BRCA1 and BRCA2 in Breast Cancer

by Jason Wasserman MD PhD FRCPC
March 19, 2026

BRCA1 and BRCA2 are genes that normally protect cells from becoming cancerous. Their job is to repair damaged DNA and keep cell division under control. When one of these genes carries a harmful mutation — a change that prevents the gene from working properly — that protective function is lost, and the risk of developing breast cancer, ovarian cancer, and several other cancers rises substantially. Testing for BRCA1 and BRCA2 mutations is one of the most consequential tests in breast cancer care: a positive result has implications not only for the patient’s own treatment choices but potentially for the cancer risk of their biological relatives. It can also open doors to specific targeted therapies — drugs called PARP inhibitors — that work particularly well in cancers that have lost BRCA function.

What the test looks for

Every person is born with two copies of each gene — one inherited from each parent. BRCA1 and BRCA2 are tumour suppressor genes: their normal role is to detect and repair DNA breaks. When one copy of BRCA1 or BRCA2 is mutated and the second copy is subsequently lost or damaged in a cell, that cell loses its ability to repair DNA properly. It becomes far more likely to acquire additional mutations that lead to cancer.

BRCA1 and BRCA2 mutations come in two fundamentally different forms, and distinguishing between them is critical:

Germline mutations (hereditary). A germline mutation is one that was present in the egg or sperm cell at conception and is therefore carried in every cell of the body from birth. A person with a germline BRCA1 or BRCA2 mutation inherited it from one of their parents and has a 50% chance of passing it to each of their own children. Germline mutations are the basis of hereditary breast and ovarian cancer (HBOC) syndrome. They are identified through a blood or saliva test, not a tumour biopsy.
Somatic mutations (acquired). A somatic mutation is one that arose during a person’s lifetime, only within the cancer cells themselves. It was not inherited and cannot be passed to children. Somatic BRCA1 or BRCA2 mutations are identified through testing of the tumour tissue. They are relevant for treatment — particularly PARP inhibitor eligibility — but they do not carry the same hereditary implications as germline mutations.

Understanding which type of mutation is present — or whether both are — shapes what the result means for the patient and for their family.

Why is the test done

To assess hereditary cancer risk. A confirmed germline BRCA1 or BRCA2 mutation substantially elevates the lifetime risk of breast cancer (approximately 50–70% for BRCA1 and 45–70% for BRCA2, depending on the specific mutation and family history), as well as the risk of a second primary breast cancer, ovarian cancer, and in BRCA2 carriers, several other cancers including pancreatic and prostate cancer. This information changes long-term surveillance strategies and may influence decisions about risk-reducing surgery.
To guide surgical decisions at the time of breast cancer diagnosis. Patients with a germline BRCA mutation may choose more extensive surgery — such as bilateral mastectomy — to reduce the risk of a new cancer in the opposite breast, or salpingo-oophorectomy (removal of the fallopian tubes and ovaries) to reduce ovarian cancer risk. These are deeply personal decisions made in consultation with the surgical and genetic teams.
To determine eligibility for PARP inhibitor therapy. PARP inhibitors — including olaparib (Lynparza) and talazoparib (Talzenna) — are drugs that exploit a cancer’s inability to repair DNA when BRCA function is lost. They are approved for patients with germline BRCA1 or BRCA2 mutations and HER2-negative metastatic breast cancer, and for high-risk early-stage breast cancer following chemotherapy. Knowing the BRCA mutation status is necessary before these drugs can be considered.
To enable cascade testing of family members. If a germline BRCA mutation is identified in a patient, their first-degree relatives (parents, siblings, children) have a 50% chance of carrying the same mutation. Knowing the specific mutation in the family allows relatives to undergo targeted genetic testing and, if positive, to begin appropriate surveillance or risk-reduction measures — potentially preventing future cancers.
To inform platinum chemotherapy decisions. BRCA-mutated breast cancers — particularly triple-negative breast cancers with BRCA1 mutations — have shown enhanced sensitivity to platinum-based chemotherapy drugs such as carboplatin and cisplatin in some clinical settings. BRCA status may therefore influence chemotherapy selection in certain patients.

