Karma Intervention Study- Karisma
Karisma (Karma Intervention Study) aims to reduce the incidence of breast cancer by preventing the disease with the medicine tamoxifen. Healthy women who take tamoxifen can have a reduced risk of breast cancer, but the medicine may cause side effects. We want to find out if a lower dose of tamoxifen have fewer side effects without lowering the risk-reducing effect.
As a first step we launch Karisma pilot study to test how tamoxifen affect the so-called mammographic density and whether there is any dose-depending effect. (Pilot study launched March 2015)
Tamoxifen is an antiestrogen which has been used to prevent breast cancer recurrence. Recent studies have shown that tamoxifen also may prevent breast cancer in healthy women. The dose of tamoxifen currently used in the swedish health care is associated with side effects such as hot flushes, sweating and fragile mucous membranes. There is also a risk of more severe side effects.
In Karisma we want to investigate whether a lower dose of tamoxifen, with less risk of side effects, still may have a preventive effect on breast cancer.
To measure the effect of the different doses of tamoxifen, we will study changes in mammographic density, and changes in the spectra of side effects.
The Karisma Pilot study was launched in march 2015. Next roll-out will be in 2016
Karma Kamera- new technique for breast cancer detection
Karma Kamera is the study name of a clinical trial at Södersjukhuset, Stockholm, introducing a new technique developed by Real Imaging (realimaging.com).
Real Imaging’s 3D Functional Metabolic Imaging and Risk Assessment (MIRA) technology is intended to provide a non-invasive non-radiation, and examinee-friendly procedure to determine breast health through the acquisition and analysis of 3D metabolic signatures of the breast. The entire procedure takes approximately 20 minutes.
Since this type of risk assessment provided by the MIRA technology is solely based on biological/metabolic signatures, the MIRA technology might be efficiently used to screen women with dense breast tissue. The imaging dataset are not interpreted by a physician, rather a sophisticated computerized assessment would generate the likelihood for suspicious of cancer. A woman with a positive risk (e.g. suspicious for cancer) would need further imaging workup to diagnose and localize the cancer.
The trial is ongoing and will continue through 2015
Karma Normal – analysis of normal breast tissue
In Karma Normal we want to find out why women with dense breast have a higher risk of developing breast cancer. We want to understand if there are certain properties of the dense breast that predisposes to carcinogenic transformation. This question will be addressed through studying normal breast tissue from healthy women, long before they are diagnosed with breast cancer.
Breast biopsies from women with dense and non-dense breast will be compared. Tissues will be analyzed with a number different methods with the aim of identifying possible explanations for the extremely high breast cancer risk in women with dense breasts.
Karma Normal is performed in collaboration with researchers at Karolinska Institutet and Helsingborgs Lasarett.
Karma Tissue – collection of malignant and normal tissue in Karma participants
Karma participants operated for breast cancer at Södersjukhuset will have their breast cancers examined in detail. Except for the routine analyses, gene expression through RNA sequencing is going to be performed in collaboration with the SCAN-B (http://www.med.lu.se/english/klinvetlund/canceromics/consortia/scan_b) project headed by Professor Åke Borg in Lund. Tissue will be stored fresh frozen and in RNA later. Tissue will be stored in the KI Biobank (http://ki.se/ki/jsp/polopoly.jsp?d=9620&l=en). A number of projects are planned.
The project is performed in collaboration with the surgeons and pathologists at Södersjukhuset and colleagues at University of Lund.
Dr. Fuat Celebioglu – firstname.lastname@example.org
Dr. Eva Darai Ramqvist – email@example.com
Professor Borg Åke – firstname.lastname@example.org
For more information, please contact – Daniel Klevebring – email@example.com
Karma Op – identification of circulating tumor DNA
Cancer cells are of low quality but unfortunately abundant. Tumor RNA is leaking from the cells and is, through DNA sequencing, detectable in plasma. In Karma Op we want to measure the level of circulating tumor DNA in women before and after breast surgery. The aim is to develop methods for monitoring therapy and screening of healthy women.
A pilot was launched in the summer of 2012 and 7 patients were recruited. Whole genome sequencing is currently ongoing and the first results anticipated during 2012.
Karma Op is a cooperative effort between researchers at Karolinska Institutet and Södersjukhuset.
Karma ImageJ – high throughput measurement of mammographic density
The white, dense, part of a mammogram is a reflection of the stroma and epithelial content of the breast. The higher the density, the higher the risk of breast cancer. Breast density can be measured through visual scores or by semi-automatic, computer aided, techniques.
In Karma, more than 3000 mammograms are collected every week and a fully automatic measuring system is therefore a necessity. Using the software ImageJ (http://rsbweb.nih.gov/ij), developed at the National Institute of Health and in collaboration with colleagues at Karolinska Institutet and Agency for Science, Technology and Reserch (A*STAR) in Singapore we are currently developing an automatic measuring device.
An research article has been submitted to Breast Cancer Research and was published July 30, 2012
Karma iCOGS – identification of genetic determinants of breast cancer
Genetic alterations that predispose women for later developing breast cancer are studied in collaboration with the Breast Cancer Association Consortium (BCAC) (http://www.srl.cam.ac.uk/consortia/bcac), the University of Cambridge and the European Commission funded COGS project (http://cogseu.org).
Currently DNA from 6,000 Karma participants, and additional 7,000 Swedish women, is genotyped together with ≈ 220,000 non – Swedish samples. The samples are genotyped with an Illumina Infinum Array chip including 200,000 carefully selected SNPs, the so called iCOGS chip. The first results will be generated during the spring of 2012.
Professor Douglas Easton, head of BCAC – firstname.lastname@example.org
For more information, please contact Professor Per Hall – email@example.com
Karma Risk – individual risk prediction of breast cancer
Through amalgamation of information from the web based Karma questionnaire, mammographic density through Karma ImageJ, and genetic information from Karma iCOGS the individual risk of breast cancer will be calculated. Since not all data is available we are using the current data with the aim of improving the current scoring systems such as the Gail model.
For more information, please contact Hatef Darabi – firstname.lastname@example.org
Karma BOADICEA and TYRER-CUZICK – using family cancer history and lifestyle factors for prediction of breast cancer risk
BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm; http://www.srl.cam.ac.uk/genepi/boadicea/boadicea_intro.html) is a risk model for predicting breast and ovarian cancer. The model estimates probability of carrying BRCA gene mutations and computes age specific risks for breast and ovarian cancer. The model calculates results based on familial cancer history of breast, ovarian, pancreatic, and prostate cancer, as well as BRCA gene test results. The BOADICEA data is collected in the Karma web based questionnaire, which collects data on an unselected population.
TYRER-CUZICK (named after its creators) is a risk model for predicting breast cancer risks for individuals and for the population in general. The model computes age specific risks for breast cancer based on familiy history (in order to calculate mutation gene probability) and lifestyle factors. The risks of developing breast cancer is based on Swedish national incidence-rates for breast cancer and accounts for “competing risk” of non-breast cancer diseases.
For more information, please contact Mikael Eriksson – Mikael.Eriksson@ki.se