Prognostic estimates of Ki-67 percentage drop after neoadjuvant chemotherapy (NAC) in luminal B (lumB) and triple negative breast cancer (TNBC)

89 Background: Ki-67 expression in breast cancer has been described as predictive of pathological complete response and prognostic of recurrence free survival (RFS). Our aim was to evaluate in a retrospective cohort of triple negative breast cancer patients if tumor proliferation measured by ki-67 expression is correlated with the outcome. Methods: We evaluated a retrospective cohort of 109 cases of triple negative breast cancer (ER-, PR- and HER2- determined by immunohistochemistry). Ki-67 labeling index was determined in Formalin-Fixed, Paraffin-Embedded residual tumors after neoadjuvant chemotherapy. Patients were stratified in Ki67<15% and Ki67≥15%. Clinicopathological data was retrieved from clinical records. RFS and overall survival (OS) were calculated using the Kaplan–Meier method and variables compared using the log-rank or Breslow test and Hazard Ratios (HR) estimated by the Cox regression. Results: The median age for patients was 47.5 years, 55 (50.5%) were premenopausal and 54 (49.5%) postmenopausal. Eight patients (7.3%) were clinical stages II and 101 (92.7%) stages III. Median of Ki-67 expression was 35.97% (0.96% - 77.7%). There was not association between Ki-67 expression (<15% VS ≥15%) with tumor size, nodal involvement, clinical stage and menopausal status. After a median of follow of 21.6 months, 62 patients (56.9%) have relapsed and 53 (48.6%) have die. The median time for RFS and OS were 21.2 and 31.4 months, respectively. Median of RFS was 12.6 months for Ki67<15% vs 21.2 months for Ki67≥15%, P=0.421 (HR=0.91). Median of OS was 34.9 months for Ki67<15% vs 31.4 months for Ki67≥15%, P=0.755 (HR=1.18). Only nodal involvement was found predictor of shorter RFS (0 nodes, 25.2 months vs 1 -3 nodes, 26.1 months, vs >3 nodes, 9.4 months, P=0.020). Conclusions: Ki-67 labeling index was not related with the outcome in terms of OS and RFS in patients with residual triple negative breast tumors that were treated with neoadjuvant chemotherapy.

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Quantification of Ki67 Change as a Valid Prognostic Indicator of Luminal B Type Breast Cancer After Neoadjuvant Therapy

Pathology & Oncology Research ◽

10.3389/pore.2021.1609972 ◽

2021 ◽

Vol 27 ◽

Author(s):

Shirong Tan ◽

Xin Fu ◽

Shouping Xu ◽

Pengfei Qiu ◽

Zhidong Lv ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Multivariate Analysis ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Survival Outcomes ◽

Luminal B ◽

Medical University ◽

Disease Free

Introduction: Ki67 value and its variation before and after neoadjuvant chemotherapy are commonly tested in relation to breast cancer patient prognosis. This study aims to quantify the extent of changes in Ki67 proliferation pre- and post-neoadjuvant chemotherapy, confirm an optimal cut-off point, and evaluate its potential value for predicting survival outcomes in patients with different molecular subtypes of breast cancer.Methods: This retrospective real-world study recruited 828 patients at the Department of Breast Surgery of the First Affiliated Hospital of China Medical University and the Cancer Hospital of China Medical University from Jan 2014 to Nov 2020. Patient demographic features and disease pathology characteristics were recorded, and biomarkers were verified through immunohistochemistry. Various statistical methods were used to validate the relationships between different characteristics and survival outcomes irrespective of disease-free and overall survival.Results: Among 828 patients, statistically significant effects between pathological complete response and survival outcome were found in both HER2-enriched and triple-negative breast cancer (p < 0.05) but not in Luminal breast cancer (p > 0.05). Evident decrease of Ki67 was confirmed after neoadjuvant chemotherapy. To quantify the extent of Ki67 changes between pre- and post-NAC timepoints, we adopted a computational equation termed ΔKi67% for research. We found the optimal cut-off value to be “ΔKi67% = −63%” via the operating characteristic curve, defining ΔKi67% ≤ −63% as positive status and ΔKi67% > −63% as negative status. Patients with positive ΔKi67% status were 37.1% of the entire cohort. Additionally, 4.7, 39.9, 34.5 and 39.6% of patients with Luminal A, Luminal B, HER2-enriched and triple negative breast cancer were also validated with positive ΔKi67% status. The statistically significant differences between ΔKi67% status and prognostic outcomes were confirmed by univariate and multivariate analysis in Luminal B (univariate and multivariate analysis: p < 0.05) and triple negative breast cancer (univariate and multivariate analysis: p < 0.05). We proved ΔKi67% as a statistically significant independent prognostic factor irrespective of disease-free or overall survival among patients with Luminal B and triple-negative breast cancer.Conclusions:ΔKi67% can aid in predicting patient prognostic outcome, provide a measurement of NAC efficacy, and assist in further clinical decisions, especially for patients with Luminal B breast cancer.

