High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

Alba, Emilio; Lluch, Aña; Ribelles, Nuria; Antón-Torres, Antonio; Sánchez‐Rovira, Pedro; Albanell, Joan; Calvo, Lourdes; García-Asenjo, José Antonio López; Palacios, José; Chacón, José Ignacio; Ruı́z, Amparo; Haba-Rodríguez, Juan de la; Seguí-Palmer, Miguel Ángel; Cirauqui, Beatriz; Margelı́, Mireia; Plazaola, Arrate; Barnadas, Agustí; Casas, Maribel; Caballero, Rosalía; Carrasco, Eva; Rojo, Federico

doi:10.1634/theoncologist.2015-0312

Cited by 39 publications

(29 citation statements)

References 45 publications

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“…Ki67 has been used as a marker of such proliferation. Thus, routine assessment has not been recommended when patients receive primary chemotherapy because most data were derived from retrospective studies, and the cutoff points used were selected empirically or were arbitrarily established . It has also been found that patients who experienced progression during NAC had a higher proliferation rate than those who responded to chemotherapy .…”

Section: Discussionmentioning

confidence: 99%

“…High Ki67 expression at baseline is significantly associated with improved pCR rates , primarily in the triple‐negative and HER2‐positive BC subtypes . The potential prognostic value of Ki67 after NAC is less well known .…”

Section: Discussionmentioning

confidence: 99%

“…Cells that are not cycling through S‐phase exhibit a lower Ki67 score . The role of Ki67 as a predictive factor of the response to neoadjuvant hormone therapy has been well established . The majority of studies have identified a high Ki67 proliferation rate as a predictive factor for a higher rate of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) .…”

Section: Introductionmentioning

confidence: 99%

“…Several trials have adopted pCR as a surrogate marker of long‐term treatment efficacy . However, in patients who do not achieve a pCR, other biologic markers should be taken into account in order to establish further prognostic groups and to distinguish patients who might benefit from further adjuvant treatment.…”

Section: Introductionmentioning

confidence: 99%

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Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy

et al. 2018

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This study evaluates the change in Ki67 percentage before and after neoadjuvant chemotherapy (NAC) and its relationship with survival outcomes in patients with breast cancer who did not achieve complete pathological response (pCR). These patients, a heterogeneous group with diverse prognoses that cannot be treated using a single algorithm, pose a challenge to clinicians. This study identified a subgroup of these patients with a poor prognosis, those with luminal B-like tumors without a Ki67 decrease after NAC, thus justifying the introduction of new therapeutic strategies for patients who already present a favorable prognosis (luminal B-like with Ki67 decrease).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy

et al. 2018

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“…Alba et al [21] found that a basal Ki67 proliferation index >0.50 should be considered an independent predictive factor for pCR after neoadjuvant therapy, especially in ER-Her-2- and ER-Her-2+ patients. The study by Baba et al [22 ]showed that strong cytoplasmic NF-κB/p65 expression, but not Ki67 expression, was a prognostic marker for patients with TNBC.…”

Section: Discussionmentioning

confidence: 99%

Significance of Tumor-Infiltrating Lymphocytes and the Expression of Topoisomerase IIα in the Prediction of the Clinical Outcome of Patients with Triple-Negative Breast Cancer after Taxane-Anthracycline-Based Neoadjuvant Chemotherapy

Rao

Qiu²,

et al. 2017

Chemotherapy

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Purpose: The aim of this study was to determine factors able to predict chemotherapeutic responses and clinical outcomes in patients with triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods: Fifty-two TNBC patients on taxane-anthracycline-based NAC were included. The expression of Ki67, topoisomerase IIα (TOPOIIα), and p53, as well as the presence of CD4+ tumor-infiltrating lymphocytes (TILs) and CD8+ TILs were evaluated in biopsy specimens by immunohistochemistry. The expression of Ki67, TOPOIIα, and p53, as well as CD4 and CD8 in TILs was calculated according to the pathological response to NAC, disease-free survival (DFS), and overall survival (OS). Results: Fourteen (26.9%) TNBC patients demonstrated a pathological complete response (pCR). According to univariate analyses, significant factors associated with pCR were high infiltration of CD4+ TILs (p = 0.004), high infiltration of CD8+ TILs (p = 0.010), and high expression of topoisomerase IIα (TOPOIIα) (p = 0.006). CD4+ TILs and TOPOIIα were significantly positively correlated with CD8+ TILs. Multivariate analyses indicated that TOPOIIα was an independent predictor of pCR. Although TNBC patients with high infiltration of CD4+ TILs, CD8+ TILs, or with high expression of TOPOIIα exhibited a significantly good 5-year DFS, only TNBC patients with a high infiltration of CD8+ TILs exhibited significantly positive 5-year OS probabilities. Conclusion: Our study demonstrated that CD4+ TILs and TOPOIIα in pretreated cancer tissues were significantly correlated with CD8+ TILs. CD4+ TILs, CD8+ TILs, and TOPOIIα expression were predictors of pCR and 5-year DFS of TNBC patients who were treated with NAC, and TOPOIIα was an independent predictor of pCR. CD8+ TILs were a key factor in the prediction of good 5-year OS rates of TNBC patients after taxane-anthracycline-based NAC.

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Gene signature‐based prediction of triple‐negative breast cancer patient response to Neoadjuvant chemotherapy

2020

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Neoadjuvant chemotherapy is the current standard of care for large, advanced, and/or inoperable tumors, including triple‐negative breast cancer. Although the clinical benefits of neoadjuvant chemotherapy have been illustrated through numerous clinical trials, more than half of the patients do not experience therapeutic benefit and needlessly suffer from side effects. Currently, no clinically applicable biomarkers are available for predicting neoadjuvant chemotherapy response in triple‐negative breast cancer; the discovery of such a predictive biomarker or marker profile is an unmet need. In this study, we introduce a generic computational framework to calculate a response‐probability score (RPS), based on patient transcriptomic profiles, to predict their response to neoadjuvant chemotherapy. We first validated this framework in ER‐positive breast cancer patients and showed that it predicted neoadjuvant chemotherapy response with equal performance to several clinically used gene signatures, including Oncotype DX and MammaPrint. Then, we applied this framework to triple‐negative breast cancer data and, for each patient, we calculated a response probability score (TNBC‐RPS). Our results indicate that the TNBC‐RPS achieved the highest accuracy for predicting neoadjuvant chemotherapy response compared to previously proposed 143 gene signatures. When combined with additional clinical factors, the TNBC‐RPS achieved a high prediction accuracy for triple‐negative breast cancer patients, which was comparable to the prediction accuracy of Oncotype DX and MammaPrint in ER‐positive patients. In conclusion, the TNBC‐RPS accurately predicts neoadjuvant chemotherapy response in triple‐negative breast cancer patients and has the potential to be clinically used to aid physicians in stratifying patients for more effective neoadjuvant chemotherapy.

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High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

Cited by 39 publications

References 45 publications

Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy

Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy

Significance of Tumor-Infiltrating Lymphocytes and the Expression of Topoisomerase IIα in the Prediction of the Clinical Outcome of Patients with Triple-Negative Breast Cancer after Taxane-Anthracycline-Based Neoadjuvant Chemotherapy

Gene signature‐based prediction of triple‐negative breast cancer patient response to Neoadjuvant chemotherapy

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