Women with so-called dense breasts, which are made up of a lot of glandular tissue and connective tissue but little fat, are at increased risk of developing breast cancer (see box). This is because breast cancer occurs in these very tissues.
“You don’t get cancer in the fat itself,” says Per Hall, professor at the Department of Medical Epidemiology and biostatistics at Karolinska institutet.
The drug tamoxifen has been shown in several large studies to be effective in preventing recurrence of breast cancer, for women affected by hormone-controlled cancer (see box). Tamoxifen blocks the effect of estrogen, which does not go unnoticed.
– Younger women are thrown directly into menopause and it’s not funny. Many people get side effects in the form of hot flashes, sweating, vaginal discharge, decreased sex drive and disturbed sleep, says Per Hall.
His group has in a previous study examined how women choose to take tamoxifen. They were then able to show that after five years of treatment, just under half of the women recovered the drug. This they published in 2015 in the Journal Journal of Clinical Oncology.
“It made us think about whether it could work with lower doses of tamoxifen, compared to the standard dose of 20 milligrams per day that is currently recommended,” says Per Hall.
To get a picture of tamoxifen’s effect, they chose to study breast density, as it is already known that an effect of tamoxifen is precisely that the breasts become less dense, which contributes to the reduced risk of cancer. The so-called Charisma study began in 2016.
Here, women without a history of breast cancer between the ages of 40 and 74 who were called for mammography were given tamoxifen in doses of 1, 2.5, 5, 10 and 20 milligrams as well as non-effective treatment, placebo.
Each group included 240 women and for the individual woman the study lasted six months. Before and after the treatment, the density of the breasts was measured using mammography. The results were striking.
– We could see that the density decreased equally with all the active doses, except at 1 milligram. It was bingo! We had thought that 10 milligrams would work, but that 2.5 was just as good was unexpected, says Per Hall.
He describes that the study has already received a lot of attention and the low dose of tamoxifen has been renamed ”baby Tamoxifen”.
The second outcome measure was the rate of side effects, which the women reported on a mobile app.
– Here we could see that all doses below 20 milligrams gave 50 percent less side effects. What we did not expect was that we only saw these effects in women who had not passed menopause, ” he says
Per Hall emphasizes that the new study, which is published in the Journal of Clinical Oncology, shows that tamoxifen’s effect on breast density was clear even at the low doses.
“We cannot conclude from these data that the protection against cancer recurrence is just as good, but we want to study this in a next step. And if the side effects are minor, the hope is that more women will have the strength to carry out the entire treatment, he says.
In dense breasts, with mammography, it is difficult to see early cancerous changes, as both tumors and the tissues are white.
“Finding tumors in non-dense breasts requires only good vision, as they shine like stars in the night sky, but in dense breasts it is difficult even for the most skilled radiologists to see what’s what,” says Per Hall.
Therefore, in collaboration with an American company, the development of an AI-based software is now underway that identifies changes in the mammography image that indicate an increased risk of breast cancer.
Individual risk assessment could catch more cancer cases
Per Hall is also interested in ways to more clearly prevent breast cancer in women at increased risk. About every fourth cancer occurs in the intermediate period between two mammography examinations, so-called interval cancer.
“We would like to see if individual risk assessment could capture more of these,” he says.
In a study published in Radiology last year, it was described how women with elevated individual risk were eight times higher risk of developing such interval cancer. Now planning is underway to conduct such a study.
Here, the idea is that women who are invited to mammography should be able to participate and then have their individual risk assessed – using parameters such as breast density, genetics, living habits, whether they have given birth and breastfed children, and so on.
Per Hall describes that women with a particularly low risk can sparse out their mammography examinations, while those with higher ones should be examined more frequently.