Preventive Radiotherapy to the Opposite Breast in BRCA Carriers: An Alternative to Surgery?

Hereditary Breast Cancer, BRCA Mutations and Preventive Approaches

Breast cancer is the most common malignancy among women worldwide, and most cases are sporadic. However, among every 10 breast cancers, approximately 1 (10%) develops because of inherited genetic mutations. Of these hereditary breast cancers, 50–60% are attributable to BRCA1 or BRCA2 gene mutations . In other words, approximately 5-6% of all breast cancers are BRCA1/2-related.

This proportion is even more striking in patients diagnosed at a younger age:

• In breast cancers diagnosed before age 40, the prevalence of BRCA1/2 mutations may reach 15-20%.
• The proportion is even higher in young patients with a family history, bilateral breast cancer or a diagnosis of triple-negative breast cancer.

BRCA genes play a key role in homologous recombination, the pathway that repairs cellular DNA damage. Mutations in these genes increase both the risk of developing breast and ovarian cancer at a young age and patients' susceptibility to developing a second primary cancer .

In women carrying a BRCA1/2 mutation, the lifetime risk of developing breast cancer can reach 70%, while the risk of a new cancer in the opposite (contralateral) breast can reach 25-30% within 10 years.

Because of this high risk, the approach to women with a BRCA mutation at diagnosis should consider both the existing tumor and the future of the opposite breast. Although bilateral mastectomy has traditionally been viewed as the most effective way to reduce these risks, many patients are not ready for this surgery. For patients who do not want this option for cosmetic, psychological or medical reasons, preventive (prophylactic) radiotherapy to the opposite breast is emerging as a less invasive alternative.

A study conducted in Israel by Dr. Elle Evron and colleagues, published on May 8, 2025 in JAMA Oncology , reports 10-year long-term results from a phase 2 trial and aims to shed light on this critical question:

"Can preventive radiotherapy to the opposite breast prevent or delay the development of a new breast cancer in women who carry a BRCA mutation?"

In this article, we examine the study findings in detail and also discuss adjuvant the scientific literature on whether radiotherapy is safe in BRCA carriers.

Long-Term Results Suggest Preventive Radiotherapy May Offer a New Alternative

The long-term follow-up results of this phase 2 study provide important data for evaluating the effectiveness of this strategy.

• The study was not randomized ; patients were assigned to the RT or observation arm according to their own preferences .
• The researchers studied patients who did not want bilateral mastectomy, targeting a group that did not agree to the maximum preventive strategy.
• For this patient group, comparing RT versus observation reflects a dilemma encountered in real-world practice.
• The effectiveness of RT to the opposite breast had never previously been evaluated with such long prospective follow-up.

Study Design

• Participants: 162 women carrying a pathogenic BRCA1/2 variant
• Mean age: 49.7 (range: 32–76)
• Treatment period: May 2007 – October 2017
• Groups:
  • Preventive radiotherapy group (80 patients)
  • Observation-only control group (82 patients)
• Primary endpoint: Rate of contralateral breast cancer within 10 years

Key Findings

🧬 Risk of Contralateral Breast Cancer

• Preventive RT group: 11 patients (13.8%)
• Control group: 15 patients (18.3%)
• Statistical significance: P = 0.24 (the difference was not significant, but the trend was noteworthy)

💡 However, a notable point was:
The time to development of contralateral breast cancer was 90 monthsin the preventive RT group and 40 months in the control group.
P < 0.001 → this difference was highly statistically significant.
This indicates that preventive RT substantially delayed the development of cancer.

🛑 Elective Mastectomy Rate

• Preventive RT group: 1 patient (1.3%)
• Control group: 9 patients (10.9%)
• P = 0.02 → a significant difference

🔄 Ipsilateral (Same-Breast) Tumor Recurrence

• Similar in both groups (6 patients, approximately 7.5%)
• Median time to recurrence was 81 months in the preventive RT group
• Time to recurrence showed a 41-month delayin favor of RT

Clinical Interpretation and Recommendations

• According to this study, preventive radiotherapymay substantially delay contralateral breast cancer, even if it does not prevent it.
• This may directly influence patients' quality of life and decision-making:
  • For patients who wish to avoid removal of both breasts, it may offer a middle ground.
  • Later development of cancer may also provide more time for follow-up and treatment strategies.
• Study limitations:
  • Not randomized (groups were determined by patient preference)
  • Relatively small number of patients
  • Larger randomized studies are needed

Expert Commentary

The researchers comment: "Although this approach is controversial, its potential to delay the onset of contralateral breast cancer is noteworthy. Larger, multicenter studies should clarify the effects of this strategy," emphasizing that the method warrants further investigation.

Conclusion:

Preventive radiotherapy is emerging as a possible alternative to bilateral mastectomy in BRCA carriers: a minimally invasive, potentially effective approach. It may be a promising option, particularly for patients with cosmetic concerns or those who decline surgery. However, multidisciplinary assessment with the patient and an individualized risk–benefit analysis are essential before a decision is made.