What Is an ATM Gene Mutation? What You Need to Know

I Am an ATM Carrier—What Happens Now? Current, Realistic Information on Risk, Screening and Treatment

The ATM gene helps direct the detection and repair of damaged DNA in cells. People who carry an inherited (congenital) change in one copy of this gene have an increased risk of certain cancers, particularly breast and pancreatic cancer. However, this increase is more limited than in BRCA1 and BRCA2 carriers: most women who carry an ATM variant do not develop breast cancer during their lifetime. We updated this article as of October 2026 using the American College of Medical Genetics and Genomics (ACMG) 2024 guideline on ATM management and the NCCN 2026 guideline. Hereditary cancer syndromes and their targeted treatments and the importance of DNA repair in cancer have been discussed previously.

Why Does This Matter?

Multigene hereditary cancer panels are increasingly used in cancer patients and their families. After BRCA1 and BRCA2, changes in the ATM gene are among the most frequently identified findings in these tests. Approximately one in every 100–200 people in the general population is estimated to be an ATM carrier. The result can often be unexpected and worrying; questions such as ‘Is it like BRCA?’, ‘Should I have my breasts removed?’ and ‘Will X-rays or radiotherapy harm me?’ are common.

Answers to these questions have become substantially clearer in recent years. Large international studies showed that ATM-related risk is lower than that associated with BRCA genes, and in 2024 an international management guideline specifically for ATM carriers was published for the first time. The aim is to establish surveillance that matches the actual risk without unnecessarily frightening carriers.

What Is an ATM Gene Mutation?

An ATM gene mutation is an inherited change that disrupts the function of the ATM gene, which detects DNA damage and initiates repair. People carrying a change in one copy of the gene are called ‘ATM carriers’ and have moderately increased risks of breast, pancreatic and prostate cancer. Changes in both copies cause the rare condition ataxia-telangiectasia.

What Does the ATM Gene Do?

The name ATM comes from the English initials of ‘ataxia telangiectasia mutated’. Located on chromosome 11, the gene produces an ‘alarm’ protein that detects severe damage in which both DNA strands break. This protein stops cell division, activates the repair system (homologous recombination) and causes the cell to destroy itself if the damage cannot be repaired. Disruption of this pathway can allow damaged cells to multiply and cancer to develop over time.

The Difference Between Carrier Status and Ataxia-Telangiectasia

Not Every ‘ATM Result’ Means the Same Thing

• Pathogenic or likely pathogenic variant: A change known to disrupt the gene's function. The risk and screening recommendations in this article apply to this group.
• c.7271T>G (p.Val2424Gly) variant: A particular change that has a dominant disruptive effect on the gene's function. Because breast cancer risk with this variant can approach 60% by age 80, surveillance similar to that for BRCA is planned.
• Variant of uncertain significance (VUS): A change whose effect on cancer risk is unknown. It is often reclassified as ‘harmless’ over time. Screening or treatment is not changed based on a VUS result; surveillance is planned according to family history (germline variant analysis).
• ATM change detected only in the tumor: A change found in tumor tissue (somatic) may not be inherited; whether it has implications for the family should be confirmed separately through a blood or saliva test.

Which Cancer Risks Does an ATM Mutation Increase?

The rates below are estimates of lifetime risk up to age 80 for people carrying a pathogenic ATM variant. These are averages; age, family history, breast density, hormonal factors and lifestyle can substantially increase or decrease an individual's risk.

Breast Cancer

The BCAC study of approximately 113 thousand women and the CARRIERS study of 64 thousand women (both NEJM, 2021) showed that women carrying an ATM variant have approximately twice the risk of breast cancer (relative risks 2.10 and 1.82, respectively). This increase mainly concerns hormone receptor-positive breast cancer; there is no significant increase in hormone receptor-negative breast cancer, including triple-negative disease. For comparison, lifetime breast cancer risk in BRCA1 and BRCA2 carriers reaches 60–70%.

Tools such as CanRisk can help personalize risk estimates by considering family history, breast density and lifestyle. However, these tools may underestimate risk with particular variants such as c.7271T>G. Alcohol, body weight and inactivity are important modifiable factors for carriers as well (How Preventable Is Breast Cancer?).

Pancreatic Cancer

In ATM carriers, pancreatic cancer risk is approximately 4–8 times that of the general population, with an estimated lifetime risk of 5–10%. In a study of people with a family history of pancreatic cancer, ATM carriers had a 6.5-fold increased risk and a 9.5% risk by age 80 (JAMA Oncology, 2021). This still means that the vast majority of carriers will not develop pancreatic cancer. Not smoking, limiting alcohol and maintaining a healthy weight are the most important steps to reduce risk (Smoking and Cancer).

Prostate Cancer

Men carrying an ATM variant have an increased risk of prostate cancer, and some studies suggest an association with more aggressive disease; however, the magnitude of the risk is not yet clear.

Ovarian and Other Cancers

Ovarian cancer risk is slightly increased (2–3%, compared with 1–2% in the general population); this increase is below the threshold for preventive surgery. A small increase in stomach cancer risk has been reported, which may be particularly important when combined with H. pylori infection. No significant ATM-related risk increase has been established for colorectal, skin or other cancers; screening for these cancers is planned according to family history.

Risk Management for ATM Carriers

When an ATM variant is identified, consultation with a genetic counselor or an oncology team experienced in hereditary cancer is recommended to evaluate family history and develop an individual plan. The recommendations below summarize the ACMG (2024) and NCCN (2026) guidelines.

Pancreatic Screening: For Whom and How?

Although screening for early pancreatic cancer detection is promising in high-risk people, it has not yet been shown to prolong survival; it also has drawbacks, such as unnecessary operations and anxiety. Guidelines therefore differ: NCCN states that surveillance may be considered for ATM carriers from age 50, while some guidelines recommend it only for people with a first- or second-degree relative with pancreatic cancer. The decision should be made at an experienced center after discussing screening's limitations, cost, risks and benefits. New-onset or inexplicably worsening diabetes may be a warning sign warranting pancreatic evaluation (Studies on Early Pancreatic Cancer Detection).

Preventive Surgery: The Difference from BRCA

For BRCA carriers, preventive mastectomy and removal of the ovaries are recommended as lifesaving options (Preventive Surgery in BRCA Carriers). For ATM carriers, because the risk is lower, these operations are not routinely recommended; regular MRI and mammography surveillance is considered sufficient for most women. For women with a very strong family history, this option may be discussed along with its advantages and disadvantages.

Family and Reproductive Planning

• Testing Family Members: Each of a carrier's parents, siblings and children has a 50% chance of carrying the same variant. A targeted test looking only for the family's specific variant is sufficient. Testing is generally performed after age 18 at the individual's own decision, because screening associated with carrier status begins in adulthood.
• Partner Testing: Both parents must be carriers for ataxia-telangiectasia to occur. Marriage between relatives substantially increases this probability. Testing the partner of a carrier who is planning children should be discussed together with genetic counseling.
• Reproductive Options: If both partners are carriers, options include genetic testing of embryos during IVF (preimplantation genetic diagnosis) or prenatal diagnosis during pregnancy.

Treatment in ATM Carriers Diagnosed with Cancer

Cancer treatment for ATM carriers is largely the same as for non-carriers. An inherited ATM change can affect treatment decisions in a few specific respects.

Breast Cancer Surgery

Breast-conserving surgery (removing the lump and radiotherapy) is a safe option for women who are ATM carriers and have been diagnosed with breast cancer. According to the ACMG guideline, removing the other breast as well (bilateral mastectomy) is not routinely necessary; the decision should be made jointly with the patient, considering individual factors such as age, tumor stage, grade, hormone receptor status and family history. The risk of a new cancer in the opposite breast is lower than in BRCA carriers, but the exact rate is not yet well known.

Is Radiotherapy Safe?

Because people with ataxia-telangiectasia are extremely sensitive to radiation, it was debated for many years whether radiotherapy might also cause more adverse effects or second cancers in people carrying a change in one copy. Current data show that carriers tolerate radiotherapy well. The ACMG guideline is clear: when radiotherapy is needed, it should not be avoided because of ATM carrier status; the genetic result should not influence the radiotherapy decision. Likewise, no evidence shows that mammography or other X-ray examinations harm carriers.

PARP Inhibitors: What Should Be Expected in ATM?

