That adjuvant hormone therapy lowers the risk of breast cancer recurrence by approximately 40 per cent and breast cancer specific mortality with approximately 30 per cent has been shown in numerous studies. Proportion of women that stop taking their medication ranges from 20-70 per cent but few studies have addressed predictors of discontinuation of adjuvant hormone therapy.

In a study published in June 2015 (Wei He, Fang Fang, Catherine Varnum, Per Hall, Mikael Eriksson, Kamila Czene, Journal of Clinical Oncology) it was found that women at higher risk of discontinuation were more likely to have a family history of ovarian cancer, to be younger than 40 years or older than 65 years, and to use analgesics and hypnotics /sedatives. These results are most clinically relevant since doctors can use the results to identify factors that predict which patients will stop using adjuvant hormone therapy.

The research on discontinuation is continuing with a focus on breast cancer patients that after discontinuation later takes up therapy. To restart therapy is to the benefit of patients but the prognosis does not reach that of those patients that sticks to therapy. However, it is significantly better than for those who stops altogether. The paper is accepted for publication in Journal of the National Cancer Institute.

One of the focuses of Karma is to reduce the number of women diagnosed with breast cancer. There are several ways of decreasing the risk of breast cancer. Interventions range from increased physical activity to prophylactic mastectomy (surgically removing the breasts). The Karma Intervention Trial, Karisma, aims at identifying the optimal preventive dose of the anti-hormonal drug tamoxifen.

Tamoxifen is used by breast cancer patients to lower the risk of a breast cancer recurrence. It has been shown that perfectly healthy women lower their risk of breast cancer by 50% if they use tamoxifen. However, tamoxifen is not used for prevention due severe side effects.

It is not obvious that the same dose should be used for prevention as the dose given to breast cancer patients. We are therefore testing if lower doses of tamoxifen have the same therapeutic effect as clinically accepted 20 mg.

Using data from the Karma Cohort, Mikael Eriksson, Karolinska Institutet, has developed a risk prediction tool that identifies women at very high of developing an interval cancer. Interval cancers are breast cancers diagnosed in the interval between two scheduled mammography screens. Interval cancers are considered to particularly aggressive cancers but are quite heterogeneous in their clinical behavior.

A tool that identifies women at high risk of interval cancers has the potential to improve mammography screening programs through selection of women that are in need of additional examination and not just a mammogram.

A manuscript has been submitted to Breast Cancer Research.

On the 15^th of January, Dr Thang Thrinh, Karolinska Institutet, defended his thesis entitled ”Determinants of breast cancer risk; focusing on mammographic density”. Thang’s thesis deals with how physical activity, alcohol consumption and cigarette smoking affect the risk of breast cancer through their influence on mammographic density.

Mammographic density is defined as the radiographically dense tissue, consisting of glandular and connective tissues, appearing bright on a mammogram, whilst non-dense, fatty tissue appears dark on a mammogram. The more bright the mammogram, the more glandular cells and the higher the risk of developing breast cancer. See images below (left: non-dense breast, right: highly dense breast).

Women who participated in the Karma study answered a large number of questions related to lifestyle when they entered the study. Participants were invited to the study when they performed the biannual mammography screening. Dr Thang wanted to find out if women who, for example, drank more wine had more dense breasts than women who totally abstained from alcohol.

In short, the conclusions that could be drawn from this thesis was:

Women who were physically active had a lower mammographic density, which most certainly reduces the risk of breast cancer. The more vigorous the physical activity, the lower the breast density. We also wanted to find out if women with an increased risk of breast cancer needed to do harder physical exercise than women with a lower risk. Background risk of breast cancer was estimated using the Tyrer – Cuzick score. Our findings suggested that women with a higher background risk of breast cancer needs to be more physically active, to reduce breast density, than women with lesser background risk.

Regarding alcohol consumption the findings are quite the opposite. The more alcohol a woman drinks, the higher the breast density and the higher the risk of breast cancer. However, it seems that daily consumption of wine has to exceed 1 glass wine/day to influence breast density. Similar to the findings of physical activity, background risk of breast cancer influenced how alcohol affects mammographic density. If you have a high risk of breast cancer you should be careful with alcohol.

Finally dr Thang studied change in mammographic breast density among cigarette smoking women. Surprisingly enough, in women who smoke the density is lower than in non-smoking women, despite the fact that smoking is known to increase the risk of breast cancer. Thang explained the effect of cigarette smoking on breast density as tobacco having an ”anti-hormonal” effect (which lowers the density) but that tobacco contains so many other toxic / carcinogenic substances that increase the risk of breast cancer so the overall effect is an increased risk of breast cancer.

Professor Per Hall, dr Thang’s supervisor, comments on the results: ”The findings are exciting and show that in the future, when we are able to predict a woman’s individual risk of breast cancer, lifestyle related advise can be given in preventive breast cancer care. As a matter of fact, already today, we can advise women who wish to reduce their risk of breast cancer to be physically active, drink moderately and not to smoke.

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:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0104417

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: http://www.ncbi.nlm.nih.gov/pubmed/25012995

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.

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

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

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

[Press release, 27 March 2013] More than 80 genetic ’spelling mistakes’ that can increase the risk of breast, prostate and ovarian cancer have been found in a large, international research study within the framework of the EU Network COGS. For the first time, the researchers also have a relatively clear picture of the total number of genetic alterations that can be linked to these cancers. Ultimately the researchers hope to be able to calculate the individual risk of cancer, to better understand how these cancers develop and to be able to generate new treatments.

The main findings are published in five articles in a special issue on genetic risk factors for cancer in the prestigious scientific journal Nature Genetics. The articles originate from COGS (Collaborative Oncological Gene-environment Study), an EU-based consortium where more than 160 research groups from all over the world are included. In the five COGS studies 100,000 patients with breast, ovarian or prostate cancer and 100,000 healthy individuals from the general population were included.
http://www.nature.com/ng/journal/v45/n4/full/ng.2592.html?WT.ec_id=NG-201304