Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy
Introduction
Breast conservative surgery and radiation therapy is a standard treatment for early stage breast cancer. Numerous randomised trials have proven the equivalence in survival between breast-conserving surgery with radiotherapy and mastectomy in early stage breast cancer 1, 2, 3, 4, 5, 6, 7, 8.
BRCA1 and BRCA2 mutations are found in approximately 5% of all breast cancers, and in up to 20–25% in the case of a family history of breast and/or ovarian cancer [9]. It has been shown previously that BRCA1 mutation carriers develop tumours with higher grade and proliferation index, and lower oestrogen receptor levels than those who do not have a mutation 10, 11. On the other hand, BRCA2 mutation carriers present tumours with pathological features similar to sporadic cases 10, 11, 12, 13, 14, 15, 16. It has also been shown that BRCA1 mutation carriers tend to have a worse outcome [13].
BRCA1 and BRCA2 proteins are involved in DNA repair in response to ionising radiation, through various mechanisms that are not yet fully understood, such as DNA double-strand break repair, apoptosis and cell cycle checkpoint control 17, 18. The safety of breast conservation with radiotherapy in BRCA mutation carriers is controversial, because of the potential of ionising radiation to induce new primaries in the treated breast.
The issue of breast cancer recurrence after breast-conserving treatment in BRCA1 and BRCA2 mutation carriers was addressed in a small number of studies, using different methodologies to compare breast cancer outcome in carriers and in patients with sporadic cancers, with several biases related to the retrospective nature of these studies 19, 20, 21, 22, 23, 24, 25. A matched cohorts study was conducted at the Institut Curie to assess the rate of recurrences and contralateral breast cancers in BRCA1/2 mutation carriers compared with sporadic control cases.
Section snippets
Patients
A cohort of women with small breast cancers treated at the Institut Curie with breast-conserving surgery and radiotherapy from 1981 to 2000, were analysed retrospectively. These patients were invited to attend the family cancer clinic of the institute between 1990 and 2001 if they presented a familial history of breast or ovarian cancer. Selection criteria and the procedure used for molecular testing, as well as the method of obtaining information such as family cancers, age at cancer diagnosis
Results
Nineteen patients had a BRCA1 mutation, and 8 had a BRCA2 mutation. This represents 20.6% of all patients with a family history (21.3% tumours). Patients’ characteristics are presented in Table 1. As shown in this table, the familial and sporadic cohorts were well-matched with regard to age at diagnosis. All cases were treated the same year as their controls, using the same treatment modalities. The follow-up of controls was at least equal to the time-interval between diagnosis and genetic
Discussion
This retrospective case-control study showed that at a 9-year median follow-up, the rate of breast cancer recurrence was not higher in BRCA1 and BRCA2 mutation carriers than in non-carriers with family history, or sporadic cases, despite more aggressive features associated with BRCA1 mutations.
These results are in accordance with the findings of a multi-institute case-control study of Pierce and colleagues [24], where patients in the genetic cohort were matched by age and date of diagnosis with
Conflict of interest statement
None declared.
Acknowledgement
This paper was presented at the 4th European Breast Cancer Conference, 16th–20th March 2004, in Hamburg.
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