Kinesin Family Member C1 (KIFC1/HSET): A Potential Actionable Biomarker of Early Stage Breast Tumorigenesis and Progression of High-Risk Lesions

The enigma of why some premalignant or pre-invasive breast lesions transform and progress while others do not remains poorly understood. Currently, no radiologic or molecular biomarkers exist in the clinic that can successfully risk-stratify high-risk lesions for malignant transformation or tumor progression as well as serve as a minimally cytotoxic actionable target for at-risk subpopulations. Breast carcinogenesis involves a series of key molecular deregulatory events that prompt normal cells to bypass tumor-suppressive senescence barriers. Kinesin family member C1 (KIFC1/HSET), which confers survival of cancer cells burdened with extra centrosomes, has been observed in premalignant and pre-invasive lesions, and its expression has been shown to correlate with increasing neoplastic progression. Additionally, KIFC1 has been associated with aggressive breast tumor molecular subtypes, such as basal-like and triple-negative breast cancers. However, the role of KIFC1 in malignant transformation and its potential as a predictive biomarker of neoplastic progression remain elusive. Herein, we review compelling evidence suggesting the involvement of KIFC1 in enabling pre-neoplastic cells to bypass senescence barriers necessary to become immortalized and malignant. We also discuss evidence inferring that KIFC1 levels may be higher in premalignant lesions with a greater inclination to transform and acquire aggressive tumor intrinsic subtypes. Collectively, this evidence provides a strong impetus for further investigation into KIFC1 as a potential risk-stratifying biomarker and minimally cytotoxic actionable target for high-risk patient subpopulations.

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DNA Methylation Patterns in Saliva of Tobacco users with High-Risk Oral Potentially Malignant Disorders

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i32b31754 ◽

2021 ◽

pp. 129-137

Author(s):

Mimansha Patel ◽

Madhuri Nitin Gawande ◽

Minal Shashikant Chaudhary ◽

Alka Harish Hande

Keyword(s):

Dna Methylation ◽

High Risk ◽

Malignant Transformation ◽

Promoter Methylation ◽

Genomic Dna ◽

Premalignant Lesions ◽

Oral Potentially Malignant Disorders ◽

Potentially Malignant Disorders ◽

Potentially Malignant ◽

Methylation Patterns

Background: “Oral Potentially Malignant Disorder (OPMD)” is a well-known symptom that, if untreated, can be carcinogenic. It includes leukoplakia, erythroplakia or erythroleukoplakia. One of the typical premalignant lesions of the oral cavity is “oral leukoplakias (OLs),” which frequently precedes “OSCCs.”OLs with dysplastic characteristics are considered to be at a higher risk of “malignant transformation.” So, early diagnosis of "oral squamous cell carcinomas (OSCCs)" is desperately required to enhance patient prognosis and quality of life (QOL).As a result, we examined the distinctive promoter methylation presence in high-risk OLs. Objectives: To detect, compare & correlate “DNA methylation” patterns in normal individuals, tobacco users without disease and tobacco users with the disease. Methodology: With the participants' full consent, 48 saliva samples were obtained and prepared. DNA isolation, restriction digestion of genomic DNA, extraction of restriction enzyme digested genomic DNA, Polymerase Chain Reaction (PCR), and Agarose Gel Electrophoresis (AGE) were all carried out. Expected results: This study will help us to assess the use of Saliva as an aid to identifying both high and low risk “Oral Potentially Malignant Disorders.” Conclusion: Peculiar promoter methylation of various genes was related to a high possibility of malignant transformation in OLs.

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An Update on Precancerous Lesions of Oral Cavity

International Journal of Medical and Dental Sciences ◽

10.18311/ijmds/2013/19825 ◽

2018 ◽

Vol 2 (1) ◽

pp. 70 ◽

Cited By ~ 2

Author(s):

Deepak Goyal ◽

Pardeep Goyal ◽

Harkanwal Preet Singh ◽

Chanchal Verma

Keyword(s):

Head And Neck Cancer ◽

Survival Rate ◽

High Risk ◽

Oral Cancer ◽

Malignant Transformation ◽

Death Rate ◽

Precancerous Lesions ◽

Correct Diagnosis ◽

Premalignant Lesions ◽

Timely Treatment

Oral cancer is the most common head and neck cancer, found in 270,000 patients annually worldwide. Some cancers develop from precancerous lesions; however, there is no definitive clinico pathological factor or biomarker that reliably enables malignant transformation to be predicted in an individual patient. Early detection and early treatment of oral cancer are important for improving the survival rate of patients; prevention of oral cancer will clearly contribute most to decreasing its death rate. So correct diagnosis and timely treatment of premalignant lesions with high risk of malignant transformation may help to prevent malignant transformation.

