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
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.
In a substudy to Karma, scientists will study why it is more common among women with high mammographic density to develop breast cancer. The study will investigate breast tissue biopsies from women with low breast density and compare this with biopsies from women with dense breasts.
Karma Normal is a collaboration between researchers at the Karolinska Institute and physicians at the mammography clinic in Helsingborg Hospital. The study will invite randomly selected women in the Helsingborg area who already participates in Karma.
Medical doctors take biopsies from healthy breasts using the same procedures as in investigating a breast lump. The biopsies are analyzed with different methods which will present a picture of what the tissue looks like. The researchers will look into any cell composition that represents density and any composition that represents changes that would lead to a cancer later on in life.
The aim is to understand what gives rise to the density and what cell types and genes are influencing development of cancer, and hopefully to prevent breast cancer in the future.