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Familial Breast Cancer

Clinical Response to Induction Chemotherapy or Radiotherapy Related to BRCA1/2 Mutations Status

Fourquet, Alain, MD*; Stoppa-Lyonnet, Dominique, MD; Kirova, Youlia M., MD*‡; Sigal-Zafrani, Brigitte, MD; Asselain, Bernard, MD§ for the Institut Curie Breast Cancer Study Group Institut Curie Breast Ovary Cancer Risk Study Group

American Journal of Clinical Oncology: April 2009 - Volume 32 - Issue 2 - p 127-131
doi: 10.1097/COC.0b013e31817f9e1c
Original Article: Breast

Purpose: BRCA1/2 germline mutations are associated with impaired DNA double-strand break repair. We tested whether breast cancers in BRCA1/2 mutation carriers were more responsive to induction treatments than in noncarriers.

Patients and Methods: The BRCA1 and BRCA2 genes were screened for germline mutation in a retrospective cohort of 90 patients (with 93 tumors) with a family history of breast and/or ovarian cancer, treated with induction anthracycline-containing chemotherapy and/or radiotherapy. Median tumor size was 40 mm. Clinical responses and breast preservation rates were correlated to BRCA1/2 mutation status, and to other clinical and pathologic factors.

Results: A complete clinical response was achieved in 15/39 (46%) BRCA1/2-mutated tumors and in 7/54 (17%) nonmutated tumors (P = 0.008). Complete or major clinical response rate was observed in 55 of the 74 tumors treated with induction chemotherapy (74.3%). The overall complete or major clinical response rate in the tumors treated with induction radiotherapy was 68% (13/19 tumors). Following induction treatment by either chemotherapy or radiotherapy, more breast-conserving treatments could be performed in mutation carriers than in noncarriers: the rates of breast preservation were 82% in BRCA1/2-mutated tumors and 63% in nonmutated tumors, respectively (P = 0.045). BRCA1 mutation was the sole predictor of breast conservation.

Conclusion: Breast conservation after induction treatment was higher in BRmut+ tumors, and clinical response was related to aggressive tumor features correlated with BRCA1/2 mutations. This suggests that impaired repair mechanisms related to the BRCA1/2 mutations increased the chemosensitivity and radiosensitivity of large breast cancers. Further studies will need to determine the long-term outcome in these patients.

From the *Departments of Radiation Oncology, †Genetic Oncology, ‡Pathology, and §Biostatistics, Institut Curie, Paris, France.

Reprints: Dr. Alain Fourquet, MD, Department of Radiation Oncology, Institut Curie, 26 rue d'Ulm, F75248 Paris, France. E-mail:

© 2009 Lippincott Williams & Wilkins, Inc.