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Prospective Validation of a Genomic Assay in Breast Cancer: The 70-gene MammaPrint Assay and the MINDACT Trial

Acta Medica Academica ◽

10.5644/ama2006-124.239 ◽

2019 ◽

Vol 48 (1) ◽

pp. 18

Author(s):

William Audeh ◽

Lisa Blumencranz ◽

Heather Kling ◽

Harsha Trivedi ◽

Gordan Srkalovic

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

High Risk ◽

Expression Analysis ◽

Clinical Utility ◽

Gene Expression Analysis ◽

Early Stage ◽

Significant Proportion ◽

Breast Cancers ◽

Gene Assay

MammaPrint was the first genomic assay in breast cancer to be validated with a prospective randomized trial, the MINDACT trial. The 70 gene MammaPrint assay was developed to determine the risk of distant metastasis in early stage breast cancer through gene expression analysis and was the first FDA cleared genomic assay for breast cancer. The assay identifies primary breast cancers likely to metastasize within the first five years of diagnosis and has clinical utility for helping to determine the expected benefit from adjuvant chemotherapy. The MINDACT Trial was the first trial of a genomic assay in breast cancer to provide prospective, randomized evidence of clinical utility for this important clinical question, identifying a significant proportion of patients who could safely forgo chemotherapy within a cohort of patients with high risk clinical characteristics. Nearly half of all patients (46%) who would have been advised chemotherapy according to clinical guidelines were identified genomically by MammaPrint as being low risk and found to have equivalent rates of freedom from metastasis at 5 years with or without chemotherapy. Based upon the MINDACT trial, the ASCO Biomarker Guidelines now approve the use of MammaPrint to inform decisions regarding chemotherapy for women with clinically high-risk ER+ breast cancer, and as the only approved assay for use in women with 1-3 involved lymph nodes. Recent studies suggest information obtained from the 70-gene assay may also help inform decisions regarding endocrine therapy, as well as chemotherapy, targeted therapy and immunotherapy.Conclusion. The power of gene expression analysis in breast cancer, effectively illustrated with MammaPrint in the MINDACT trial, is now being explored through examination of the full transcriptome in breast cancer.

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Adherence to extended adjuvant endocrine therapy following Breast Cancer Index (BCI) testing in women with early-stage hormone receptor (HR)-positive breast cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.527 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 527-527

Author(s):

Julia Foldi ◽

Catherine A. Schnabel ◽

Max Salganik ◽

Lajos Pusztai ◽

Tara B. Sanft

Keyword(s):

Breast Cancer ◽

High Risk ◽

Endocrine Therapy ◽

Risk Group ◽

Early Stage ◽

Distant Recurrence ◽

Breast Cancers ◽

High Likelihood ◽

Dxa Scans

527 Background: Evidence suggests continuing endocrine therapy (ET) beyond 5 years (yr) may reduce breast cancer recurrence in early stage HR+ breast cancers. Given the modest benefit and potentially serious adverse effects of extended ET (EET), improved approaches to identify patients who are at increased risk of late distant recurrence and who derive benefit from EET are critical. Guidelines recommend shared decision-making between oncologists and patients. The adherence rate to EET by 5 yr is only 50-60%. BCI is a gene-expression assay used to predict late distant recurrence and is predictive of benefit from EET. We assessed adherence to EET in women who had BCI testing. Methods: Women with stage I-III HR+ breast cancer s/p 3.5 yr of adjuvant ET and had BCI testing at our institution (8/2013-7/2015) were included. Pts who had < 4 yr of follow-up since BCI testing were excluded. Information including demographics, tumor characteristics, treatment history, number DXA scans, history of osteopenia/osteoporosis were collected. Data on medication adherence was based on prescriptions in the electronic health record. Results: 102 pts were included in our analysis. The median age was 61yr (46-89 yr). The majority of pts had stage I (63%), N0 (77%) and HER2- (90%) disease. 50 pts (46%) received chemotherapy. 44 (43%) received tamoxifen and 79 (77%) had an aromatase inhibitor. BCI categorized 61 (60%) pts as low risk, 26 (25%) as intermediate, and 15 (15%) as high risk for late distant recurrence. 61 (60%) and 41 (40%) pts were predicted to have low and high likelihood of benefit from EET, respectively. All 15 (100%) pts categorized as high risk for late recurrence were predicted to have a high likelihood to benefit from EET; all were recommended to continue EET by their oncologist and all 15 elected EET. 11 (73%) completed 10 yr or were on EET at last follow-up. Of the 4 (27%) pts who stopped before 10 yr, 1 pt had metastatic recurrence and 3 had intolerable side effects. Pts on EET underwent an avg of 1.91 DXA scans, compared with 1.23 for those who stopped ET at 5 yr (p = 0.003). At a median follow-up of 10 yr from diagnosis, there were 2 metastatic (1/15 in the high risk and 1/26 in the intermediate risk group) and 1 local recurrence (1/61 in the low risk group). Conclusions: In pts who continued ET beyond 5 years based on BCI testing and discussion with their oncologist, the rates of adherence and persistence to EET were higher than those previously published. EET may increase the number of DXA scans performed.

