The first dedicated clinical report of breast cancer characteristics in women with pathogenic POT1 variants suggests that enhanced surveillance may deserve further investigation.
An Israeli multicenter study published on July 10, 2026, has raised an important new question in hereditary cancer genetics: could pathogenic variants in the POT1 gene increase the risk of breast cancer in some women?
The report, published in Familial Cancer, is the first study focused specifically on the clinical characteristics of breast cancer among POT1 variant carriers.
POT1 helps protect telomeres, the structures at the ends of chromosomes.
Pathogenic germline variants in the gene are already associated with a tumor-predisposition syndrome that may include melanoma, chronic lymphocytic leukemia, sarcoma, glioma, and papillary thyroid cancer.
Until now, breast cancer has not been considered a well-established part of this syndrome.
What the researchers observed
The team reviewed a cohort of 29 women carrying pathogenic POT1 variants.
Thirteen women, or 45% of the cohort, had been diagnosed with breast cancer, accounting for 14 primary breast cancer events.
Eleven of the 13 affected women carried the POT1 c.233T>C variant, described as an Ashkenazi Jewish founder variant.
The median age at first breast cancer diagnosis was 54 years, with a range of 44 to 72.
All primary tumors with available receptor data were estrogen receptor-positive. No triple-negative breast cancers were observed.
Six of ten tumors with known stage were diagnosed at stage 0 or I.
During a median follow-up of 110 months among patients with available data, three second breast cancer events occurred, but there were no breast-cancer-related deaths.
The study was conducted across major Israeli centers, including Hadassah, Rabin, Sheba, Soroka, Rambam, and affiliated universities.
This broad collaboration is particularly relevant for rare hereditary variants, for which meaningful clinical patterns can be difficult to identify at a single institution.
Why caution is essential
The findings do not prove that POT1 variants cause a high lifetime risk of breast cancer.
The cohort was small, clinical data were incomplete for some patients, and the women were not drawn from a population-based screening sample. The observed 45% frequency therefore cannot be used as a general risk estimate for all POT1 carriers.
The researchers suggest that enhanced breast surveillance, potentially including MRI in selected carriers, may warrant consideration—especially for women with the Ashkenazi founder variant and a significant personal or family history.
However, they emphasize that larger studies are needed to determine lifetime risk, define appropriate screening ages, and establish evidence-based recommendations.
The current evidence does not support preventive bilateral mastectomy based on POT1 status alone.
For patients with a complex personal or family cancer history, Sapir Medical Clinic can coordinate consultations with Israeli oncogenetics specialists, review previous genetic testing, and help arrange a personalized screening or second-opinion pathway.
Genetic results should always be interpreted by a qualified specialist in the context of the patient’s complete personal and family history.
If you would like to receive medical treatment in Israel using the most advanced technologies and latest innovations, with leading doctors at Israel’s top hospitals, contact Sapir Medical Clinic: info@sapirmedical.com