A drug used to stop milk production after childbirth could hide a completely different utility. International research has found that a dose of cabergoline administered at the end of lactation approximately halved the proportion of genetically predisposed mice that developed breast cancer. The finding is reinforced by retrospective data from women that point in the same direction, although the possible preventive effect will still need to be demonstrated through clinical trials.
The study, published in the scientific journal Cancer Discovery, of the American Association for Cancer Research, has Spanish participation from the Salamanca Cancer Research Center, a joint center of the University of Salamanca and the CSIC. Among the researchers who signed the work are Natalia García-Sancha, Roberto Corchado-Cobos, Christopher A. Maxwell and Jesús Pérez-Losada, as well as scientists from institutions in different countries. Maxwell is a professor at the Faculty of Medicine at the University of British Columbia (Canada) and a researcher at the BC Children's Hospital Research Institute.
Cabergoline is a dopamine agonist that decreases prolactin secretion and can be used to inhibit or suppress milk production when medically indicated. The research focused on a very specific moment in the mother's life: the period after weaning. Once lactation has ended, a good part of the structures that had developed to produce milk are no longer necessary and the mammary gland begins a remodeling process known as involution.
Christopher Maxwell uses a very graphic comparison to explain the phenomenon: "It's like a fruit tree." During pregnancy and lactation, the researcher explains, the breast develops the structures necessary to produce milk, while during involution a kind of "winter" occurs in which these structures restart. This physiological process of tissue removal and remodeling is precisely what researchers believe may be important in understanding postpartum cancer risk.
The team worked with mice that had alterations in Brca1 and Trp53, two essential genes for controlling cellular damage and whose alteration is related to the development of tumors. The scientists observed that, in these predisposed animals, the process of involution of the mammary gland could remain incomplete. By administering a single dose of cabergoline after ending breastfeeding, the drug enhanced this involution and delayed the appearance of tumors, in addition to reducing their incidence.
Tumor precursor cells decrease
Analysis of the animals' mammaries offers clues about what might be happening. Cabergoline reduced the mammary ductal area and the proliferation of epithelial cells, in addition to reducing the presence of certain tumor precursor cells. The researchers also observed modifications in the immune response, including a reversal of T cell exhaustion. Taken together, the changes point to a more complete remodeling of the gland after lactation.
The big question was whether any similar signal could be found in humans. To investigate, the team used medical data from women in Spain and Norway and analyzed cohorts that together included more than 150,000 women with information on cabergoline use. Some had received the drug on medical advice to suppress lactation after childbirth, after a pregnancy loss or in situations in which they could not breastfeed.
Combining the results, the researchers found that women under age 50 who had received cabergoline had an approximately 69% lower risk of developing postpartum breast cancer than those who had not taken the drug. This is, however, an association observed retrospectively: these data do not demonstrate that cabergoline is directly responsible for this reduction nor do they justify using the medication on its own to prevent a tumor.
