In an interview with _Pharmacy Times®,_ Matteo Lambertini MD, PhD, professor at University of Genova in Italy, shared that risk-reducing mastectomy and salpingo-oophorectomy were associated with significantly improved overall survival, disease-free survival, and breast cancer prevention in young BRCA carriers diagnosed with breast cancer. The data reinforce existing guidelines on risk-reducing surgeries for BRCA carriers and suggest young BRCA carriers with breast cancer should consider early risk-reducing mastectomy as part of their treatment plan. Lambertini noted that future research should focus on providing guidance for women with gene alterations other than BRCA.
**Pharmacy Times**
What is the association between risk-reducing surgeries (RRSS) and survival in young BRCA carriers with breast cancer?
**Matteo Lambertini MD, PhD**
Here the San Antonio Breast Cancer Symposium 2024, we have presented a large international study including young BRCA carriers with diagnosis of breast cancer at a young age, so age 40 or less. In this specific analysis, in this large data set, we have investigated the association between a risk reducing surgeries and survival. So, in other words, to look if undergoing a risk reducing mastectomy and/or risk reducing salpingo-oophorectomy was associated with an improvement in disease outcomes. The main result from this study is that we have shown indeed, that both risk reducing mastectomy as well as risk reducing salpingo-oophorectomy, are associated with a significant improvement in overall survival, but also in disease free survival and breast cancer.
**Pharmacy Times**
How do the findings of this study inform the decision-making process for young BRCA carriers considering RRSS as a preventive measure against breast cancer?
**Lambertini**
We have clear guidelines on how to manage cancer risk management strategies in BRCA carriers. The way the data that we have presented are going to help into this counseling is for the special and specific cohort of young women with breast cancer. So those patients that have been diagnosed with breast cancer at a young age and are also carrying a germline pathogenic variant in the BRCA genes. The guidelines are saying that risk reducing salpingo-oophorectomy is recommended between the age of 35 to 40 years for BRCA1 carriers, and from 40 to 45 years for BRCA2 carriers. Our data are reinforcing this concept in the cohort of patient including our study. The data that are probably a bit more novel is the risk reducing mastectomy data, because the guidelines are saying that this is a procedure to be considered, but there is no clear guidance on the age at the time of this procedure. Again, for the special clinical setting that we are targeting in these studies, of young women with diagnosis of breast cancer at a young age — if BRCA carriers, I will consider a risk reducing mastectomy earlier on in their treatment, because this has been associated with a significant improvement in outcomes in this special cohort of patient.
**Pharmacy Times**
What are the potential limitations and future research directions in understanding the long-term impact of RRSS on survival and quality of life in young BRCA carriers?
**Lambertini**
The main limitation of this study, that despite being a large international network, it is still a retrospective study with its potential biases because of the nature of the study. But also, the specific analysis on the risk-reducing surgeries in this setting has been quite complicated. It is a complex analysis with some risk of biases. However, we have tried to counteract the risk of these biases. We have done different models and different adjustment for trying to reduce as much as we could, the potential biases in this sort of analysis. The fact that all the different models provided the same results, so very consistent results is reassuring that these data are indeed data that we can trust, but still coming from a retrospective study. In terms of future direction, I think that what we must do is to provide information to those women with alteration in genes other than BRCA, because it's not only BRCA1 or BRCA2 that, when alternated, will increase the risk of breast cancer for this patient. We still need to provide more clear guidance on different topics, including risk-reducing surgeries.