This highly heterogeneous disease is characterized by the presence of discrete molecular subtypes with distinct clinical behaviors that can be classified according to gene expression signatures. Findings from numerous studies have demonstrated the prognostic value of measuring Ki in breast cancers. The vast majority of breast cancers are ER positive and can be classified into 2 of the aforementioned molecular subtypes: luminal A and luminal B.
Compared with their luminal B counterparts, luminal A tumors generally are lower grade, have higher expression of estrogen-related genes, have a better prognosis, and are more sensitive to ET.
Distinguishing between these 2 subtypes can guide decisions about the need for added chemotherapy. Because the cost of gene expression analysis has limited its adoption in clinical practice, protein expression levels of ER, progesterone receptor PR , and HER2 determined by IHC analysis can be used as surrogate markers for subtype classification. This highlights a major issue that has hampered the clinical adoption of the Ki index: a multiplicity of assays and lack of standardization in analysis and established cutoffs.
To date, neither the American Society of Clinical Oncology nor the National Comprehensive Cancer Network clinical guidelines on breast cancer recommend using the Ki index because of these issues. The IKWG was established in to develop internationally acceptable standards relating to Ki measurement.
Recently updated recommendations from the group detailed a standardized visual scoring method 2,25 that should be adopted, stressing the importance of quality assurance and quality control programs to maintain the analytical validity of the assay.
Among the controversies surrounding the Ki assay are the multiple counting methods. For tumors with a Ki index between these values, the group recommended using a commercially available multigene expression panel. Neoadjuvant chemotherapy NAC has become standard of care in the treatment of early-stage breast cancer because it promotes achievement of pathological complete response pCR , which correlates with favorable long-term clinical outcomes.
Several studies have looked at baseline levels of Ki as a biomarker for NET and found conflicting results. Although the role of baseline Ki is unclear, these studies have highlighted the powerful potential of the on-treatment Ki index to predict responsiveness to ET and guide decisions about subsequent adjuvant ET.
The Ki index at 2 to 4 weeks after starting NET indicates the level of persistent cell proliferation and resistance or response to ET and is significantly associated with risk of recurrence. The risk was 8. This idea of using on-treatment Ki, alongside other features that predict risk, to triage patients and avoid unnecessary chemotherapy is being prospectively evaluated in several trials.
These data demonstrate that the on-treatment Ki index complements the Oncotype DX RS in selecting patients for whom chemotherapy can be omitted. Meanwhile, endocrine responsiveness was evaluated using the modified Preoperative Endocrine Prognostic Index mPEPI , which incorporates tumor size, number of involved lymph nodes, and on-treatment Ki index.
An mPEPI score of 0 has been shown to be associated with low risk of recurrence without adjuvant chemotherapy. The results indicated that salvage treatment led to very low pCR rates, suggesting that alternative treatment options will be needed for these patients. To help overcome resistance to ET in breast cancer, which occurs almost universally, a number of combination strategies have been explored. Investigators are also exploring whether the Ki index can select patients who might benefit from the addition of a CDKI in this setting.
In the ongoing monarchE trial, patients with high-risk, node-positive, ER-positive, HER2-negative breast cancer are randomized to receive 5 to 10 years of adjuvant ET, with or without the addition of 2 years of the CDKI abemaciclib.
Patients were enrolled in 2 cohorts according to clinicopathologic risk factors cohort 1 or Ki index cohort 2. Investigators are also examining the combination of a CDKI and NET, and in several recent clinical trials, a change in the Ki index from baseline after therapy served as a primary end point. March 24, Jane de Lartigue, PhD. OncologyLive , Vol. Prognostic Marker Most notably, the Ki index has growing importance in breast cancer.
Ki is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat.
J Nat Cancer Inst. Negative controls were accomplished by incubating non-stained sections with buffer solution instead of the primary antibodies.
