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 researchers use exome sequencing of plasma DNA for non-invasive monitoring of tumor burden

Non-invasive monitoring of tumor burden hold great promise for early detection of recurrent breast cancer. Karma researchers recently evaluated and improved exome sequencing to interrogate trace amounts of breast tumors in the plasma of breast cancer patients. “We are encourage by the results”, says Daniel Klevebring, lead author of the study. The researchers are now planning a larger study to investigate the use of exome sequencing of plasma in a primary setting.

Published in PlosOne, Aug 2014. Link to the published paper:

Karma validates volumetric breast density measurement tool

KARMA is the first study validating the performance of a volumetric breast density software (VolparaDensity) in a large-scale setting. Results of the study show that distributions of volumetric density are similar across different vendor platforms and that Volpara breast density is associated with established density determinants and breast cancer risk.

Link to published article:

Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1764-72. doi: 10.1158/1055-9965.EPI-13-1219. Epub 2014 Jul 10. Link to Pubmed:

Karma plans a randomized clinical trial to investigate the effect of different doses of Tamoxifen through measuring the decrease of breast density in healthy women.

Tamoxifen has been used for several years as adjuvant therapy for women diagnosed with breast cancer. Tamoxifen was introduced already in the 1970s and reduces the risk of breast cancer recurrence with approximately 30%. Recent studies also indicate that use of Tamoxifen as primary prevention for healthy women at high risk reduce breast cancer incidence.

Despite the remarkable risk reduction in preventive studies, primary preventive strategies are scarcely part of clinical routine. There are several possible reasons for the reluctance. The major one being that the side effects of these therapies are not trivial. Serious side effects could only be acceptable for those that benefit from therapy, that is, there is a need of identifying women at high risk.

Also, there is not a consensus on dose needed in the preventive setting. So far only full therapeutic dose has been tested and no attempts have been made to determine if lower doses prevent women from being diagnosed with breast cancer.

As a first step toward a larger prospective study the Karma group are now planning to launch a randomized, double-blind, placebo controlled trial to investigate the mammographic density reduction at different doses of Tamoxifen.

Our aim is to identify an optimal Tamoxifen dose for reducing risk of breast cancer. Mammographic density reduction will be used as a proxy for therapy response and thereby indirectly incidence.

The clinical trial is in planning phase and will be launched during 2015

Breast cancer researcher connected to Karma wins L’Oreal women’s science fellowship

Dr Li Jingmei, 31, received this year’s UNESCO-L’Oreal International For Women In Science Fellowship, one of 15 women scientists around the world to do so. Li Jingmei currently work as postdoctoral research fellow at the Agency for Science, Technology and Research’s Genome Institute of Singapore, but have strong connections to Karolinska Institutet and the Karma-group

She will receive her award at a ceremony in Paris this month.

With her US$40,000 award, Dr Li will spend two years at Karolinska Institutet in Sweden, where she previously completed her doctorate in medical science.


Dr Li Jingmei with mammogram images, which she studies to see how breast density predicts cancer risks. A young breast cancer researcher from Singapore will soon have the chance to continue her research on the data from the Karma cohort, thanks to a prestigious international science fellowship. — PHOTO:  L’OREAL SINGAPOR

Study shows mammographic density reduction as a prognostic marker of improved survival

Mammographic Density Reduction Is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients With Breast Cancer

Tamoxifen treatment is associated with a reduction in mammographic density and an improved
survival. However, the extent to which change in mammographic density during adjuvant
tamoxifen therapy can be used to measure response to treatment is unknown.

Overall, 974 postmenopausal patients with breast cancer who had both a baseline and a follow-up
mammogram were eligible for analysis. On the basis of treatment information abstracted from
medical records, 474 patients received tamoxifen treatment and 500 did not. Mammographic
density was measured by using an automated thresholding method and expressed as absolute
dense area. Change in mammographic density was calculated as percentage change from
baseline. Survival analysis was performed by using delayed-entry Cox proportional hazards
regression models, with death as a result of breast cancer as the end point. Analyses were
adjusted for a range of patient and tumor characteristics.

During a 15-year follow-up, 121 patients (12.4%) died from breast cancer. Women treated with
tamoxifen who experienced a relative density reduction of more than 20% between baseline and
first follow-up mammogram had a reduced risk of death as a result of breast cancer of 50% (hazard
ratio, 0.50; 95% CI, 0.27 to 0.93) compared with women with stable mammographic density. In
the no-tamoxifen group, there was no statistically significant association between mammographic
density change and survival. The survival advantage was not observed when absolute dense areas
at baseline or follow-up were evaluated separately.

A decrease in mammographic density after breast cancer diagnosis appears to serve as a
prognostic marker for improved long-term survival in patients receiving adjuvant tamoxifen, and
these data should be externally validated.

Jingmei Li, Keith Humphreys, Louise Eriksson, Gustaf Edgren, Kamila Czene, and Per Hall

Click here for full article in Journal of Clinical Oncology