Joanne Kotsopoulos, PhD, Women’s College Research Institute, Toronto, Ontario, Canada reviews risks of various hormonal exposures among BRCA1/2 carriers, a topic she presented on at the 2022 San Antonio Breast Cancer Symposium.

Dr Kotsopolous discussed the potential protective effect of chemoprevention, the use of oral contraceptives and hormone replacement therapy, and the importance of oophorectomies. She stressed that these patients are a complex population requiring an individual, personalized approach.

Transcript

My name is Joanne Kotsopoulos. I'm a scientist at Women's College Hospital in Toronto, Ontario, Canada, and a professor at the University of Toronto. I'm excited to be here at the San Antonio Breast Cancer Symposium where I participated in the educational session on hereditary cancer. I was invited to talk about the role of hormonal exposures on cancer risk in women who have a pathogenic variant or likely pathogenic variant in the BRCA1 or BRCA2 gene. I'll refer to them as mutation carriers to keep it simple. I try to summarize the evidence of what we've learned over the last little while based on observational data and a lot of the work that our team has been focused on, trying to understand how exogenous hormones impact cancer risk.

I reviewed some of the more up-to-date evidence or tried to give a more comprehensive view of the role of various factors. I focused on the impact of tamoxifen chemoprevention and then also the use of exogenous hormones, specifically oral contraceptives and hormone replacement therapy in this population, and as well as some more recent data on the important role of bilateral salpingo-oophorectomy, or surgical removal of the ovaries, to help not only in preventing ovarian and fallopian tube cancer, but also its important role in all-cause mortality and significantly reducing deaths in this high-risk population. I think the main take home messages is that these individuals are a complex population. We're balancing multiple risks, breast and ovarian cancer risks, and other potential cancer risk. But the focus was breast and ovarian cancer.

Some of our recent data is suggestive of a potential protective role of tamoxifen use, but tamoxifen use has historically been low and remains low in our population. Whether we're going to be able to pinpoint an actual protective effect of this chemopreventive agent may be difficult given the low uptake. I also discussed some of the emerging role of another pathway, in particular the progesterone or RANK-signaling pathway as a potential target for these women. I think there's a lot of important basic science work that's been done for a couple decades now, and the fact that some of our observational work is in line or complementing some of this data pointing towards other targets for chemoprevention that might be more relevant for this population. Then I overview some of the existing evidence on oral contraceptive use. Again, we see a significant protective effect against ovarian cancer, but a potential increased risk for breast cancer. This is similar to what we see in the general population.

It shows that the important role of some of these exposures and how they have differing effects depending on what cancer you're thinking about. When we're managing these young women who are before the age of surgical prevention or may not even know they have a mutation yet, these are some of the important questions they're going to ask. Will oral contraceptives further increase my risk? We know that the lifetime risk in carriers is high. I think it's a personalized approach to managing these women because an additional increased risk due to oral contraceptive use for a few years may be okay for some women but may not be acceptable for others. Finally, our study on hormone replacement therapy after oophorectomy is showing a stronger potential increased risk with combination therapy, estrogen, and progestin-containing hormone replacement therapy. Again, in line with what we see in the general population.

There’s an important role for hormone replacement therapy in these women because most will have their ovaries removed at a young age and are forced into early surgical menopause. We need to avoid some of these other comorbidities and allow them to have an enhanced quality of life, especially when it's allowed. I think the main take-home message is managing risks in this population is hard. We know there's an important role of certain factors.

MRI screening is important, which one of the speakers spoke about. We don't have effective chemoprevention or definitive chemoprevention yet. We know that uptake is low. I'm not sure what the role is going to be for existing chemoprevention agents. Exogenous hormone use, there might be a small risk, but that may be acceptable for some. This is when the clinician-patient conversations are important. Each woman will opt for different options. There is an important role for hormone replacement therapy, and we must try to manage these women, not only using HRT, but also managing some of these adverse outcomes following oophorectomy such as bone health, cardiac health, and overall health.

Source:

Kotsopoulos J. “Hormonal exposure and risk in BRCA1/2 carriers.” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas.