PHOENIXA matched case-control study from Yale University suggests that early-stage breast cancer patients with deleterious BRCA1 or 2 mutations are at greater risk of late recurrences after breast-conserving surgery and radiation therapy than those without a mutation. Further, many of these late recurrences appear to be new primary breast cancers.
Every single recurrence had either a different histology from the primary or was in a different location in the breast, Bruce C. Turner, MD, PhD, now at Thomas Jefferson University and the Kimmel Cancer Center, said at the annual meeting of the American Society of Therapeutic Radiology and Oncology (ASTRO). This suggests that all these tumors were not recurrences but were de novo.
The study included 52 women from the Yale University database who had experienced a local breast tumor recurrence following lumpectomy and radiation therapy and who had agreed to donate blood for DNA testing and undergo a detailed family history.
BRCA1 and 2 sequencing showed that 8 (15%) of these 52 patients, all unselected for age and family history, had a deleterious gene mutation, and these patients presented with late tumor recurrences. Their mean time to recurrence was 8.7 years, compared with 5.5 years for patients with no BRCA1 or 2 mutations.
Interestingly, Dr. Turner said, we found that 2 of the 8 patients with a BRCA1 or 2 mutation had absolutely no family history of breast or ovarian cancer, suggesting that perhaps a family history of breast/ovarian cancer is not always adequate to identify those patients at risk of having these mutations.
The researchers then matched the 15 patients from the study who were under age 40 at presentation with 15 controls under age 40 at presentation who had not experienced a local relapse.
Among the 15 index cases, 6 (40%) had a clear deleterious BRCA1 or 2 mutation, Dr. Turner said, while only 1 (7%) of the 15 controls had such a mutation. Seven percent is about what one would expect to find in a group that is selected for age but unselected for family history or Ashkenazi ancestry, he said.
Dr. Turner concluded that genetic analysis to identify BRCA1 or 2 mutations may identify breast cancer patients at increased risk for breast tumor relapse or de novo breast tumor formation following lumpectomy and radiation therapy. Clearly, further larger studies are now warranted.