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Predictors of Response and Survival Outcomes of Triple Negative Breast Cancer Receiving Neoadjuvant Chemotherapy

Chemotherapy ◽

10.1159/000509638 ◽

2020 ◽

Vol 65 (3-4) ◽

pp. 101-109

Author(s):

Meizhen Zhu ◽

Yang Yu ◽

Xiying Shao ◽

Liang Zhu ◽

Linbo Wang

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Histological Grade ◽

Disease Free Survival ◽

Complete Response ◽

Survival Outcomes ◽

Ki 67 ◽

Pre Treatment

Background: In triple negative breast cancer (TNBC) patients receiving neoadjuvant chemotherapy (NACT), pre-treatment predictors for pathological complete response (pCR) have been reported; however, those for progressive disease (PD) remain unidentified. Methods: We investigated pre-treatment clinicopathological predictors associated with pCR and PD by retrospectively reviewing data for 165 patients treated between 2015 and 2018. Patients with pCR and PD were compared to those without pCR and PD, respectively, using logistic regression and Kaplan-Meier methods. Results: Lack of androgen receptor (AR) was an independent predictor of pCR, while high histological grade, low Ki-67 index, and incomplete NACT courses were independent predictors of PD. Mean disease-free survival and overall survival were significantly poorer in PD patients than in pCR patients (15.7, 21.3 vs. 52.4, 56.3 months). Conclusions: Insights into the chemo-resistance mechanisms and exploration of novel targeted agents in subgroups as per AR and Ki-67 status are needed to improve survival outcomes in TNBC patients.

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Prognostic Function of Ki-67 for Pathological Complete Response Rate of Neoadjuvant Chemotherapy in Triple-negative Breast Cancer

Tumori Journal ◽

10.1177/030089161410000204 ◽

2014 ◽

Vol 100 (2) ◽

pp. 136-142 ◽

Cited By ~ 3

Author(s):

Guojing Zhang ◽

Wanqing Xie ◽

Zhaozhe Liu ◽

Chao Lin ◽

Ying Piao ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Response Rate ◽

Pathological Complete Response ◽

Complete Response Rate ◽

Complete Response ◽

Ki 67

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Neoadjuvant Chemotherapy of Triple-Negative Breast Cancer: Evaluation of Early Clinical Response, Pathological Complete Response Rates, and Addition of Platinum Salts Benefit Based on Real-World Evidence

Cancers ◽

10.3390/cancers13071586 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1586

Author(s):

