ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment

Ianza, Anna; Giudici, Fabiola; Pinello, C; Corona, Silvia Paola; Strina, Carla; Bernocchi, Ottavia; Bortul, Marina; Milani, Manuela; Sirico, Marianna; Allevi, Giovanni; Aguggini, Sergio; Cocconi, A.; Azzini, Carlo; Dester, Martina; Cervoni, Valeria; Bottini, Alberto; Cappelletti, Mariarosa; Generali, Daniele

doi:10.1177/1010428320925301

Cited by 9 publications

(10 citation statements)

References 27 publications

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“…Ki67 is considered to be a prognostic and predictive indicator of ER-positive BC, and can be used to predict disease-free and overall survival in BC patients treated with neoadjuvant endocrine therapy. 9 The molecular classification of BC is thus generally based on the single or multiple expressions of HER2, ER, PR, and Ki67. The different biological behaviors and prognoses of different subtypes of BC demonstrate the need to adjust the therapeutic strategies according to the BC subtype.…”

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confidence: 99%

Association Between Contrast‐Enhanced Ultrasound Characteristics and Molecular Subtypes of Breast Cancer

Wen

Kong

Zhang

et al. 2021

J of Ultrasound Medicine

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Objective This study aimed to investigate the correlation between contrast‐enhanced ultrasound (CEUS) features and molecular subtypes of breast cancer (BC). Methods A total of 116 patients (116 lesions) with pathologically diagnosed BC who received conventional ultrasound and CEUS before surgery were enrolled in this study. BC molecular subtypes were identified by postoperative pathological and immunohistochemical analysis as Luminal A (LA), Luminal B (LB), HER2 (H2) over‐expression, and triple‐negative (TN). Qualitative and quantitative CEUS characteristics were analyzed by one‐way analysis of variance (continuous variables) or Pearson's χ2 test or Fisher's exact probability method (categorical variables). Results There were significant differences in enhancement speed and enhancement degree among the four subtypes (P < .05). The area under the curve (AUC), time to peak (TTP), and peak intensity (PI) differed among the four subtypes (P < .05). The AUC of the LA subtype (305.1 ± 188.4) was significantly smaller compared with the H2 (535.7 ± 222.0, P = .007) and TN subtypes (496.6 ± 254.7, P = .019). In addition, TTP was shorter in the H2 subtype (19.8 ± 4.9) compared with the other subtypes, and was significantly shorter than in the LA subtype (26.3 ± 7.2, P = .008) and LB subtype (23.1 ± 6.7, P = .036). The PI of the LA subtype (4.7 ± 2.3) was significantly lower than that of the LB (6.6 ± 2.3, P = .027), H2 (7.4 ± 2.2, P = .005), and TN subtypes (6.9 ± 2.6, P = .014). Conclusions CEUS features differed significantly among different molecular subtypes of BC. The enhancement patterns and parameters may be important predictive features of different subtypes of BC.

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confidence: 99%

Association Between Contrast‐Enhanced Ultrasound Characteristics and Molecular Subtypes of Breast Cancer

Wen

Kong

Zhang

et al. 2021

J of Ultrasound Medicine

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“…Some studies only find significant Ki67 proliferation index differences when comparing pre-NAC with post-surgery in Luminal subtypes [ 37 , 38 ] while other studies have demonstrated that Ki67 reduction also plays a role in TN breast cancer [ 39 , 40 ]. While a separate investigation mentioned

, it only discussed its prognostic role and predictive value within 90 Luminal subtype patients with neoadjuvant letrozole-based treatment without classifying it more broadly [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies indicates that Ki67 levels pre-NAC can be an independent prognostic predictor for OS and DFS [ 12 , 16 ]. Endocrine therapy can decrease cell proliferation, presenting as changed Ki67 level pre- and post-NAC [ 20 , 21 ]. In the POETIC clinical phase-3 trial, this change in Ki67 levels was able to guide endocrine therapy decisions for women with ER-positive breast cancer [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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

Tan¹,

Fu²,

Xu³

et al. 2021

Pathol. Oncol. Res.

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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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“…Similarly, results from the MADONNA study, a multicenter, double-blind, phase II study, revealed a lack of survival advantage upon the addition of sorafenib to docetaxel as first-line treatment in breast cancer patients with metastatic or locally advanced HER2-negative disease (Mavratzas et al, 2019). Recently, Ianza et al showed no difference in survival outcomes for adding sorafenib to letrozole and cyclophosphamide in postmenopausal patients with locally advanced estrogen receptor (ER)-positive, HER2-negative breast cancer in a phase III trial (Ianza et al, 2020). Interestingly, a higher percentage of patients on sorafenib treatment had disease progression (Ianza et al, 2020).…”

Section: Sorafenibmentioning

confidence: 99%

“…Recently, Ianza et al showed no difference in survival outcomes for adding sorafenib to letrozole and cyclophosphamide in postmenopausal patients with locally advanced estrogen receptor (ER)-positive, HER2-negative breast cancer in a phase III trial (Ianza et al, 2020). Interestingly, a higher percentage of patients on sorafenib treatment had disease progression (Ianza et al, 2020). Other clinical studies have constantly supported a lack of survival advantage for the combination of sorafenib and chemotherapy in patients with advanced breast cancer (Gradishar et al, 2013;Luu et al, 2014;Yardley et al, 2016a).…”

Section: Sorafenibmentioning

confidence: 99%

Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches

et al. 2022

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Angiogenesis is a vital process for the growth and dissemination of solid cancers. Numerous molecular pathways are known to drive angiogenic switch in cancer cells promoting the growth of new blood vessels and increased incidence of distant metastasis. Several angiogenesis inhibitors are clinically available for the treatment of different types of advanced solid cancers. These inhibitors mostly belong to monoclonal antibodies or small-molecule tyrosine kinase inhibitors targeting the classical vascular endothelial growth factor (VEGF) and its receptors. Nevertheless, breast cancer is one example of solid tumors that had constantly failed to respond to angiogenesis inhibitors in terms of improved survival outcomes of patients. Accordingly, it is of paramount importance to assess the molecular mechanisms driving angiogenic signaling in breast cancer to explore suitable drug targets that can be further investigated in preclinical and clinical settings. This review summarizes the current evidence for the effect of clinically available anti-angiogenic drugs in breast cancer treatment. Further, major mechanisms associated with intrinsic or acquired resistance to anti-VEGF therapy are discussed. The review also describes evidence from preclinical and clinical studies on targeting novel non-VEGF angiogenic pathways in breast cancer and several approaches to the normalization of tumor vasculature by targeting pericytes, utilization of microRNAs and extracellular tumor-associate vesicles, using immunotherapeutic drugs, and nanotechnology.

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ΔKi67 proliferation index as independent predictive and prognostic factor of outcome in luminal breast cancer: data from neoadjuvant letrozole-based treatment

Cited by 9 publications

References 27 publications

Association Between Contrast‐Enhanced Ultrasound Characteristics and Molecular Subtypes of Breast Cancer

Association Between Contrast‐Enhanced Ultrasound Characteristics and Molecular Subtypes of Breast Cancer

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

Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches

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