Even though they had no family history that would make them eligible for genetic testing, about 1 in 40 postmenopausal women diagnosed with breast cancer before age 65 had a mutation linked to cancer in the BRCA1 or BRCA2 gene, a rate similar to Ashkenazi Jewish women, according to an analysis of data from the Women’s Health Initiative.
This finding suggests that genetic testing may be beneficial for postmenopausal women who are newly diagnosed with breast cancer even if they don’t have risk factors for inheriting a mutation linked to breast cancer.
The research was published on March 10, 2020, by the journal JAMA. Read the abstract of “Prevalence of Pathogenic Variants in Cancer Susceptibility Genes Among Women With Postmenopausal Breast Cancer.”
Genetic mutations linked to breast cancer
A germline variant is a change, or mutation, in a gene that is inherited from your parents and is in all your DNA. “Pathogenic” means the mutation is linked to a higher risk of disease — in this case, breast cancer.
Two of the most well-known genes that can mutate and raise the risk of breast and/or ovarian cancer are BRCA1 and BRCA2. Women who inherit a mutation in either of these genes — from their mothers or their fathers — have a much higher-than-average risk of developing breast cancer and/or ovarian cancer.
Men with these mutations also have an increased risk of breast cancer, especially if the BRCA2 gene is affected, and possibly of prostate cancer.
About 5% to 10% of breast cancers are thought to be hereditary, meaning the cancer is linked to germline mutations passed from parent to child.
You are much more likely to have a genetic mutation linked to breast cancer if:
- You have blood relatives (grandmothers, mother, sisters, aunts) on either your mother's or father's side of the family who had breast cancer diagnosed before age 50.
- There is both breast and ovarian cancer on the same side of the family or in a single individual.
- You have a relative(s) with triple-negative breast cancer.
- There are other cancers in your family in addition to breast, such as prostate, melanoma, pancreatic, stomach, uterine, thyroid, colon, and/or sarcoma.
- Women in your family have had cancer in both breasts.
- You are of Ashkenazi Jewish (Eastern European) heritage.
- You are Black and have been diagnosed with breast cancer at age 35 or younger.
- A man in your family has had breast cancer.
- There is a known breast cancer gene mutation in your family.
Genetic testing guidelines
A number of expert groups have developed guidelines for breast cancer genetic testing. In 2019, The American Society of Breast Surgeons (ASBS) issued updated guidelines saying genetic testing should be made available to everyone who has been diagnosed with breast cancer. The ASBS updated guidelines followed research published in December 2018 showing that the National Comprehensive Cancer Network (NCCN) breast cancer genetic testing guidelines miss about half of people with a genetic mutation linked to breast cancer.
In February 2020, the NCCN announced updated breast cancer genetic testing guidelines that recommend genetic testing for people diagnosed with breast cancer if they:
- were diagnosed at age 45 or younger
- were diagnosed at age 46–50 and have unknown or limited family history, or have been diagnosed with a second breast cancer, or have one or more close relatives diagnosed with breast, ovarian, pancreatic, or prostate cancer
- were diagnosed with triple-negative breast cancer at age 60 or younger
- are of Ashkenazi Jewish ancestry
- have one or more close relatives diagnosed with breast cancer at age 50 or younger or ovarian, pancreatic, or prostate cancer at any age
- have two or more relatives diagnosed with breast or prostate cancer at any age
- have been diagnosed with breast cancer that has a genetic mutation found by genomic tumor testing that could increase cancer risk if the mutation is a germline mutation
Still, the initial NCCN genetic testing guidelines for people diagnosed with breast cancer were first developed about 20 years ago when testing was limited to two genes: BRCA1 and BRCA2. Genetic testing at that time also was very expensive, costing approximately $5,000 per test.
Since that time, genetic testing technology has advanced rapidly, allowing multiple genes to be tested at the same time. The cost of genetic testing also dropped dramatically — today, some genetic testing can be done for as little as $250.
How this study was done
To do this analysis, Stanford University researchers looked at information from 4,517 women who were part of the very large Women’s Health Initiative (WHI) trial that includes information from more than 161,608 postmenopausal women who were ages 50 to 79 when they joined the trial between 1993 and 1998. The WHI wants to find any links between health, diet, and lifestyle factors and health problems such as cancer.
