The BRCA1 and BRCA2 genes produce proteins that help repair damaged DNA, acting as tumor suppressors that protect against cancer development. When a person inherits a pathogenic variant, or mutation, in one of these genes, the ability to repair DNA is compromised, significantly increasing the lifetime risk for breast, ovarian, and other cancers. The question of how a mother’s negative test result impacts her child’s risk profile is a common one that requires understanding the specific mechanics of genetic inheritance.
How BRCA Mutations Are Inherited
Inherited BRCA mutations follow an autosomal dominant pattern. This means a person only needs to inherit one copy of the altered gene from either parent to have the increased cancer risk. Everyone inherits two copies of the BRCA1 and BRCA2 genes, one from the mother and one from the father. If a parent carries a BRCA mutation, they have a 50% chance of passing that specific mutation to any of their children, regardless of the child’s sex.
The genes are located on non-sex chromosomes, meaning the father’s genetic contribution is just as significant as the mother’s. The risk of inheriting a BRCA mutation is a coin flip for every child of a carrier parent.
Interpreting a Maternal Negative Test Result
If a mother tests negative for a BRCA mutation, the interpretation of that result for her child depends heavily on the context of the test.
True Negative Result
The most informative result is a “true negative.” This occurs when the mother was tested specifically for a known pathogenic variant already identified in her family, such as in her own mother or sister. If she tests negative for that specific familial mutation, she did not inherit it and cannot pass it on. This effectively eliminates the risk to her child tied to that maternal lineage.
Uninformative Negative Result
A negative result is less definitive if the mother was the first person in the family tested, or if her test was a general panel that found no known high-risk variants. This is called an “uninformative negative.” While it indicates she does not carry the high-risk mutations included in the panel, significantly lowering her child’s risk, it does not rule out a different, rare, or undiscovered cancer-predisposing mutation not covered by the testing.
Variant of Uncertain Significance (VUS)
Genetic testing sometimes reveals a Variant of Uncertain Significance (VUS). This is a change in the gene sequence whose effect on cancer risk is not yet known. A VUS is not treated as a pathogenic mutation and does not typically change medical management. Regardless of the testing context, a maternal negative result offers significant reassurance regarding the maternal contribution to the family’s potential risk.
Genetic Risk Beyond the Maternal Line
A mother’s negative BRCA result addresses only half of the child’s genetic inheritance, as the father also contributes a copy of the BRCA genes. If the father carries a BRCA mutation, the child’s 50% inheritance risk remains, completely independent of the mother’s negative status. Since BRCA mutations increase the risk for male-associated cancers, such as prostate and male breast cancer, the father may be an unknowing carrier.
The mother’s negative test also does not account for inherited risk from other high-risk genes that are not BRCA1 or BRCA2. Modern genetic testing often includes genes associated with hereditary cancer syndromes, such as PALB2, CHEK2, and ATM. For instance, PALB2 works in partnership with BRCA2 and is recognized as the third most prevalent breast cancer gene.
If the family’s cancer pattern is not explained by the mother’s negative result, the inherited risk could stem from a mutation in one of these other genes. Mutations in genes like CHEK2 and ATM confer an elevated lifetime risk for breast cancer, though generally not as high as a BRCA mutation. A comprehensive assessment requires considering the entire family history, including the paternal side and other susceptibility genes.
Baseline Risk and Next Steps
Even with a confirmed true negative result for a familial BRCA mutation, every individual retains a general population risk, often referred to as “baseline risk.” For an average woman in the United States, the lifetime risk of developing breast cancer is approximately 13%. This baseline risk is due to a combination of aging, lifestyle, and non-inherited genetic factors.
The most important step following a maternal negative result is to discuss the full family history with a genetic counselor or specialist. This professional can evaluate all factors, including the paternal lineage and the presence of other cancers, to determine the most accurate risk profile. If the specific high-risk genetic factor has been ruled out, the focus shifts to standard cancer screening guidelines tailored to the individual’s overall risk level.