Who should be tested

Guidelines have expanded significantly in recent years regarding who should be offered BRCA1/2 testing. Historically, testing was limited to patients with strong family histories of breast or ovarian cancer. Current guidelines from major oncology organisations now support offering germline BRCA1/2 testing broadly to patients with:

Any newly diagnosed breast cancer — many guidelines now recommend offering germline testing to all patients with breast cancer, regardless of age or family history, given the direct treatment implications.
Triple-negative breast cancer diagnosed at any age.
Breast cancer diagnosed at age 50 or younger.
Bilateral breast cancer.
A personal or family history of ovarian cancer, pancreatic cancer, or prostate cancer (Gleason grade group 2 or higher), in addition to breast cancer.
Breast cancer in a man (male breast cancer has a strong association with BRCA2).
Ashkenazi Jewish ancestry (three founder mutations in BRCA1 and BRCA2 are substantially more common in this population).
A known BRCA mutation in a first-degree relative.

If you have not been offered genetic testing and believe you may meet one or more of these criteria, ask your oncologist or surgeon for a referral to a genetic counsellor.

How the test is performed

Germline testing

Germline BRCA1/2 testing is performed on a blood or saliva sample — not on tumour tissue. DNA extracted from blood cells (which carry the patient’s inherited genetic code) is sequenced to identify mutations in the BRCA1 and BRCA2 genes. This testing is arranged through a genetic counsellor or oncologist and is typically covered by provincial or private health insurance when clinical criteria are met. Results generally take two to four weeks.

Germline testing may use targeted sequencing of BRCA1 and BRCA2 alone, or it may be performed as part of a broader multi-gene panel that simultaneously tests dozens of cancer-related genes (including PALB2, CHEK2, ATM, and others). Multi-gene panels increase the likelihood of identifying a hereditary explanation but also increase the likelihood of identifying variants of uncertain significance (discussed below).

Somatic (tumour) testing

Somatic BRCA testing is performed on the tumour tissue — either the biopsy sample or the surgical specimen. It uses next-generation sequencing (NGS) to identify mutations in cancer cells. This type of testing is typically ordered by the oncologist when germline results are unavailable, when there is a specific need to assess somatic BRCA status for treatment planning (particularly PARP inhibitor eligibility in metastatic disease), or as part of comprehensive tumour molecular profiling.

Importantly, a somatic BRCA mutation identified through tumour testing does not confirm the presence of a germline mutation — but it can serve as a flag. When a somatic BRCA mutation is found on tumour testing, germline testing is typically recommended to determine whether it was inherited.

How results are reported

BRCA1/2 test results are reported in one of five categories, using the American College of Medical Genetics classification system:

Pathogenic variant (Class 5). A mutation that is clearly harmful — meaning it is known to disrupt the function of the BRCA1 or BRCA2 protein and significantly increases cancer risk. This is what is commonly referred to as “testing positive” for a BRCA mutation. Action is required: referral to a genetic counsellor, discussion of surveillance and risk-reduction options, and notification that family members may wish to be tested.
Likely pathogenic variant (Class 4). A mutation that is almost certainly harmful based on the available evidence, though not yet confirmed beyond doubt. Clinically managed the same as a pathogenic variant in most cases.
Variant of uncertain significance (VUS) (Class 3). A change in the gene sequence whose effect on protein function is not yet known. A VUS is neither a positive nor a negative result — it cannot be used to make clinical decisions in either direction. VUS results are common with multi-gene panel testing. Laboratories reclassify VUS results as evidence accumulates, and patients should not take preventive action based solely on a VUS.
Likely benign variant (Class 2). A variant that is almost certainly not harmful. No action required.
Benign variant (Class 1) / No pathogenic variant detected. No harmful mutation was found in the genes tested. This is a negative result. It substantially reduces — but does not eliminate — hereditary cancer risk, because not all hereditary breast cancer risk genes have been identified. A negative result in someone with a strong family history should still prompt discussion with a genetic counsellor.

