in the study. Histopathologically, about 70% of tumors were partially responsive to NACTx and 30% were unresponsive (chemo-resistant). The concordance and discordance rates were 95.1% versus 4.9% for ER (p = 0.180), 97.1% versus 2.9% for PR (p = 0.083), and 89.2% versus 10.8% for HER2 (p = 0.763), respectively. In addition, 15% of hormone receptor (HR)-negative patients became HR(+) and 5.7% of HER2(−) patients became HER2(+) in the residual tumors, requiring adjuvant endocrine or anti-HER2 therapy. In particular, 18% of triple-negative patients became HR(+) and 12% became HER2(+). HER2 loss was detected in 40% of HER2(+) patients. Multivariate logistic regression analysis revealed that lower estrogen expression (p = 0.046), a smaller tumor size (p = 0.029), and anti-HER2 therapy (p < 0.001) have independent efficacy on ER discordance, PR discordance, and HER2 discordance, respectively. Ki-67 and PR expression significantly decreased in chemotherapy-responsive tumors (p = 0.001 and p = 0.004), and the tumor grade increased in chemotherapy-unresponsive tumors (p = 0.034). Conclusions: Approximately 3–5% of HR discordance and about 10% of HER2 discordance can be observed in breast cancer after currently used NACTx regimens. Discordances are bi-directional (from positive to negative and vice versa), and their causes are multifactorial; they should be assessed accordingly. The NACTx effect alone cannot explain observed discordances but can cause biomarker alterations. The change in receptor status from positive to negative, especially HER2 loss, is mainly associated with the NACTx effect. However, the shift from negative to positive is thought to be primarily related to intratumoral heterogeneity. Receptor statuses becoming positive are of more clinical importance due to adjuvant therapy requirements. Biomarker alterations in PR, Ki-67, and tumor grade can provide predictive information about tumor chemosensitivity.

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Section: Discussionmentioning

confidence: 99%

Biomarker Discordances and Alterations Observed in Breast Cancer Treated with Neoadjuvant Chemotherapy: Causes, Frequencies, and Clinical Significances

Yılmaz

Cavdar

2022

Current Oncology

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“…Because of the relationship between receptor amplification and illness progression, patients with overexpression of the receptor had a poorer prognosis. The expression of Her2/neu and ER/PR status has been proven to be "strongly related in 30% of breast cancers" [115]. This suggests that Her2/neu expression is just as important as ER/PR status.…”

Section: The Her2/neu Receptormentioning

confidence: 99%

Cellular and molecular basis of therapeutic approaches to breast cancer

El‐Tanani

Khatib

Al-Najjar

et al. 2023

Cellular Signalling

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“…A biopsy at diagnosis and post-NAC residual tumors in patients without a pCR can show discrepancies in receptor status (from negative to positive or vice versa) and changes in biomarker expression [ 18 , 19 ]. Discordances in ER, PR, HER2, Ki67, and p53 can indicate chemosensitivity or chemoresistance as well as have clinical implications for the prognosis and adjuvant therapy [ 18 , 20 , 21 , 22 ]. Therefore, changes in biomarkers after NAC were considered in this study.…”

Section: Introductionmentioning

confidence: 99%

Nomograms for Predicting Disease-Free Survival Based on Core Needle Biopsy and Surgical Specimens in Female Breast Cancer Patients with Non-Pathological Complete Response to Neoadjuvant Chemotherapy

Lan

Chen

et al. 2023

JPM

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Purpose: While a pathologic complete response (pCR) is regarded as a surrogate endpoint for positive outcomes in breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC), forecasting the prognosis of non-pCR patients is still an open issue. This study aimed to create and evaluate nomogram models for estimating the likelihood of disease-free survival (DFS) for non-pCR patients. Methods: A retrospective analysis of 607 non-pCR BC patients was conducted (2012–2018). After converting continuous variables to categorical variables, variables entering the model were progressively identified by univariate and multivariate Cox regression analyses, and then pre-NAC and post-NAC nomogram models were developed. Regarding their discrimination, accuracy, and clinical value, the performance of the models was evaluated by internal and external validation. Two risk assessments were performed for each patient based on two models; patients were separated into different risk groups based on the calculated cut-off values for each model, including low-risk (assessed by the pre-NAC model) to low-risk (assessed by the post-NAC model), high-risk to low-risk, low-risk to high-risk, and high-risk to high-risk groups. The DFS of different groups was assessed using the Kaplan–Meier method. Results: Both pre-NAC and post-NAC nomogram models were built with clinical nodal (cN) status and estrogen receptor (ER), Ki67, and p53 status (all p < 0.05), showing good discrimination and calibration in both internal and external validation. We also assessed the performance of the two models in four subtypes, with the triple-negative subtype showing the best prediction. Patients in the high-risk to high-risk subgroup have significantly poorer survival rates (p < 0.0001). Conclusion: Two robust and effective nomograms were developed to personalize the prediction of DFS in non-pCR BC patients treated with NAC.

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Prognostic Value of Receptor Change After Neoadjuvant Chemotherapy in Breast Cancer Patients

Cited by 4 publications

References 28 publications

Biomarker Discordances and Alterations Observed in Breast Cancer Treated with Neoadjuvant Chemotherapy: Causes, Frequencies, and Clinical Significances

Biomarker Discordances and Alterations Observed in Breast Cancer Treated with Neoadjuvant Chemotherapy: Causes, Frequencies, and Clinical Significances

Cellular and molecular basis of therapeutic approaches to breast cancer

Nomograms for Predicting Disease-Free Survival Based on Core Needle Biopsy and Surgical Specimens in Female Breast Cancer Patients with Non-Pathological Complete Response to Neoadjuvant Chemotherapy

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