Practical Issues of Ki-67 Evaluation in Breast Cancer Clinical Practice

Hacking, Sean; Wang, Yihong

doi:10.14218/jctp.2022.00012

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…First, any method of assessment needs to be developed following biomarkers standard procedures, including, in particular in this setting, validation in its ability to predict longterm outcomes. Second, currently available biomarkers in this setting, vastly depend on Ki67 which is, as discussed, far from being a reproducible biomarker [29,30,63,64]. Third, multiple gene-expression platforms have demonstrated high utility and reproducibility in ER+/HER2-BC both for molecular subtype and prognosis assessment [32,60].…”

Section: Discussionmentioning

confidence: 99%

“…However, Ki67 evaluation is not a reproducible parameter across laboratories (e.g. The International Ki67 in Breast Cancer Working Group (IKWG) and others do not recommend their use to guide routine clinical care [27,29,30]). Moreover, mPEPI and Ki67 are not independent parameters as PEPI calculation takes into account Ki67 levels, among others [28]).…”

Section: Introductionmentioning

confidence: 99%

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Molecular characterization of the residual disease after neoadjuvant endocrine therapy in ER+/HER2- breast cancer uncovers biomarkers of tumour response

López-Velazco,

Manzano,

Elorriaga

et al. 2024

Preprint

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Background Neoadjuvant endocrine therapy (NET) in oestrogen receptor-positive (ER+) /HER2-negative (HER2-) breast cancer (BC) allows an in vivo evaluation of treatment sensitivity by the monitoring of tumour response and offers the opportunity of personalized BC therapy. However, the lack of reproducible biomarkers to assess response and long-term prognosis after NET, beyond Ki67 levels and preoperative endocrine prognostic index score (mPEPI), is a significant barrier to increase its indications. Methods In this study we searched clinically relevant molecular reporters of NET response and prognosis in a multicentre population of ER+/HER2- BC patients by using: PAM50 gene expression panel, protein evaluation of key proteins involved in tumorigenesis and HER2-Low status evaluation. Results On a cohort of 131 patients our results show that PAM50 categorization (Luminal A vs Luminal B and ROR high vs ROR Low) predicts response to NET, with Luminal A and low ROR score tumours showing better response and prognosis than Luminal B and high ROR score. Moreover, tumours changing from Luminal A to Normal-like after NET presented a significant larger decrease in Ki67 levels at surgery, lower mPEPI score and a lower tumour cellularity size than those with persistent Luminal A status. In addition, we identify that the percentage of p53 positive cells in pre- and post-NET samples are associated with response or prognosis to NET. Conclusion Our findings highlight the change of intrinsic subtype to normal-like after NET as a putative biomarker characterizing a population that benefit highly from NET. If considered conjointly with the pathologic evaluation of response, we could characterize a tumour population benefiting most from endocrine approach and bearing a potential very good prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Molecular characterization of the residual disease after neoadjuvant endocrine therapy in ER+/HER2- breast cancer uncovers biomarkers of tumour response

López-Velazco,

Manzano,

Elorriaga

et al. 2024

Preprint

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“…It has a significantly higher expression in BRCA-positive breast cancer [48,49]. It implies its potential as an efficient prognostic factor in BRCA-positive breast cancer and future therapeutic implications in the context of emerging data suggest it might be advantageous to promote, rather than hinder, cell proliferation for immunotherapy to be optimally effective [50,51].…”

Section: Molecular Subtypes Associationsmentioning

confidence: 99%

Hereditary Breast Cancer in Romania—Molecular Particularities and Genetic Counseling Challenges in an Eastern European Country

et al. 2023

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In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018–2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non-BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

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Antibodies and anti-antibodies specific to estradiol and progesterone and tumor proliferation in breast cancer patients

Glushkov,

Polenok,

Gordeeva

et al. 2024

Sib. onkol. ž.

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The study was aimed to determine the interrelations between levels of serum antibodies specific to estradiol and progesterone (IgA1-E2 and IgA1-Pg) and corresponding antiidiotypic antibodies (IgG2-E2 and IgG2-Pg) and tumor Ki67 positive cells in breast cancer patients (BCP). Material and Methods. The content of these antibodies in the blood serum of BCP (522 at the I stage and 578 at the II –IV stages) was studied using non-competitive enzyme immunoassay. Ki67 was determined using immunohistochemical method. Statistical analysis of the results was performed using the Statistica 8.0 software. Results. There were no revealed the desired associations in BCP I stage. Tumors with high levels of Ki67 positive cells (>20,0 %) were found more often in BCP II –IV stages with high serum levels of IgA1-E2 together with IgA1-Pg than in BCP with low levels of these antibodies (68.8 vs 58.0 %, р=0.02). In contrast, tumors with Ki67>20,0 % were revealed less often in BCP with high levels of IgG2-E2 together with IgG2-Pg (49.6 vs 65.2 %, р=0.002). Tumors with high levels of Ki67 positive cells were revealed in 42.9 % BCP I stage and in 77.1 % BCP II –IV stages with high serum levels of IgA1-E2 and IgA1-Pg in combination with low serum levels of IgG2-E2 and IgG2-Pg (p<0.001). There were no such differences between BCP I and II -IV stages with low levels of IgA1-E2 and IgA1-Pg in combination with high levels of IgG2-E2 and IgG2-Pg (46.7 vs 48.2 %, accordingly, р=0.985). Conclusion. Antibodies against E2 and Pg synergistically promoted, but corresponding antiidiotypic antibodies synergistically inhibited the tumors proliferation in BCP. Immunoassay of antibodies and anti-antibodies to steroids is recommended for research of human hormone-dependent neoplasms progression.

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Practical Issues of Ki-67 Evaluation in Breast Cancer Clinical Practice

Cited by 4 publications

References 19 publications

Molecular characterization of the residual disease after neoadjuvant endocrine therapy in ER+/HER2- breast cancer uncovers biomarkers of tumour response

Molecular characterization of the residual disease after neoadjuvant endocrine therapy in ER+/HER2- breast cancer uncovers biomarkers of tumour response

Hereditary Breast Cancer in Romania—Molecular Particularities and Genetic Counseling Challenges in an Eastern European Country

Antibodies and anti-antibodies specific to estradiol and progesterone and tumor proliferation in breast cancer patients

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