|
 The BRCA1 and BRCA2 gene mutations put women at high risk for
breast, ovarian and other cancers, but mutations of other genes are
believed to confer extra risk as well.
Earlier this year, 17 genetic experts argued against testing for a
wider panel of breast cancer-related gene mutations until they are
proven to be valid and useful in clinical practice (see Reuters
story of May 27, 2015 here: http://reut.rs/1TvOoDf).
“There’s a lot of controversy even among experts,” said the senior
author of the new study, Dr. Leif W. Ellisen of Massachusetts
General Hospital Cancer Center in Boston.
For 15 years, at-risk women have only been tested for BRCA1 and 2,
but many companies now offer multi-gene panels for 20, 25 or 30
other genes, Ellisen told Reuters Health.
“Are patients better off getting these much broader tests?” he said.
“Does it actually change what you would tell them to do in terms of
screening, prevention, or risk management?”
According to the new results, at least for some women, it would
change their clinical management, he said.
Several of the authors of the new paper disclosed that they receive
research funding, consult for or are employed by genetic testing
companies like Myriad Genetics and Invitae Corporation.
Between 2001 and 2014, the study team did panel tests for 25 or 29
genes on 1,046 women who were referred for hereditary breast or
ovarian cancer gene testing, but had tested negative for BRCA
mutations. Most of the women had a personal history of breast or
ovarian cancer already.
The researchers found that 40 women, or 4 percent of the total
group, did have potentially harmful mutations in other genes. Of
those 40 women, 26 had mutations carrying low to moderate risk of
breast or ovarian cancer, eight had mutations associated with Lynch
syndrome, which increases colon and ovarian cancer risk, and three
had high-risk breast cancer genes.
Including another 23 patients who were referred into the study at a
late stage, there were 63 women positive for non-BRCA mutations. Of
those, the researchers decided that 33 would have been considered
for additional screening or prevention measures based on their
results. And for many, family testing would be recommended for
first-degree relatives, according to the report in JAMA Oncology.
Even among all appropriate candidates who are sent for genetic
testing, only nine percent will test positive for the BRCA
mutations, so an additional four percent who have non-BRCA mutations
is a significant number, Ellisen said.
[to top of second column] |
Often these additional women do not have a high risk of breast or
ovarian cancer, but some do have a high risk of colon or uterine
cancer, and would be referred for additional screening, he said.
Multigene testing is not more expensive than testing for the BRCA
mutations alone, he said.
Though these results indicate that additional genetic screening is
clinically useful, some genetic test results will be uncertain, and
it can be psychologically difficult for patients to deal with this
uncertainty, Ellisen said.
“We do not advocate for broad population-based screening,” he said.
“The interpretation of these tests is not a simple color-by-numbers
thing.” The vast majority of uncertain genes will be benign, but a
misinterpretation could lead a patient to a drastic, unnecessary
surgical procedure, he said.
“Many cancer genetics experts have again urged caution,
characterizing the use of multigene testing in the clinical setting
as premature,” Dr. Elizabeth M. Swisher of the University of
Washington Medical Center in Seattle writes in a commentary
accompanying the new paper.
“Yet thousands of women and their physicians are ignoring this
advice, ordering a wide selection of multiplex tests daily,” Swisher
writes. “The train has left the station and is unlikely to return,”
so it is important to assess how useful this additional testing can
be, she concludes.
SOURCE: http://bit.ly/1L98e2E and http://bit.ly/1L98pLj JAMA
Oncology, online August 13, 2015.
[© 2015 Thomson Reuters. All rights
reserved.] Copyright 2015 Reuters. All rights reserved. This material may not be published,
broadcast, rewritten or redistributed. |
