MRI may lower breast cancer deaths from variants in 3 genes

Date:
February 17, 2022
Source:
University of Washington School of Medicine/UW Medicine
Summary:
Annual MRI screenings starting at ages 30 to 35 may reduce
breast-cancer mortality by more than 50% among women who carry
certain genetic changes in three genes, according to a comparative
modeling analysis. The predictions involve pathogenic variants in
ATM, CHEK2 and PALB2 genes - - which collectively are as prevalent
as the much-reported BRCA1/2 gene mutations.



FULL STORY ========================================================================== Annual MRI screenings starting at ages 30 to 35 may reduce breast-cancer mortality by more than 50% among women who carry certain genetic changes
in three genes, according to a comparative modeling analysis to be
published Feb.

17, 2022, in JAMA Oncology.


==========================================================================
The predictions involve pathogenic variants in ATM, CHEK2 and PALB2 genes
- - which collectively are as prevalent as the much-reported BRCA1/2 gene mutations. Authors of the study, published in JAMA Oncology, contend that
their findings support MRI screening in some of these women earlier than existing preventive-care guidelines propose.

"Screening guidelines have been difficult to develop for these women
because there haven't been clinical trials to inform when to start
and how to screen," said Dr. Kathryn Lowry, an assistant professor of
radiology at the University of Washington School of Medicine. She was
the paper's lead author.

The work was a collaboration of the Cancer Intervention and Surveillance Modeling Network (CISNET), the Cancer Risk Estimates Related to
Susceptibility (CARRIERS) consortium, and the Breast Cancer Surveillance Consortium.

Using established breast-cancer simulation models, the researchers input
age- specific risk estimates provided by CARRIERS and recent published
data for screening performance. The CARRIERS data involved more than
32,000 breast- cancer patients and a similar number of patients who had
no cancer.

"For women with pathogenic variants in these genes, our modeling
analysis predicted a lifetime risk of developing breast cancer at 21%
to 40%, depending on the variant," Lowry said. "We project that starting
annual MRI screening at age 30 to 35, with annual mammography starting
at age 40, will reduce cancer mortality for these populations of women
by more than 50%." The simulations compared the combined performance
of mammography and MRI against mammography alone, and projected that
annual MRI conferred significant additional benefit to these populations.



==========================================================================
"We also found that starting mammograms earlier than age 40 did not have
a meaningful benefit but increased false-positive screens," Lowry added.

Results from CISNET models have informed past guidelines, including the
2009 and 2016 U.S. Preventive Services Task Force recommendations for
breast cancer screening in average-risk women.

"Modeling is a powerful tool to synthesize and extend clinical trial and national cohort data to estimate the benefits and harms of different
cancer control strategies at population levels," said Dr. Jeanne
Mandelblatt, a professor at Georgetown Lombardi Comprehensive Cancer
Center and a senior author on the paper.

The simulations in this study also predicted the volume of false-positive screening results and benign biopsies, per 1,000 women scanned, that
would accompany the authors' recommendations for annual MRIs starting
earlier. Those projections translate to about four false-positive
screening results and one to two benign biopsies per woman over a 40-year screening span, the authors said.

To realize a benefit of cancer screening guidelines based on genetic susceptibility, a woman would need to know she carries an implicated gene variant before receiving a disease diagnosis. More often it's the case
that a genetic test panel is administered after someone tests positive
for cancer - - too late to be of preventive value for the patient but potentially life- saving for blood relatives who could seek genetic
testing.



========================================================================== "People understand very well the value of testing for variants in BRCA1
and BRCA2, the most common breast cancer predisposition genes. These
results show that testing other genes, like ATM, CHEK2, and PALB2, can
also lead to improved outcomes," said Dr. Mark Robson. He is chief of
Breast Medicine Service at the Memorial Sloan Kettering Cancer Center
and a senior author on the paper.

The researchers hope their analysis will aid the National Comprehensive
Cancer Network (NCCN), the American Cancer Society and other organizations
that issue guidance for medical oncologists and radiologists.

"Overall what we're proposing is slightly earlier screening than what the current guidelines suggest for some women with these variants," said Dr.

Allison Kurian, a professor at the Stanford University School of Medicine
and senior author on the paper. "For example, current NCCN guidelines
recommend starting at age 30 for women with PALB2, and at 40 for ATM
and CHEK2. Our results suggest that starting MRI at age 30 to 35 appears beneficial for women with any of the three variants." Funding for this
study came from the Breast Cancer Research Foundation (17- 137); the
National Institutes of Health / National Cancer Institute (U01CA199218, U01CA253911, R35CA197289, P30CA014520, P30CQA0008748, P01CA154292,
U54CA163303, R01Hs018366-01A1); the American Cancer Society (RSG- 16-018-01-CPHPS); and the Patient-Centered Outcomes Research Institute
(PCS- 1504-303070).

========================================================================== Story Source: Materials provided by University_of_Washington_School_of_Medicine/UW_Medicine.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Kathryn P. Lowry, H. Amarens Geuzinge, Natasha K. Stout, Oguzhan
Alagoz,
John Hampton, Karla Kerlikowske, Harry J. de Koning, Diana L.

Miglioretti, Nicolien T. van Ravesteyn, Clyde Schechter, Brian L.

Sprague, Anna N. A. Tosteson, Amy Trentham-Dietz, Donald Weaver,
Martin J. Yaffe, Jennifer M. Yeh, Fergus J. Couch, Chunling
Hu, Peter Kraft, Eric C. Polley, Jeanne S. Mandelblatt, Allison
W. Kurian, Mark E. Robson, Steven N. Hart, Katherine L. Nathanson,
Susan M. Domchek, Christine B.

Ambrosone, Hoda Anton-Culver, Paul Auer, Elisa V. Bandera,
Leslie Berstein, Kimberly A. Bertrand, Elizabeth S. Burnside,
Brian D. Carter, Heather Eliassen, Mia Gaudet, Christopher Haiman,
James M. Hodge, David J. Hunter, Eric J. Jacobs, Esther M. John,
Charles Kooperberg, James V.

Lacey, Loic Le Marchand, Sara Lindstrom, Huiyan Ma, Elena Martinez,
Susan Neuhausen, Polly A. Newcomb, Katie M. O'Brien, Janet E. Olson,
Irene M.

Ong, Tuya Pal, Julie R. Palmer, Alpa V. Patel, Sonya Reid,
Lynn Rosenberg, Dale P. Sandler, Rulla Tamimi, Jack A. Taylor,
Lauren Teras, Celine M. Vachon, Clarice Weinberg, Siddhartha
Yadav, Song Yao, Argyrios Ziogas, Jeffrey N. Weitzel, David
E. Goldgar. Breast Cancer Screening Strategies for Women With ATM,
CHEK2, and PALB2 Pathogenic Variants. JAMA Oncology, 2022; DOI:
10.1001/jamaoncol.2021.6204 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220217122325.htm

--- up 10 weeks, 5 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)