None of the women in this analysis had been diagnosed with breast cancer when they joined the WHI. Of the women included in this analysis:
- 2,195 were diagnosed with breast cancer during the WHI
- 2,322 had not been diagnosed with breast cancer as of Sept. 20, 2017
Of the women who were diagnosed with breast cancer:
- half were older than 73 when they were diagnosed and half were younger
- 66.3% were white
Of the women who were not diagnosed with breast cancer:
- half were older than 81 at the last follow-up visit and half were younger
- 84.9% were white
The researchers did genetic testing on all the women using a Myriad Genetics test that looked for mutations in a panel of 28 genes, including BRCA1, BRCA2, ATM, BARD1, CDH1, CHEK2, NBN, PALB2, STK11, and TP53, which are considered to be linked to a higher risk of breast cancer.
Any genetic mutations found were classified as:
- pathogenic (harmful)
- likely pathogenic (probably harmful)
- uncertain significance (not enough is known about these mutations to know if they are harmful or not)
- benign (not harmful)
- likely benign (probably not harmful)
Overall, harmful mutations were found in 241 women:
- 148 who had been diagnosed with breast cancer
- 93 who had not been diagnosed with breast cancer
A harmful mutation was found in a gene associated with breast cancer in:
- 3.55% of women who had been diagnosed with breast cancer
- 1.29% of women who had not been diagnosed with breast cancer
This difference was statistically significant, which means that it was likely due to the difference in breast cancer diagnoses rather than just because of chance.
When looking specifically at harmful mutations in the BRCA1 or BRCA2 genes:
- 2.21% of women diagnosed with breast cancer when they were younger than 65 had a BRCA1 or BRCA2 mutation
- 1.09% of women diagnosed with breast cancer when they were age 65 or older had a BRCA1 or BRCA2 mutation
Of women who had a harmful mutation in the BRCA1 or BRCA2 genes:
- 30.8% of women diagnosed with breast cancer met NCCN genetic testing guidelines
- 20% of women not diagnosed with breast cancer met NCCN genetic testing guidelines
Of women who had a harmful mutation in another breast cancer-associated gene:
- 34% of women diagnosed with breast cancer met NCCN genetic testing guidelines
- 16% of women who had not been diagnosed with breast cancer met NCCN genetic testing guidelines
The researchers said this is the first study to suggest that postmenopausal women newly diagnosed with breast cancer who don’t have any risk factors for inheriting a mutation linked to breast cancer may benefit from genetic testing.
"There's been a lot of controversy in the field as to whether every woman with breast cancer should receive genetic testing," said Allison Kurian, M.D., associate professor of medicine and of epidemiology and population health at Stanford and lead author of the study, "in part because we didn't know how prevalent cancer-associated mutations are in this largest subgroup of newly diagnosed people — that is, women who develop breast cancer after menopause without the presence of any known hereditary risk factors.
"Now we know that the prevalence of cancer-associated BRCA1 and BRCA2 mutations in women diagnosed with breast cancer after menopause rivals that in women of Ashkenazi Jewish descent — a population that is currently encouraged to discuss genetic testing with their doctors," she continued. "We finally have a read on the likely benefit of testing this most common subgroup of breast cancer patients."
What this means for you
Research suggests that many people with mutations linked to breast cancer are not having genetic testing because they don’t meet NCCN testing guidelines. This means that people who don’t know they have a genetic mutation may not be told about all their options for reducing their risk of recurrence (the cancer coming back) or a new cancer.
If you’ve been diagnosed with breast cancer, you may want to talk to your doctor or a genetic counselor about your diagnosis and your family history and ask if having a multigene panel test makes sense for you. A genetic counselor or your doctor can help you understand the test and accurately interpret the results.
For more information on genetic testing, including types of genetic tests and how results are reported, visit the Breastcancer.org Genetic Testing pages.
For more information on genes and genetic mutations linked to breast cancer, as well as all the risk-lowering steps you can take if you have a genetic mutation, visit the Breast Cancer Risk Factors: Genetics page in the Breastcancer.org Lower Your Risk section.
If you've tested positive for a mutation linked to breast cancer and would like to talk about this with others who have also tested positive, join the forum Positive Genetic Test Results.
Written by: Jamie DePolo, senior editor
Reviewed by: Brian Wojciechowski, M.D., medical adviser
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