PARP inhibitors block an enzyme involved in DNA repair, targeting cancer cells whose repair systems are already impaired. Their greatest benefit has been shown in cancers with BRCA1 and BRCA2 mutations (olaparib). The picture is more complex for ATM:

• Prostate cancer: In the United States, olaparib (2020) and the combination of talazoparib + enzalutamide (2023) are approved for metastatic castration-resistant prostate cancer with changes in homologous recombination repair genes, including ATM. However, most of the benefit in these studies comes from patients with BRCA mutations; the ACMG guideline states that PARP inhibitors are probably ineffective in prostate tumors driven solely by ATM. In Europe, approvals for these drugs are limited to patients with BRCA mutations (Olaparib in BRCA-Mutant Prostate Cancer).
• Ovarian cancer: PARP inhibitor approvals in ovarian cancer are based on a BRCA mutation or homologous recombination deficiency in the tumor (HRD testing). For a woman carrying an ATM variant, use of these drugs is determined by these tests and the treatment response, not by the ATM result. Some late-line PARP inhibitor indications mentioned in our previous article were withdrawn in 2022 (Who Benefits from PARP Inhibitors?).
• Breast and pancreatic cancer: Olaparib approvals in breast cancer (metastatic and early-stage disease) and pancreatic cancer apply only to people with inherited BRCA mutations; there is insufficient evidence for ATM.

Cancer patients carrying an ATM variant can therefore ask their oncologists whether there are clinical trials targeting ATM in their cancer type; the benefit expected from PARP inhibitors should not be as great as in BRCA carriers.

What Does This Mean in Practice?

• Read the result correctly: Is it a pathogenic variant, a variant of uncertain significance, or a change detected only in the tumor? Recommendations differ accordingly.
• Assess risk realistically: ATM is not BRCA. Most women carrying an ATM variant do not develop breast cancer; however, regular screening provides a high chance of finding cancer early if it develops.
• Individualize the screening plan: Family history, age and breast density alter risk estimates; tools such as CanRisk can calculate individual risk.
• Do not fear radiation: Mammography, CT scans and radiotherapy when needed are safe for carriers.
• Inform the family: Testing close relatives enables an appropriate surveillance plan for them as well.

Practical Suggestions for Carriers and Their Relatives

• Keep your genetic test report and show it to all your physicians; note the variant's full name, such as c.7271T>G.
• If you are a woman, discuss annual breast MRI starting at age 30–35 and annual mammography starting at age 40 with your physician; report breast changes, such as a lump, nipple discharge or skin retraction, without delay.
• If you are a man, consult your urologist or oncologist about annual PSA testing from age 40.
• Do not smoke, limit alcohol, maintain a healthy weight and exercise regularly; these steps reduce breast and pancreatic cancer risk.
• If you develop new-onset diabetes or unexplained weight loss, remind your physician that you are an ATM carrier.
• If you are planning children, particularly if you and your partner are related, discuss partner testing with your genetic counselor.
• If you have a variant of uncertain significance (VUS), ask the laboratory every few years whether it has been reclassified.

Frequently Asked Questions

Will I Definitely Develop Cancer if I Carry an ATM Mutation?

No. Approximately 70–80% of women carrying an ATM variant do not develop breast cancer during their lifetime; pancreatic cancer risk is around 5–10%. Risk is increased, but cancer is not inevitable. Regular screening offers a high chance of detecting cancer early if it develops.

Should Women Carrying an ATM Variant Have Preventive Mastectomy?

It is not routinely recommended. Annual breast MRI and mammography surveillance is considered sufficient for most women carrying an ATM variant. For people with a very strong family history or high-risk variants such as c.7271T>G, this option may be discussed individually.

Do Mammography and Radiotherapy Harm ATM Carriers?

No. There is no evidence that mammography or radiotherapy harms people carrying a change in one ATM copy. When radiotherapy is needed, it should not be avoided because of ATM carrier status. Extreme radiation sensitivity is specific to people with ataxia-telangiectasia who have changes in both copies.

Can I Pass an ATM Mutation to My Children?

Each of your children has a 50% chance of carrying the same change. Your partner must also be a carrier for your child to have ataxia-telangiectasia; in that case, the probability is 25% in each pregnancy. Seek genetic counseling if you are planning children.

Glossary

ATM gene

A gene that detects severe DNA damage and initiates repair; located on chromosome 11.

Carrier (heterozygous)

A person carrying a change in only one of the two copies of a gene.

Pathogenic variant

A change known to disrupt gene function and increase disease risk; commonly called a ‘mutation’.

Variant of uncertain significance (VUS)

A gene change whose effect on disease risk is not yet known.

Ataxia-telangiectasia

A rare childhood condition caused by changes in both ATM gene copies, involving impaired balance, immunodeficiency and cancer susceptibility.

Homologous recombination

The cellular system that accurately repairs damage in which both DNA strands break.

PARP inhibitor

A group of drugs that block the DNA repair enzyme PARP to target cancer cells with impaired repair.

Preimplantation genetic diagnosis

Genetic testing of embryos during IVF before they are placed in the uterus.