The Role of Ki67 in Evaluating Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer

Zhang, Ailin; Wang, Xiaojing; Fan, Chuifeng; Mao, Xiaoyun

doi:10.3389/fendo.2021.687244

Cited by 54 publications

(47 citation statements)

References 64 publications

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Section: Resultsmentioning

confidence: 99%

“…Ki67 is a nuclear protein that marks active cell proliferation, both in normal and tumoral cells [ 30 ]. Specifically, this protein is used as a marker for the classification, prognosis, and prediction of therapeutic response in breast cancer [ 30 ]. This protein is expressed in all active phases of the cell cycle and decreases its expression after mitosis, in G0 phase [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

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Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action

et al. 2022

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Drug combination and drug repurposing are two strategies that allow to find novel oncological therapies, in a faster and more economical process. In our previous studies, we developed a novel model of drug combination using antineoplastic and different repurposed drugs. We demonstrated the combinations of doxorubicin (DOX) + artesunate, DOX + chloroquine, paclitaxel (PTX) + fluoxetine, PTX + fluphenazine, and PTX + benztropine induce significant cytotoxicity in Michigan Cancer Foundation-7 (MCF-7) breast cancer cells. Furthermore, it was found that 5-FU + thioridazine and 5-fluorouracil (5-FU) + sertraline can synergistically induce a reduction in the viability of human colorectal adenocarcinoma cell line (HT-29). In this study, we aim to (1) evaluate the biosafety profile of these drug combinations for non-tumoral cells and (2) determine their mechanism of action in cancer cells. To do so, human fetal lung fibroblast cells (MRC-5) fibroblast cells were incubated for 48 h with all drugs, alone and in combination in concentrations of 0.25, 0.5, 1, 2, and 4 times their half-maximal inhibitory concentration (IC50). Cell morphology and viability were evaluated. Next, we designed and constructed a cell microarray to perform immunohistochemistry studies for the evaluation of palmitoyl-protein thioesterase 1 (PPT1), Ki67, cleaved-poly (ADP-ribose) polymerase (cleaved-PARP), multidrug resistance-associated protein 2 (MRP2), P-glycoprotein (P-gp), and nuclear factor-kappa-B (NF-kB) p65 expression. We demonstrate that these combinations are cytotoxic for cancer cells and safe for non-tumoral cells at lower concentrations. Furthermore, it is also demonstrated that PPT1 may have an important role in the mechanism of action of these combinations, as demonstrated by their ability to decrease PPT1 expression. These results support the use of antimalarial and central nervous system (CNS) drugs in combination regimens with chemotherapeutic agents; nevertheless, additional studies are recommended to further explore their complete mechanisms of action.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action

et al. 2022

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“…A series of studies demonstrated that Ki67 was highly correlated with poor prognosis in prostate, lung, serous ovarian and pancreatic cancers (21)(22)(23)(24)(25)(26). In breast cancer especially, Ki67 can be used as a determination index for luminal classification and is considered a "therapeutic window" for adjuvant or neoadjuvant therapy (27)(28)(29)(30)(31). A Series of studies on melanoma found a correlation between Ki67 expression and patient prognosis, with increased Ki67 expression being associated with an unfavorable prognosis (17,19,32,33).…”

Section: Discussionmentioning

confidence: 99%

Proliferation Marker Ki67 as a Stratification Index of Adjuvant Chemotherapy for Resectable Mucosal Melanoma

Tang

Wei

et al. 2022

Front. Oncol.

