SAN ANTONIOBreast cancer patients with BRCA 1 or 2 mutations undergoing
breast-conserving surgery plus radiotherapy do not have more in-breast
recurrences or radiotherapy complications than their counterparts without the
germ-line mutation, and they derive particular benefits from prophylactic
bilateral oophorectomy, according to 10-year results from a large collaborative
database reported at the 26th San Antonio Breast Cancer Symposium (abstract 5).
"The functions of BRCA 1 and 2 are largely unknown, though we do know they
are important in maintaining genomic integrity. In vitro studies have shown
increased radiation sensitivity in cells deficient in BRCA 1 protein, and BRCA
2 has been shown to be a factor in DNA repair mechanisms," said Lori Pierce,
MD, of the University of Michigan, Ann Arbor. These characteristics could
conceivably alter treatment outcomes and possibly lead to chronic radiotherapy
complications due to alterations in DNA repair, she noted.
The study was based on chart reviews from 12 medical centers of 180 BRCA 1/2
carriers and 496 matched controls with sporadic breast cancer (no more than one
postmenopausal relative with breast cancer and no family history of ovarian
cancer). All patients were diagnosed with stage I-II disease and treated with
breast-conserving surgery plus radiotherapy. Age at diagnosis was 40.5 years in
the genetic cohort and 41.4 in the sporadic cohort. Median follow-up was 7.7
and 6.5 years, respectively.
Treatment was comparable between the two cohorts regarding surgery and
radiation dose and field. More patients in the genetic group received
chemotherapy and more in the sporadic group received tamoxifen. These factors
were adjusted for in the multivariate analysis.
Recurrence Rates Similar Overall
In the overall data set, mutation carriers did not have significantly higher
rates of local recurrence than persons with sporadic cancers, although there
was a trend of slightly worse recurrence rates in the breast and more cancer
occurrences outside of the breast among the carriers, Dr. Pierce reported.
Local-only recurrence as the first failure occurred in 22 of 180 genetic
patients (12%) and 38 of 496 sporadic patients (7.6%). Analysis of the
in-breast tumor recurrences by age, nodal status, and stage also revealed no
significant increases among the genetic cohort. Contralateral recurrences,
however, were significantly higher among carriers than sporadic patients (P
= .0001), she said.