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Current guidelines do not recommend genetic counseling and testing for most women over age 65 because they’re assumed to have a small chance of having a pathogenic variant in one of the high-penetrance genes (also known as high-risk genes)—BRCA1, BRCA2, and PALB2.
Widely used guidelines developed by the National Comprehensive Cancer Network (NCCN) also don’t recommend hereditary cancer testing (genetic testing) or yearly breast cancer screening MRIs for women older than age 65. One of the reasons is because few studies have specifically looked at predisposition genes in women over age 65 – either those who have been diagnosed with breast cancer, or those who haven’t.
For women older than 65, better estimates of the remaining lifetime risk of breast cancer linked with having a pathogenic variant in a predisposition gene are needed. (See blue box below for an overview of basic terms about inheriting cancer risks.) Knowing more about breast cancer risk can help a woman and her doctors make informed decisions about:
The United States-based Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium conducted the largest study to date of women in the United States diagnosed with breast cancer after age 65.
Several American Cancer Society (ACS) epidemiologists participated in the study, including Lauren R. Teras, PhD, Alpa V. Patel, PhD, and James M. Hodge, MPH. Some of the many other contributors included ACS grantee Julie Palmer, PhD, and former ACS grantees Jeffrey N. Weitzel, MD, and Fergus Couch, PhD, who was the study’s senior author.
It was previously believed that women diagnosed with breast cancer after age 65 were unlikely to have been born with any high-risk breast cancer mutations. This study shows that some women older than 65, such as those diagnosed with triple-negative breast cancer, are still likely to have genetic mutations and should be offered genetic counseling and testing.”
Lauren Teras, PhD
Senior Scientific Director, Epidemiology Research
Population Science, American Cancer Society
They reviewed data from about 27,000 women over age 65, with about half having a diagnosis of breast cancer. Data came from epidemiologic studies that included the ACS Cancer Prevention Studies, CPS-II and CPS-3.
The consortium published their findings from this study, showing that:
For women older than 65, this study provided evidence on:
Who should be considered for genetic counseling and testing. The authors state that this study provides evidence that women older than 65 should be considered for genetic counseling and testing when they have an ER- breast cancer (including TNBC) to help guide their care.
Who doesn’t need genetic counseling and testing. The authors confirm that women older than age 65 who don’t have a family history or an ER- subtype of cancer would not benefit from genetic counseling and testing because they have a low likelihood of having a pathogenic variant in a high-penetrance gene, such as BRCA1 or BRCA2.
Who might benefit from enhanced breast cancer screening. Based on their findings, the authors also support enhanced breast cancer screening (such as MRI) for women over age 65 who have BRCA1 or BRCA2 mutations and possibly also those with CHEK2 and PALB2 mutations, whether or not they’ve been diagnosed with breast cancer. If a woman has been diagnosed with breast cancer, MRI screening could be used to look for second cancers or recurrence.
Family members with the same pathogenic variants may also benefit from enhanced breast cancer screening. These women and their family members may also want to talk with their doctors about the pros and cons of preventive surgery to remove their breasts and/or ovaries to prevent future cancers in those areas.
The knowledge gained about the prevalence of pathogenic variants in breast cancer predisposition genes can be used to inform appropriate care, including guidelines for genetic counseling and testing as well as guidelines for breast cancer screening and other risk-management strategies for:
Permanent changes in the DNA sequence of a gene are called gene mutations. Some scientists think that “gene variant” is a more accurate term because changes in DNA do not always lead to disease. Sometimes they’re used as synonyms.
Genetic variants can have a large or small effect on the likelihood of developing a particular disease. The term “pathogenic” refers to something that causes a disease. When genetic variants lead to disease, they’re called pathogenic variants, or pathogenic mutations.
Genes that are vulnerable to cancer-causing variants or changes are called cancer-predisposition genes. In some cases, a cancer-predisposition gene is inherited, or passed along from generation to generation. Several dozen cancer-predisposition genes have been identified, and about 5 to 10% of all cancers result directly from those that are inherited from a parent.
For example, BRCA1 and BRCA2 are inherited cancer predisposition genes. Mutations on these genes increase the risk for developing certain cancers.
The term penetrance is used to describe how many people carrying a mutation or cancer predisposition gene will eventually develop cancer. If everyone who inherits a mutation develops cancer, that mutation is said to have complete penetrance. If some people don’t, it’s incomplete or reduced penetrance. If most people with an inherited mutation develop cancer, that mutation has high penetrance. For example, pathogenic variations on the BRCA1 and BRCA2 genes are high-penetrance gene mutations. Other gene mutations are in categories considered to be moderate- or low-penetrance.