How do you approach the discussion about the potential risks of radiation therapy exposure and the development of secondary malignancies for patients with germline BRCA1/2 mutations?

It appears that the risk of secondary malignancies due to radiation exposure does not seem significantly enhanced in gBRCA-m carriers, unlike patients with Li-Fraumeni syndrome (for whom we would attempt to avoid radiation). The data on mBRCA-associated breast cancers would suggest that radiation is more effective for local-regional control than in non-BRCA-associated BC. However, I would not advocate for breast-conserving surgery with radiation as an alternative to mastectomies unless the patient insisted and was willing to accept the risks of new breast cancers with enhanced screening.

Generally, I agree with Drs. @Dr. First Last and @Dr. First Last that the decision to apply any preventive therapy involves weighing the risks and benefits of that therapy. We offer adjuvant radiation after breast cancer surgery to decrease the risk of local recurrence. It is recommended when the benefit of decreasing the risk of local recurrence outweighs the risks of developing other cancers, which include another breast cancer, lung cancer, esophageal cancer, and sarcoma. It is notable that secondary cancers are rare, and the rate is also influenced by other risk factors, including smoking and age at radiation.

So, the answer to the posed question is not necessarily simple. BRCA1/2 mutation carriers, especially BRCA1, tend to develop brea...

I believe that the benefit of breast and regional nodal irradiation in terms of reducing the risk of local or regional recurrence typically outweighs the risk of secondary breast or soft tissue malignancies, though I might favor omitting this treatment in a patient with likely marginal benefit from radiation - such as administration of postmastectomy chest wall and regional nodal irradiation in a patient with minimal nodal involvement.

In short, the value of RT in the adjuvant setting (in terms of local control and preventing recurrence) outweighs the negative effects from RT-induced malignancy.

Secondly, it helps to know the BRCA status before primary therapy, so it can be used in shared decision-making, which is an important point here. It is hard to recommend anything intelligently when patients have not been tested before you begin therapy (you are assuming they are negative in the majority of cases).

We adopted the AsBrS guidelines in 2019 and counsel and universally recommend germline testing to 100% of patients with BC who walk through our door. Having said that, we have prospectively tested 96% of all BC patients since then, which gives us a real rate of pathogeni...