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