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FEASIBILITY STUDY OF BREAST CANCER RISK MONITORING USING THERMOGRAPHY TECHNIQUE IN MALAYSIA

Jurnal Teknologi ◽

10.11113/jt.v77.6247 ◽

2015 ◽

Vol 77 (7) ◽

Author(s):

Asnida Abd Wahab ◽

Maheza Irna Mohd Salim ◽

Jasmy Yunus

Keyword(s):

Breast Cancer ◽

High Risk ◽

Feasibility Study ◽

Visual Analysis ◽

Early Stage ◽

High Risk Patient ◽

Control Group ◽

Risk Monitoring ◽

Significant Difference ◽

The Government

Breast cancer remains as a serious health issue in Malaysia and most presentation of breast cancer incidences are at the later stage which will reduce the survival rate. Breast Self-Examination for all women (BSE), Clinical Breast Examination for women above 40 years old (CBE) and Mammography for the older and high-risk groups are the current policies that are available in the government hospitals and selected clinics. However, BSE and CBE could not detect the early stage breast cancer while Mammography is less sensitive in detecting tumor in high dense breast tissue. Both factors have caused an increase in the overall percentage of later stage presentation of breast cancer in Malaysia. In this paper, a feasibility study of breast cancer screening and risk monitoring using Thermography technique is presented. Thermography technique is capable in identifying any physiological changes occur prior to lump formation. This technique is simple, cheaper, and produce no radiation which will allow a safe regular screening. In this study, a series of screenings has been performed on carcinogenic induced rats and thermal images acquired were then analyzed for risk monitoring. Visual analysis shown that the presence of hotspot and asymmetrical temperature profile could be an indicator of a high risk patient while temperature measurement on both induced and control groups shows a significant difference in standard deviation of the surface temperature with smaller deviation of 0.31±0.08 observed in control group while bigger deviation of 2.23±0.78 observed in the induced group. Hence, it is shown that Thermography technique could be a potential modality for upfront breast screening in Malaysia.

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Discordant breast cancer: Low risk genomic, high risk pathologic.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18160 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18160-e18160

Author(s):

Leann Blankenship ◽

Daniel Ezekwudo ◽

Ishmael A. Jaiyesimi ◽

Osama Alassi ◽

Michael J. Stender ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

High Risk ◽

Early Stage ◽

Recurrence Score ◽

Low Risk ◽

Partial Mastectomy ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Pathologic Features

e18160 Background: Studies using the 21-gene recurrence score (RS) have shown low risk pathologic features and RS breast cancers do not benefit from systemic chemotherapy (CTx). However, data is lacking for patients with discordant risk factors and which feature, genomic or clinical, plays more of a role in determining outcomes. Methods: Retrospective analysis was conducted to identify breast cancer patients with discordant features, defined as low genomic/high pathologic factors, from 2011 to 2016. Patients were hormone-receptor positive with RS < 18 and had ³ 2 high risk factors: tumor size ³2cm, lymph node (LN) positivity, or grade 2-3 disease. Results: There were 469 patients with low risk RS were identified of whom 118 met discordant risk criteria. Patients management is depicted in Table 1. Of the 118 discordant patients, 22 had breast cancer recurrence as either metastatic (1) or locoregional (21); 11 being ipsilateral while the remainder were contralateral. Patients with ipsilateral recurrences had partial mastectomy and radiotherapy as initial management. CTx was received in 30 patients despite low RS. Recurrences occurred in 31.8% of patients who received adjuvant CTx. The majority of recurrences occurred >5 years after initial diagnosis. Conclusions: Our results show both genomic and pathologic features were important in determining the need for CTx in early stage breast cancer but neither had a greater impact. Thus, we advocate a more comprehensive and individualized approach, taking into account comorbidities, genomic, and pathologic features, for addition of CTx to standard hormonal therapy. Further studies are needed to determine the proper treatment of this unique patient population. [Table: see text]

