The Karma research group at Karolinska Institutet is creating the world’s best-characterized breast cancer cohort. The aim is to reduce the mortality and incidence in breast cancer through translational research focusing on breast cancer prevention.


Karma clinical trial on topical endoxifen soon opens for inclusion

The Swedish Medical Products Agency (MPA) has approved a Phase 2 study of topical endoxifen for preventive treatment of women with mammographic breast density. The study, called Karma CREME-1, will be conducted at Stockholm South General Hospital in Sweden and will be led by principal investigator and Karma cohort initiator Dr. Per Hall, MD, Ph.D., Head of the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. The topical endoxifen is developed by Atossa Genetics Inc. The study will open for inclusion by the end of June 2018.


Thesis on aggressive breast cancer based on the Karma study published

On the 23rd of February, Dr Johanna Holm defended her thesis entitled “Aggressive breast cancer: epidemiological studies addressing disease heterogeneity”, partly based on Karma samples. In her thesis, Dr. Holm was seeking to increase our understanding of aggressive breast cancer, and how risk factors may be related to it. Her work highlight that interval breast cancers in women with low mammographic density have the most aggressive phenotype, and also suggest disparate genetic backgrounds of screen-detected breast cancers and interval breast cancer. She also show that women at high risk of breast cancer based on genetic and lifestyle factors were significantly more likely to be diagnosed with breast cancer with a favourable prognosis. Her work emphasises that breast cancer subtypes have different aetiologies and highlight the need to identify risk factors separately for distinct breast cancer subtypes and ages of onset.

Link to Dr. Holms thesis: https://openarchive.ki.se/xmlui/handle/10616/46178?_ga=2.116600580.308538842.1529001747-1483963573.1452614977


Karisma 2 clinical trial on tamoxifen for preventive use is halfway through

The Karisma 2 trial on dose optimisation of tamoxifen for preventive use has now reached 800 participants in Lund and in Stockholm and has thereby reached the halfway through milestone. Karisma 2 in expected to close the inclusion by December 2018.


Karma cohort part of novel discoveries of new genetic breast cancer risk variants

As part of international research consortium including Karma samples, 72 new gene variants that predispose to breast cancer have been identified through an analysis of genetic data from more than 275,000 women, whereof 146,000 with breast cancer. Many of the genes lie in regulatory, rather than coding regions, and some are specific for oestrogen receptor negative breast cancer. “These findings add significantly to our understanding of the inherited basis of breast cancer,” commented Doug Easton, Ph.D., from the University of Cambridge, U.K., one of the lead investigators for the OncoArray consortium, to GEN News. The consortium includes more than 550 researchers at 300 research facilities across the globe.

The OncoArray consortium’s results are published in Nature and in Nature Genetics.

Links to articles in Nature and in Nature Genetics:

https://www.nature.com/articles/nature24284

https://www.nature.com/articles/ng.3785


The first Karma based model for predicting risk of breast cancer has been published

One of the key aims of the Karma Project is to identify the women that eventually will be diagnosed with breast cancer. In collaboration with the Swedish mammography screening program we identified increased levels of mammographic density, microcalcifications and suspicious lumps in the breast as key factors for breast cancer risk. We created a risk model to identify the women who are at high risk after a negative mammography to develop breast cancer until the next mammography visit. In the paper (Eriksson et al, 2017) we show that the high-risk women had a nearly 9-fold increased risk of breast cancer compared to the low risk women. In the full model, also accounting for age of the woman, body-mass-index, use of hormonal replacement therapy, and family history of breast cancer, we identified a small proportion of women who had a very high risk for breast cancer within two years after a regular mammography visit.

The paper was published in Breast Cancer Research, March 2017.

Eriksson M, Czene K, Pawitan Y, Leifland K, Darabi H, Hall P. A clinical model for identifying the short-term risk of breast cancer. Breast Cancer Res. 2017 Mar 14;19(1):29. doi: 10.1186/s13058-017-0820-y. PMID: 28288659

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