What each result means

Pathogenic or likely pathogenic germline BRCA1 mutation. BRCA1 mutations are most strongly associated with triple-negative breast cancer and with a high lifetime risk of ovarian cancer (approximately 40–45%). Patients with a germline BRCA1 mutation who develop breast cancer may be offered bilateral mastectomy and risk-reducing salpingo-oophorectomy as options, typically recommended between ages 35 and 40. They are eligible for PARP inhibitor therapy if they have HER2-negative disease meeting the approved criteria. Family members should be offered testing.
Pathogenic or likely pathogenic germline BRCA2 mutation. BRCA2 mutations are associated with a broader range of cancer types, including breast, ovarian, pancreatic, prostate, and melanoma. Breast cancers in BRCA2 carriers are more often hormone receptor-positive than those in BRCA1 carriers. Ovarian cancer risk is lower than with BRCA1 (approximately 10–20%) but still substantially elevated above the general population. PARP inhibitor eligibility and surgical options apply as with BRCA1. Family members should be offered testing.
Somatic BRCA1 or BRCA2 mutation (tumour only). The mutation is present in the cancer cells but was not inherited. It does not increase the patient’s risk of other cancers, and it cannot be passed to family members. However, it may still predict sensitivity to PARP inhibitors — clinical trials and some approval pathways include somatic BRCA mutations. Germline testing should be performed to confirm the mutation is truly somatic.
Variant of uncertain significance (VUS). No action should be taken based solely on a VUS. The result does not confirm a hereditary risk and should not be used to guide surgical decisions. The laboratory will notify the ordering clinician if the variant is reclassified in the future. Genetic counselling is strongly recommended to help understand and cope with an uncertain result.
No pathogenic variant detected (negative). No BRCA1 or BRCA2 mutation was found. If testing was limited to BRCA1 and BRCA2 only, other hereditary cancer genes were not assessed and could still be relevant — particularly if the family history is strong. A negative BRCA result does not mean there is no hereditary risk; it means BRCA1 and BRCA2 are not the explanation. Multi-gene panel testing or referral to a genetic counsellor may be warranted depending on the clinical picture.

The role of genetic counselling

Genetic counselling is strongly recommended before and after BRCA testing — not because the test is technically complex, but because the results carry implications that extend well beyond the patient’s own cancer diagnosis. A genetic counsellor can:

Help assess personal and family history to determine which genes are most relevant to test.
Explain, in plain language, what a positive, negative, or uncertain result means before the test is done, so the patient is prepared.
Discuss the emotional and familial dimensions of a positive result — including the decision of whether and how to share results with relatives.
Coordinate cascade testing for family members once a mutation is identified.
Review results and updated interpretations when a VUS is reclassified over time.

In Canada, referrals to hereditary cancer programs and genetic counsellors are available through most cancer centres. Genetic counselling is covered by provincial health insurance for patients who meet referral criteria.

BRCA testing and other cancers

Although this article focuses on breast cancer, it is worth noting that a germline BRCA mutation identified in the context of breast cancer has implications for the risk of other cancers in the same patient:

Ovarian cancer: Risk-reducing bilateral salpingo-oophorectomy is generally recommended for BRCA1 carriers between ages 35–40 and for BRCA2 carriers between ages 40–45, or after completion of childbearing.
Pancreatic cancer: Surveillance protocols exist for BRCA2 (and to a lesser extent BRCA1) carriers with additional risk factors such as a family history of pancreatic cancer.
Prostate cancer: BRCA2 carriers have an elevated risk of aggressive prostate cancer and may benefit from earlier or more intensive prostate cancer surveillance.

These implications will be discussed with you by your oncologist and genetic counsellor as part of a comprehensive risk management plan.

What happens next

If a pathogenic germline BRCA mutation is found, you will be referred to (or should request) a genetic counsellor if you have not already seen one. A comprehensive risk management plan will be developed covering surveillance, risk-reducing surgery options, and family notification. Your oncologist will also review whether PARP inhibitor therapy is appropriate for your breast cancer treatment.
If a somatic BRCA mutation is found on tumour testing, germline testing will typically be recommended to determine whether the mutation was inherited. Your oncologist will assess whether you are eligible for a PARP inhibitor.
If a VUS is found, no clinical action is required based on the VUS alone. Genetic counselling is recommended. The laboratory will provide updated interpretations if the classification changes.
If the result is negative, no BRCA-specific risk management is required, though other hereditary risk genes may be worth testing depending on your personal and family history.
If you have not yet been tested and believe you may be eligible, speak with your oncologist or surgeon about a referral to a genetic counsellor or hereditary cancer program.

Questions to ask your doctor

Should I have germline BRCA1/2 testing based on my diagnosis, age, or family history?
Will my tumour also be tested for somatic BRCA mutations?
If I test positive for a BRCA mutation, what are my options for reducing the risk of cancer in my other breast or my ovaries?
Does a BRCA mutation make me eligible for PARP inhibitor therapy such as olaparib or talazoparib?
Should my family members be tested, and how do I arrange that?
If I received a variant of uncertain significance, what does that mean, and how will I find out if its classification changes?
If my BRCA test was negative, could I still have a hereditary form of breast cancer caused by a different gene?
Can you refer me to a genetic counsellor?