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Neoadjuvant Chemotherapeutic and Targeted Therapies for Early-stage, High-risk Breast Cancer

European Oncology & Haematology ◽

10.17925/eoh.2014.10.1.28 ◽

2014 ◽

Vol 10 (01) ◽

pp. 28

Author(s):

Clement Chung ◽

Rosetta Lee ◽

◽

Keyword(s):

Breast Cancer ◽

High Risk ◽

Neoadjuvant Therapy ◽

Targeted Therapies ◽

Early Stage ◽

Locally Advanced ◽

Breast Cancers ◽

High Risk Breast Cancer ◽

High Risk Breast ◽

Risk Breast Cancer

Neoadjuvant or preoperative chemotherapy is the preferred treatment for locally advanced, inflammatory and early-stage high-risk breast cancers. Patients with locally advanced breast cancers are candidates for neoadjuvant therapy because their tumours are often not amenable to resection. On the other hand, patients are candidates for neoadjuvant chemotherapy if the breast-conserving surgery is not possible. At present, anthracycline- and taxane-based chemotherapy regimens remain as the cornerstone for neoadjuvant therapy in early breast cancer, but there is a clear need for effective therapies in high-risk, early-stage patients. A number of chemotherapeutic and targeted therapies have been evaluated in clinical trials with varying results. The US Food and Drug Administration (FDA) has recently approved pertuzumab in combination with trastuzumab and cytotoxic chemotherapy as a neoadjuvant therapy option for HER2-positive breast cancer. This article reviews the neoadjuvant chemotherapeutic and targeted therapies options for early-stage, high-risk breast cancer. Possible role of molecular subtyping in triple-negative breast cancer is also described.

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Anesthesia and Perioperative Care of the High-Risk Patient

10.1017/cbo9781139629362 ◽

2014 ◽

Cited By ~ 5

Author(s):

Ian McConachie

Keyword(s):

High Risk ◽

Perioperative Care ◽

High Risk Patient ◽

Risk Patient

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A(H1N1)v cases of the 2009/2010 and 2010/2011 influenza seasons in the Medical and Health Sciences Centre of Debrecen University

Orvosi Hetilap ◽

10.1556/oh.2012.29329 ◽

2012 ◽

Vol 153 (17) ◽

pp. 649-654

Author(s):

Piroska Orosi ◽

Judit Szidor ◽

Tünde Tóthné Tóth ◽

József Kónya

Keyword(s):

High Risk ◽

Influenza Season ◽

National Level ◽

Organ Transplant ◽

High Risk Patient ◽

Risk Groups ◽

Health Sciences ◽

World Health ◽

Transplant Patients ◽

Health Organization

The swine-origin new influenza variant A(H1N1) emerged in 2009 and changed the epidemiology of the 2009/2010 influenza season globally and at national level. Aims: The aim of the authors was to analyse the cases of two influenza seasons. Methods: The Medical and Health Sciences Centre of Debrecen University has 1690 beds with 85 000 patients admitted per year. The diagnosis of influenza was conducted using real-time polymerase chain reaction in the microbiological laboratories of the University and the National Epidemiological Centre, according to the recommendation of the World Health Organization. Results: The incidence of influenza was not higher than that observed in the previous season, but two high-risk patient groups were identified: pregnant women and patients with immunodeficiency (oncohematological and organ transplant patients). The influenza vaccine, which is free for high-risk groups and health care workers in Hungary, appeared to be effective for prevention, because in the 2010/2011 influenza season none of the 58 patients who were administered the vaccination developed influenza. Conclusion: It is an important task to protect oncohematological and organ transplant patients. Orv. Hetil., 2012, 153, 649–654.

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