Duncan correlation was used for analysis of differences between groups. Defining the association between clinical parameters was done using Two-tailed Pearson Chi-square test. This study explored the pathological specimens of women with IDC, aged years mean Twenty-two Triple negativity was observed in 14 The remaining 36 There was a significant inverse relationship of the proliferative index Ki67 with ER On the other hand, no any significant association was found between the proliferative index Ki67 neither with the size of the tumor nor with the number of lymph node involved N Table 2.
ANOVA with pairwise comparison test. The upper numbers in each space represent the type of relationship between Ki67 and the parameter above. If negative means "inverse relationship," if no sign means "direct relationship" while the lower numbers represent the "p" value.
However, no any significant relationship was observed between these two groups regarding Ki67 expression. Similarity between the letters of groups means no difference between them while different letters reflect difference between the groups. The mean Ki67 was higher Among our cases of ductal carcinoma, The triple positive category formed the remaining These findings were close to Onitilo et al study in USA who reported No optimal cutoff point for Ki67 proliferative index has been standardized yet and this may be responsible for the difficulty in choosing a standard threshold for daily practice.
In this study, This finding is similar to that of a previous study conducted in India by Kaur et al. A fact that empower the concept stated Ki is a significant marker considering the proliferative capability of breast cancer cells Luporsi et al. We fail to demonstrate any significant relationship between Ki67 expression neither with tumor size nor with number of lymph nodes involved by metastasis. Here we may say that Ki67 may act as independent prognostic factor, just in contrast to what has been reported by Li et al.
The fact behind this disagreement could be explained by the differences in the Ki67 cut off point. Nishimura et al. Different associations were demonstrated in the literatures Ruiz et al. However, Haroon et al. Similarly, Haroon et al. Furthermore, our study showed a significant association high Ki67 expression and grade-III cancers, suggesting that higher proliferative index reflects hyper-proliferation, poor tumor differentiation and thus worse prognosis.
This finding coincides with results of the Elkablawy et al. In same line, other literature explored the great association between tumor grading and Ki67 index, and thus its prognostic role in BC women Trihia et al. The main limitations of the present study can be declared by the fact that it was a single center study with missing some histopathological parameters, particularly distant metastasis M stage-status in addition to the relatively low Ki67 cut-off value used. In conclusion, this study extended what has been reported previously that besides ER, PR and HER2, the proliferative marker Ki67 can be used in BC as an indicator to obtain prognostic information and may help for therapeutic decisions.
I would like to thank Mr. Osama Alsabawee for his great support in statistical analysis of collected data. National Center for Biotechnology Information , U. Asian Pac J Cancer Prev. Author information Article notes Copyright and License information Disclaimer.
Received Sep 19; Accepted Feb This article has been cited by other articles in PMC. Abstract Background and objectives: To date, many tumor markers have been used to predict prognosis and therapeutic response in patients with breast cancer.
Keywords: Breast cancer, Ki67, immunohistochemistry. Results This study explored the pathological specimens of women with IDC, aged years mean Variable No. Open in a separate window. Diagn Pathol. Correlation between Ki67 and breast cancer prognosis. Ki level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review.
Breast Cancer Research and Treatment. Your Privacy Rights. To change or withdraw your consent choices for VerywellHealth. At any time, you can update your settings through the "EU Privacy" link at the bottom of any page. These choices will be signaled globally to our partners and will not affect browsing data.
We and our partners process data to: Actively scan device characteristics for identification. I Accept Show Purposes. Table of Contents View All. Table of Contents. How it Works. Why It's Used. A Word From Verywell. Breast Cancer Doctor Discussion Guide Get our printable guide for your next healthcare provider's appointment to help you ask the right questions.
Download PDF. Email the Guide Send to yourself or a loved one. Sign Up. Was this page helpful? Thanks for your feedback! What are your concerns? Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles.
Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy. Related Articles. Types of Breast Cancer. How Breast Cancer Is Treated.
0コメント