Translational Research Controversies
Friday, December 8 • 1:30 p.m. – 2:30 p.m. • Stars at Night Ballroom 3-4
Presentation: The KARISMA-2 Low Dose Tamoxifen Trial
Per Hall, MD, PhD
What is your presentation about?
I will talk about a randomized controlled trial, KARISMA-2, where we tested lower doses of tamoxifen than the clinically accepted 20 mg dose. The aim was to see if the therapeutic effect was retained at doses of 1, 2.5, 5 and 10 mg and at the same time, in detail, study side effects at different doses.
I will also briefly talk about the active metabolite of tamoxifen, endoxifen. What plasma levels of endoxifen are required to reach the therapeutic effect and what doses of tamoxifen do these endoxifen concentrations correspond to?
What makes this topic important in 2023?
Tamoxifen reduces recurrence of and mortality from breast cancer in women diagnosed with estrogen receptor positive breast cancer. Tamoxifen also reduces the incidence of breast cancer if provided to healthy women. Adherence to tamoxifen therapy is, however, low due to severe, menopausal-like side effects and low adherence negatively affects prognosis. Studies have shown that not even 50% of the patients pick up their prescriptions after a couple of years treatment.
To improve adherence to a very effective therapy is of utmost importance and it could be that lower doses is the way forward.
How did you get involved in this particular area of breast cancer research, care, or advocacy?
I am a medical oncologist by training. Working as a clinician I focused on breast cancer. Some 20 years ago I decided to devote my time to breast cancer epidemiology, mainly prevention, early detection and risk modelling. I have for long been thinking about how successful cardiologists have been in identifying risk factors for myocardial infarction and effectively treating hyperlipidemia and hypertension. As a result, over the last decades incidence and mortality from myocardial infarction have declined. At the same time, breast cancer incidence has dramatically increased. We therefore created the Karma Cohort including ≈ 70 000 women. We have detailed information about each woman, ranging from genotypes to mammograms. We have used the cohort to develop risk models, that is, to identify the individual risk of breast cancer. We have conducted several randomized controller prevention trials and we have tested alternative screening modalities, such as contrast enhanced mammography.