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BackgroundAdjuvant chemotherapy has been shown to produce a favorable prognosis for patients with resectable mucosal melanoma (MM), resulting in the need for stratification to optimally select patients to benefit from adjuvant therapy. This study analyzed Ki67 as a potential stratification index for adjuvant chemotherapy in resectable MM.MethodsPatients with resected MM who received subsequent adjuvant therapy in Beijing Cancer Hospital between 2010 and 2018 were retrospectively enrolled and analyzed. Relapse-free survival (RFS) and melanoma-specific survival (MSS) curves were used to perform the survival comparisons across different subgroups.ResultsFrom Jan 2010 to Dec 2018, 1106 MM patients were screened from a database of 4706 patients and 175 of these patients were finally enrolled. A total of 100 patients received temozolomide (TMZ)-based adjuvant chemotherapy and 75 patients received high-dose interferon-α2b (HDI) adjuvant therapy. Compared with HDI, patients who received TMZ-based adjuvant chemotherapy had significantly superior RFS (21.0 vs. 9.6 months, P = 0.002). For patients with low Ki67 expression (<30%), the two regimens showed no significant difference for impact on RFS (33.9 vs. 22.7 months, P = 0.329). However, for patients with high Ki67 expression (≥30%), TMZ-based adjuvant chemotherapy achieved favorable RFS compared with HDI (18.0 vs. 6.7 months, P < 0.001) and tended to improve MSS compared to HDI (41.4 vs. 25.1 months, P = 0.067).ConclusionCompared with HDI, adjuvant chemotherapy may be more relevant for patients with Ki67 ≥ 30%. Ki67 may serve as a potential index to distinguish populations benefiting from adjuvant chemotherapy in resectable MM, and may provide a basis for stratification in the selection of adjuvant regimens.

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“…This descriptive analysis found that most cases had hormonal and HER2 markers and a very low percentage had the Ki-67 marker, showing that molecular classification data was incomplete. The descriptive analysis also found that ensuring complete molecular classification requires labelling the molecular marker set mandatory data [18][19][20][21][22][23].…”

Section: Quality Of Breast Cancer Data Obtainedmentioning

confidence: 99%

Developing a real-world database for oncology: a descriptive analysis of breast cancer in Argentina

Streich¹,

Villalba²,

Cid³

et al. 2022

ecancer

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Introduction:Registries based on Real-World Data (RWD) are those obtained outside of systematised and randomised clinical trials. They allow the collection of information from a large number of patients and enable the participation of a significant number of professionals. PrecisaXperta is a web platform developed for this purpose with more than 2 years of operation, parameterised for oncology. Its design allows the construction of an epidemiological database in real time and exportable for processing.Objective: To describe the characteristics and operation of this online data recording tool, explain how it was developed and analyse the quality of the information recorded, taking as an example the data obtained for breast cancer.Materials and methods: Physicians, computer scientists and data science analysts participated in the development. Patient data, history, educational level, diagnosis, staging, molecular markers, quality of life, types of treatments, progression and response, imaging, complications, adverse events are some of the fields included. Data treatment in terms of encryption, anonymisation, protection and validation is also explained. The selected breast cancer data for description were processed with medium-level statistical programmes, since the number required to apply Big Data engines is not yet available.Results: From a total of 6,892 solid tumours, 1,892 were breast cancer and 1,654 were selected that complied with a data set minimum elaborated ad hoc. Cases from 13 provinces showed a geolocation bias according to the place of practice of the professionals in the collaborative network. The predominant lack of data was detected in molecular markers (ki67) and correlativity in some lines of treatment. Inconsistencies in dates and therapeutic schemes were also detected. Data curation made it possible to exclude them. The age of the patients was 55.3 ± 11.88 years. At the time of diagnosis, the predominance was in stage I: 36.48% and II 30.06%, with positive hormone receptors in 1,424 (89.96%) cases. The predominant treatments were hormonal (61.54%) and target directed with 30.85% for HER2(+) and 39.14% for HER2(−) accompanied in most cases (85.9%) by some period of chemotherapy. Immunotherapy was much less represented (0.36%). Data were processed, homogenised, pooled and presented and made accessible in a form suitable for application to RWD analyses.Conclusions: PrecisaXperta fulfils this purpose of systematising the information to facilitate its loading with its simple and intuitive interface. From the analysis of the data obtained in breast cancer, it is clear that some fields should be mandatory in order to improve the quality of the information. The results describing the registered breast cancers give us a surface view of the affected population and prepare us to design future studies when we have local Big Data. This type of development, with continuous improvements and online results, will allow with its dissemination, that the participating professionals have information of what happen...

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The Role of Ki67 in Evaluating Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer

Cited by 54 publications

References 64 publications

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action

Combination of Antimalarial and CNS Drugs with Antineoplastic Agents in MCF-7 Breast and HT-29 Colon Cancer Cells: Biosafety Evaluation and Mechanism of Action

Proliferation Marker Ki67 as a Stratification Index of Adjuvant Chemotherapy for Resectable Mucosal Melanoma

Developing a real-world database for oncology: a descriptive analysis of breast cancer in Argentina

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