In a brand-new thesis, Mattias Hammarström studied whether lower dosages of tamoxifen and likewise its active metabolite endoxifen for direct administration, as a preventive medication might minimize adverse effects while still impacting breast tissue in healthy females. The findings recommend that lower dosages of tamoxifen and a low dosage of endoxifen might use a much better balance in between biological results and negative effects, possibly adding to more individualised methods to breast cancer avoidance.
Picture: Gunilla Sonnebring
Breast cancer is the most typical cancer amongst females worldwide. Treatments have actually enhanced, avoiding breast cancer stays an essential objective. Some ladies might gain from preventive medication, however for healthy ladies, the possible advantages need to be stabilized versus adverse effects. Tamoxifen has actually been utilized to deal with breast cancer for years and can likewise minimize the danger of establishing the illness. Endoxifen is thought about among the most active metabolites of tamoxifen and has actually not yet been assessed as a brand-new drug for breast cancer avoidance. Tamoxifen and its metabolites obstruct the impacts of the hormonal agent estrogen in breast tissue and thus hinder estrogen-driven cancer development. Side results such as hot flashes and night sweats can dissuade females from taking preventive treatment.
Mattias Hammarström is job supervisor In the KARMA program and PhD trainee at the Department of Medical Epidemiology and Biostatistics Karolinska Institutet, and his thesis consists of 4 research studies, based upon 2 randomised, placebo-controlled scientific trials, the KARISMA trials, in healthy ladies dealt with for 6 months.
What have you carried out in your research studies?
“We investigated different doses of tamoxifen and endoxifen and examined side effects, treatment adherence and changes in mammographic breast density. We used breast density as a measure of treatment response. Some previous studies indicate a lower breast cancer risk if density declines during treatment, although it does not prove that a treatment prevents breast cancer.”
What are the most crucial lead to your thesis?
“Lower doses of tamoxifen were associated with less severe side effects, particularly among women who had not reached menopause. In these women, low levels of endoxifen in the blood were also associated with similar reductions in breast density, seen in the standard 20 mg dose of tamoxifen. My studies also showed that side effects can influence whether women continue taking preventive medication. We found that early worsening of symptoms such as hot flashes was associated with subsequent non-adherence of tamoxifen. When endoxifen was given directly, both 1 mg and 2 mg reduced breast density compared with placebo. Women receiving 1 mg reported a similar symptom profile to those receiving placebo, while 2 mg was associated with more hot flashes and night sweats. Together, the findings support further research into lower-dose tamoxifen and low-dose endoxifen as possible ways to achieve a better acceptance and uptake in primary breast cancer prevention in women with a high risk of breast cancer.”
Why did you end up being thinking about this subject?
“Our research group has been working for more than 15 years to reduce the burden of breast cancer through prevention. Initially, I worked as a clinical trial manager, coordinating the practical aspects of our studies, including staff, study protocols, monitoring and trial operations. Later, I had the the opportunity to become more involved in the scientific work through PhD studies. I share the vision of our entire research group: if we can prevent breast cancer before it develops, we can reduce both the suffering experienced by individuals and the costs to society. However, our goal should not be to offer preventive treatment to as many women as possible, but to identify those most likely to benefit, while carefully balancing the potential benefits and harms for each individual.”
What do you believe should be performed in future healthcare and research study?
“The most important next step is to investigate whether lower doses of tamoxifen and oral endoxifen can also reduce breast cancer incidence. Our studies used mammographic breast density as a biomarker of treatment response. Although reductions in breast density are associated with lower breast cancer risk, we cannot conclude that the reductions observed in our studies translate into fewer breast cancers. Therefore, larger studies with long-term follow-up are needed to establish their preventive effectiveness.”
Doctoral thesis
Mattias Hammarström, November 2026.
Realities about doctoral theses
A doctoral thesis is the last composed item of a postgraduate education, which in Sweden represents 4 years of full-time research studies. It differs in between various disciplines how a doctoral thesis is structured. In the field of medication, the doctoral trainee normally gathers 3 to 5 clinical posts and provides them together with a thesis summary or introduction, a so-called ‘kappa’ (actually indicating topcoat in Swedish).
After the doctoral trainee has actually passed the general public defence of the thesis, she or he gets a postgraduate degree (likewise called a PhD), which is the greatest possible instructional degree in Sweden. Karolinska Institutet has roughly 2,000 active doctoral trainees and each year around 350 doctoral theses are released at our university.
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