Clinical Trial

Breast Cancer Research and Treatment

, Volume 120, Issue 1, pp 119-126

First online:

Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature

  • Youlia M. KirovaAffiliated withDepartment of Radiation Oncology, Institut Curie Email author 
  • , Alexia SavignoniAffiliated withDepartment of Biostatistics, Institut Curie
  • , Brigitte Sigal-ZafraniAffiliated withDepartment of Pathology, Institut Curie
  • , Anne de La RochefordiereAffiliated withDepartment of Radiation Oncology, Institut Curie
  • , Rémy J. SalmonAffiliated withDepartment of Surgery, Institut Curie
  • , Pascale ThisAffiliated withDepartment of Oncology Genetics, Institut Curie
  • , Bernard AsselainAffiliated withDepartment of Biostatistics, Institut Curie
  • , Dominique Stoppa-LyonnetAffiliated withDepartment of Oncology Genetics, Institut CurieUniversity Paris Descartes
  • , Alain FourquetAffiliated withDepartment of Radiation Oncology, Institut Curie

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Abstract

As tumours in BRCA1/2 mutation carriers might be more sensitive to radiation, we investigated after long-term follow-up whether mutation status influenced the rate of ipsilateral and contralateral breast cancers after breast-conserving treatment (BCT). BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer who had undergone BCT and radiotherapy. Patients were matched to 261 controls with sporadic breast cancer according to age at diagnosis and year of treatment. Controls were followed up for at least as long as the interval between diagnosis and genetic screening in familial cases. Rates of ipsilateral and contralateral cancer between groups were compared by the log-rank test. The BRCA1/2 mutations occurred in 20.6% of tested patients. Tumours in mutation carriers were more likely to be grade III (P < 10−4) and oestrogen receptor negative (P = 0.005) than in non-carriers and controls. Overall median follow-up was 161 months. There was no significant difference in ipsilateral tumours between mutation carriers, non-carriers and controls (P = 0.13). On multivariate analysis, age was the most significant predictor for ipsilateral recurrence (P < 10−3). The rate of contralateral cancer was significantly higher in familial cases: 40.7% (mutation carriers), 20% (non-carriers), and 11% (controls) (P < 10−4). After 13.4 years of follow-up, the rate of ipsilateral tumours was no higher in mutation carriers than in non-carriers or controls. As tumours in BRCA1/2 mutation carriers might be more sensitive to radiation, BCT is a possible treatment option.

Keywords

BRCA1/2 mutations Breast-conserving treatment Radiotherapy Recurrence