Milos Holanek ◽

Iveta Selingerova ◽

Ondrej Bilek ◽

Tomas Kazda ◽

Pavel Fabian ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Real World ◽

Triple Negative ◽

Pathological Complete Response ◽

Complete Response ◽

Ki 67 ◽

Platinum Salts ◽

Real World Evidence

Pathological complete response (pCR) achievement is undoubtedly the essential goal of neoadjuvant therapy for breast cancer, directly affecting survival endpoints. This retrospective study of 237 triple-negative breast cancer (TNBC) patients with a median follow-up of 36 months evaluated the role of adding platinum salts into standard neoadjuvant chemotherapy (NACT). After the initial four standard NACT cycles, early clinical response (ECR) was assessed and used to identify tumors and patients generally sensitive to NACT. BRCA1/2 mutation, smaller unifocal tumors, and Ki-67 ≥ 65% were independent predictors of ECR. The total pCR rate was 41%, the achievement of pCR was strongly associated with ECR (OR = 15.1, p < 0.001). According to multivariable analysis, the significant benefit of platinum NACT was observed in early responders ≥45 years, Ki-67 ≥ 65% and persisted lymph node involvement regardless of BRCA1/2 status. Early responders with pCR had a longer time to death (HR = 0.28, p < 0.001) and relapse (HR = 0.26, p < 0.001). The pCR was achieved in only 7% of non-responders. However, platinum salts favored non-responders’ survival outcomes without statistical significance. Toxicity was significantly often observed in patients with platinum NACT (p = 0.003) but not for grade 3/4 (p = 0.155). These results based on real-world evidence point to the usability of ECR in NACT management, especially focusing on the benefit of platinum salts.

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Patterns of Relapse Related to High Expression of Ki-67 After Neoadjuvant Chemotherapy in Triple Negative Breast Cancer

Journal of Gynecology and Obstetrics ◽

10.11648/j.jgo.20210905.11 ◽

2021 ◽

Vol 9 (5) ◽

pp. 139

Author(s):

Gines Hernandez-Cortes ◽

Javier Hornedo ◽

Raquel Murillo ◽

Ricardo Sainz De La Cuesta ◽

Lucia Gonzalez-Cortijo

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

High Expression ◽

Ki 67

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Avoidance and Period-Shortening of Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer in Stages I and II: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-Type Lesions

Technology in Cancer Research & Treatment ◽

10.1177/1533033820943246 ◽

2020 ◽

Vol 19 ◽

pp. 153303382094324

Author(s):

Koichi Kubouchi ◽

Kyosuke Shimada ◽

Takamichi Yokoe ◽

Yutaka Tsutsumi

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Therapeutic Effect ◽

Triple Negative Breast Cancer ◽

Large Scale ◽

Triple Negative ◽

Poor Responders ◽

Breast Cancers ◽

Ki 67 ◽

Chemotherapy Group

Background: Triple-negative breast cancer encompasses heterogeneous subtypes. Neoadjuvant chemotherapy is ineffective against some triple-negative breast cancers, while others show a favorable prognosis despite chemoresistance. Methods: A total of 51 cases with stages I and II triple-negative breast cancer were analyzed; 34 triple-negative breast cancers treated with neoadjuvant chemotherapy were divided into “good responders” (n = 22), showing therapeutic effect G2b or G3 in surgical specimens, and “poor responders” with therapeutic effect G0, G1a, G1b, and G2a (n = 12). Neoadjuvant chemotherapy was spared in 17 cases (non-neoadjuvant chemotherapy group). Apocrine-type triple-negative breast cancer was defined as triple-negative breast cancer immunoreactive for both androgen receptor and forkhead-box protein A1. Triple-negative breast cancer other than apocrine-type (n = 16) and special types (myoepithelial, medullary, adenoid cystic, and spindle cell carcinomas, n = 6) was categorized as basal-like subtype (n = 29). Prognosis was evaluated in each category. Results: Neoadjuvant chemotherapy provoked significant effects against basal-like triple-negative breast cancer with high Ki-67 labeling (≧50%), and tumor-infiltrating lymphocytes predicted high chemosensitivity. Neoadjuvant chemotherapy was avoidable in triple-negative breast cancer of apocrine- and special types showing low (<50%) Ki-67 labeling. Ten (59%) lesions in the non-neoadjuvant chemotherapy group belonged to the apocrine-type. When clinical complete remission shown by contrast-enhanced magnetic resonance imaging was reached in the course of neoadjuvant chemotherapy against basal-like triple-negative breast cancer, the neoadjuvant chemotherapy period was shortened in 14 (64%) of 22 good responders. Disease-free and overall survival rates were excellent in all groups. Conclusions: The following 2 hypothetical proposals should be proven by large-scale clinical trials. Immunohistochemical recognition of apocrine-type triple-negative breast cancer with low Ki-67 labeling is important for avoiding ineffective/unnecessary neoadjuvant chemotherapy. By employing appropriate clinical imaging, period-shortening is achievable in basal-like triple-negative breast cancer with high Ki-67 labeling.

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