For women at high risk of ovarian and breast cancer, the
benefits of salpingo-oopherectomy — the prophylactic
removal of the ovaries and fallopian tubes — are
great enough to justify the surgery. The US Society of
Gynecologic Oncologists has supported the practice in
women who carry either of the two identified breast cancer
genes, BRCA1 and BRCA2.
But new research presented at the
annual conference of the American Society of Clinical
Oncology this month suggests that benefit is not evenly
distributed between these two groups of patients. In
the largest study of risk-reducing salpingo-oopherectomy
to date, a team led by Dr Noah Kauff, a gynecologist
and geneticist at Memorial Sloan-Kettering Cancer Center,
New York, found significantly greater breast cancer
risk reduction in women with the BRCA2 mutation.
BETTER
SAFE THAN SORRY
If there were such a disease as cancer of the appendix,
and it killed thousands of people every year, most of
your patients would want the useless organ removed.
That same logic has increasingly been applied to the
ovaries and fallopian tubes of high-risk women who are
willing to forego the ability to bear children.
These women have a high lifetime
risk of ovarian cancer and roughly a two-thirds probability
of developing breast cancer. Three studies have shown
that removing the ovaries and fallopian tubes can cut
the risk of subsequent ovarian, fallopian tube and primary
peritoneal cancer by 71"96%. It can also cut the risk
of subsequent breast cancer by 50-68%, at least if done
premenopausally.
Dr Kauff's study participants included
565 BRCA1 mutation carriers and 321 women with BRCA2.
Of these, 561 opted for risk-reducing salpingo-oopherectomy,
and 325 for ovarian surveillance.
Both groups benefited from prophylactic
surgery. Risk of ovarian cancer and peritoneal cancer
was all but eliminated, though a few early cases were
detected during the surgery. But the radical procedure
reduced the risk of breast cancer by much more in the
women with BRCA2 mutations. Indeed, breast cancer risk
was reduced by 72% in the BRCA2 group, but only 39%
in the BRCA1 cohort.
Dr Kauff said his team has a working
hypothesis to explain this. "Breast cancer in women
with the BRCA2 mutation is more likely to be estrogen
receptor-positive. In an explanatory analysis, which
has yet to be confirmed, it appeared the primary benefit
of oopherectomy was in protecting against ER-positive
cancer. And 65-80% of BRCA2 breast cancer is ER-positive,
compared to 10-25% of BRCA1 breast cancer."
TAILORED
TREATMENT
Dr Kauff said the findings will allow physicians to
tailor risk-reduction strategies to a given patient,
depending on the mutation she has inherited.
"We think about 7-10% of all breast
cancers are caused by genetic mutations, about half
of which are BRCA1 or BRCA2. So these mutations account
for 4-5% of all breast cancers and about 10% of ovarian
cancers," he said.
Of course, a residual number of
inherited breast cancers aren't linked to BRCA1 or BRCA2.
Dr Kauff said there's little doubt that a BRCA3 gene,
at the least, is still lurking undetected. That might
explain previous research in which families with extensive
breast cancer history but no recognized BRCA genes were
offered salpingo-oopherectomy. They too saw a reduction
in breast cancer risk " but not in ovarian cancer risk.
"The BRCA3 gene seems not to be linked to ovarian cancer
risk," he explained.
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