| U-M
study shows no differences in side effect rates, and suggests
similar recurrence rates
originally posted October 26, 2000
ANN ARBOR, MI - Women with breast cancer
who carry a genetic mutation that heightens their risk of
the disease might not have to fear having radiation therapy
as previously thought, according to a new study led by University
of Michigan Comprehensive Cancer Center researchers.
In fact, the results suggest, women with mutations
of the BRCA 1 or 2 gene who
had breast-conserving surgery after cancer diagnosis may get
the same benefit from radiation therapy with no greater incidence
of short- or long-term side effects as women with non-hereditary
cancer. Some doctors have been concerned that in carriers
of the BRCA 1 or 2 mutation, radiation's ability to damage
DNA in normal breast tissue might outweigh its benefit in
killing cancer cells.
U-M
radiation oncologist Lori Pierce, M.D., the study's leader,
will report on Oct. 24 at the annual meeting of the American
Society for Therapeutic Radiation Oncology in Boston.
Pierce and her colleagues from the U-M Comprehensive Cancer
Center and several partner institutions published results
of the same study in the October issue of the Journal
of Clinical Oncology.
"With five years of followup data in hand, we
see no increased incidence of skin fibrosis, pain, shortness
of breath or other side effects, which suggest that DNA repair
mechanisms are intact in BRCA 1 and 2 mutation carriers,"
says Pierce. "The fear of harm, based on laboratory findings
that the BRCA gene product is linked to the cells' own repair
system, may have unnecessarily prevented some women from getting
the full range of therapeutic care."
The retrospective study also found similar high
rates of survival, and low rates of cancer recurrence in the
affected breast, for 71 women with the BRCA 1 or 2 mutations
and 213 without a mutation who had similar diagnoses, surgical
procedures and treatments.
But, Pierce cautions, the cancer recurrence
data are based on only 5 years of follow-up. Data on how the
women fared after 10 years, due to be available as early as
spring of 2002, will be needed to say more certainly whether
radiation therapy can continue to reduce the risk of cancer
recurrence in the treated breast or the development of new
cancers in the same breast.
As many as 10 percent of all breast cancer cases
result from inherited factors, while the rest are thought
to be sporadic, or non-hereditary. In recent years, scientists
have pinned down two genes - dubbed BRCA 1 and BRCA 2 - that
seem to account for most of the inherited cases.
Women who inherit a BRCA 1 or 2 mutation are
known to have an increased risk - as high as 55 to 60 percent
by age 70 - of developing breast or ovarian cancer, probably
because they have no genetic "safety net." In other words,
they have no extra normal copy to take over if their one normal
copy in a single breast cell undergoes mutation and the cell
produces an abnormal form of the protein encoded by the gene.
Even though scientists don't yet understand
the exact workings of the proteins that BRCA 1 and 2 produce,
they think they may be tied to the mechanisms cells use to
repair damaged DNA. Hence, the controversy over treating these
women with radiation.
Since radiation therapy can reduce a woman's
chance of breast cancer recurrence from 35 to 40 percent to
10 percent after lumpectomy, the question is an important
one. But physicians have worried that therapeutic radiation,
no matter how carefully planned and delivered, could cause
DNA damage in the remaining normal copy of BRCA 1 or 2 or
that carriers of either mutation would show evidence of increased
sensitivity to radiation following radiation treatment.
Pierce and her colleagues set out to test these
hypotheses by studying the outcome of American and Canadian
women with either a BRCA 1 or 2 mutation who underwent radiation
following lumpectomy for early stage breast cancer.
The researchers compared those women's outcomes
and complication rates with the same endpoints in closely
matched women with non-hereditary forms of the disease. About
half the women in each group had had chemotherapy as well
as surgery and radiation.
Since the study was looking for differences
in the incidence of any effects of radiation, not just cancer-causing
effects, the researchers looked at the women's records to
see how many side effects, or complications, they had experienced
after their radiation treatments.
The results showed no differences in the low
rates of short-term side effects between the BRCA mutation
carriers and sporadic cancer patients. Both groups had similar
incidence of skin redness and irritation, and a 1 to 2 percent
rate of dry cough or shortness of breath and breast discomfort.
No significant differences were observed either in the rates
of long-term complications such as skin fibrosis, chronic
shortness of breath or rib fractures.
Turning to cancer recurrence, the researchers
found no significant differences in the rates at which cancer
returned to the affected breast after five years of follow-up
compared to the sporadic patients. For those whose cancer
did come back in the same breast, additional treatment such
as mastectomy kept it in check. As for the other breast, mutation
carriers had a higher rate of cancer, as expected.
Finally, the researchers looked at survival
after five years. Again, no difference turned up between the
two groups in relapse-free survival, cause-specific survival,
and overall survival.
Says Pierce, "While it's too soon to say that
breast-conserving therapy results in long-term rates of cancer
control in the treated breast in BRCA 1 or 2 carriers, it
is clear that radiation is well-tolerated and can be safely
given to women who carry either breast cancer mutation. Clinically
indicated adjuvant radiotherapy shouldn't be omitted in carriers
based on toxicity concerns."
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