Abstract:

Background and purpose: BRCA1/2 plays an important role in maintaining the genome stability. Whether BRCA1/2 germline mutation could increase the tumor sensitivity to radiotherapy, thereby inducing secondary primary cancer after radiotherapy is unclear. This study aimed to investigate whether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer (TNBC) patients with BRCA1/2 germline mutation. Methods: This research was based on a previously reported retrospective cohort, i.e., the Fudan University Shanghai Cancer Center TNBC cohort. Between January 1, 2007 and December 31, 2014, a total of 292 female TNBC patients with BRCA1/2 mutation were enrolled. We performed logistic regression analysis in patients without BRCA1/2 germline mutation (n=261) and BRCA1/2 germline mutation patients (n=31), respectively, to assess the risk factors affecting the incidence of second primary cancer. We then performed interactive analysis on the above two analyses to evaluate the interactive effect between BRCA1/2 germline mutation and postoperative radiotherapy. P<0.05 indicates a statistically significant difference. The research was approved by Fudan University Shanghai Cancer Center TNBC Ethics Committee (050432-4-2108), and each patient provided written informed consent. Results: Logistic regression analysis in patients with BRCA1/2 germline mutations showed that postoperative radiotherapy significantly increased the risk of secondary primary disease compared to non-radiotherapy [odds ratio (OR)=2.475, 95% confidence interval (CI): 1.933-3.167, P<0.001]. In patients without BRCA1/2 germline mutation, the effect of radiotherapy on the incidence of second primary tumor was not significant. There was a significant interaction between BRCA1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer (OR=9.710, 95% CI: 0.320-295.250, P=0.193). Conclusion: Although statistical analysis results show that patients with BRCA1/2 germline mutations have an increased risk of developing a second primary tumor after postoperative radiotherapy compared to patients who have not received radiotherapy, there is no significant correlation between BRCA1/2 germline mutations and radiotherapy for the development of a second primary tumor. Therefore, patients with BRCA1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

Key words: Breast cancer, BRCA1, BRCA2, Radiotherapy, Second primary cancer