Adetunji T. Toriola, MD, PhD, professor of surgery at Washington University School of Medicine, explains how breast cancer prevention campaigns for premenopausal women have changed and how RANK ligand inhibition could influence screening accuracy.
Emphasizing the role of modifying lifestyle factors for premenopausal women can go a long way in reducing breast cancer risks, Adetunji T. Toriola, MD, PhD, professor of surgery at Washington University School of Medicine.
What are some current tactics being utilized to prevent breast cancer among premenopausal women?
At the population level, population-based modifiable risk factors, such as avoiding alcohol, limiting weight gain, being physically active, and also limiting the use of oral contraceptives have been known to be very effective. In women with estrogen receptor–negative breast cancer, breastfeeding has also been seen to be very effective in reducing the risk of AR [antigen receptor]–negative breast cancer. When it comes to chemoprevention medication, tamoxifen, which is a selective estrogen receptor modulator, has been shown to be very effective in reducing breast cancer within premenopausal women, but of course the attendant side effects limit widespread use in premenopausal women. For higher-risk women with BRCA mutations, there are additional options, such as bilateral salpingo-oophorectomy and other surgical procedures which are known to be very effective as well.
How have breast cancer prevention campaigns evolved over time and what more needs to be done to further improve breast cancer numbers?
I think there's a lot of awareness on breast cancer prevention, and that's been due to a lot of work that has been done over time. For instance, back in the early 2000s, there was this very strong risk associated with hormone replacement therapy use in postmenopausal women. Of course, when that was published, that led to a reduction in the use of hormone replacement therapy and a concomitant reduction in incidence of postmenopausal breast cancer. But ever since then, there has been a gradual annual increase in breast cancer incidence in both pre- and postmenopausal women. Like I said, some of the things we can do is keep on emphasizing the role of modifying lifestyle factors in reducing the risk over time.
What role does RANK ligand inhibition play in breast density and how does this influence the accuracy of breast cancer screenings?
That's a great question, and worked done by my lab has shown that women who have higher RANK ligand signaling gene expression within the breast tissues have increased breast density. We have also shown that having higher circulating soluble RANK ligand levels within the blood is associated with a higher risk of breast density among women who have higher progesterone levels. Based on those findings, we started a phase 1 clinical trial to see whether targeting RANK ligand and signaling in high risk women with dense breasts will lead to reduction in biomarkers and pathways that are associated with breast cancer. And that's what we found so far. Based on that, we then started a phase 2 clinical trial looking at RANK ligand inhibition in high-risk women with dense breasts. This is ongoing. This is funded by the NIH [National Institutes of Health]. It's ongoing. We are probably two-thirds close to completing the trial. So, I'm hoping that within the next 2 years, we'll have data on that to present to the public.