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12-08-2021 | Breast cancer | News

Genetic testing finds pathogenic variants among older breast cancer patients

Author: Lynda Williams


medwireNews: Genetic testing should be expanded to include older women with breast cancer, especially those with triple-negative or estrogen receptor (ER)-negative disease, suggest US researchers.

The US National Comprehensive Cancer Network (NCCN) guidelines suggest that testing for hereditary pathogenic variants (PVs) has “limited clinical utility” in breast cancer patients aged over 65 years without known genetic risk factors as this population is thought to have a less than 2.5% risk of a PV in a high-penetrance gene, explain Fergus Couch (Mayo Clinic, Rochester, Minnesota) and co-workers.

To test this hypothesis, the team analyzed data collated from 12 population-based studies for 13,762 women diagnosed with breast cancer after the age of 65 years and 12,945 unaffected women. The majority of participants were non-Hispanic White (82.6%) and the average age at time of breast cancer diagnosis was 72.8 years.

A quarter (25.6%) of breast cancer patients had a first-degree relative with breast cancer compared with 17.9% of controls, the researchers report in the Journal of Clinical Oncology.

Overall, 3.2% of the breast cancer patients had a PV in a predisposition gene compared with 1.5% of controls. The PV rate was higher in non-Hispanic White and African–American breast cancer patients than their Asian–American counterparts (3.4 each vs 1.2%).

Among women aged over 65 years, PVs in BRCA1, BRCA2, and PALB2 were detected in 3.4% of the 1488 patients with ER-negative breast cancer versus 1.0% of the 9128 patients with ER-positive disease, as well as 3.0% of the 564 women with triple-negative breast cancer (TNBC).

In addition, 4.5% of women who were diagnosed with TNBC after the age of 60 years were positive for a PV in these three high-risk genes, as were 3.3% of women without a family history who were diagnosed with breast cancer after age 60 years.

Couch and co-authors note that women with first-degree relatives with a breast cancer diagnosis were more likely to carry a PV in BRCA1, BRCA2, or PALB2 than those without (2.3 vs 1.0%). And patients with a family history were also more likely to have high-risk PVs than those without regardless of whether they had ER-negative (6.8 vs 2.4%) or ER-positive (1.8 vs 0.7%) disease.

Further analysis indicated that individuals aged over 65 years, with or without a family history of breast cancer, were significantly more likely to be diagnosed with breast cancer if they had a PV in BRCA2 PALB2, or CHEK2 than if they did not carry these PVs, with odds ratios of 4.82, 2.95, and 1.89, respectively.

Using general population data from SEER-21, the absolute lifetime risk for breast cancer for a women aged 66 to 85 years was estimated to be 6.8%. But this rose to 18.4% and 18.7% for women with a PV in BRCA1 or BRCA2, respectively. The corresponding risks for women with a PV in PALB2, CHEK2, or ATM were 15.9%, 14.9%, and 9.9%, respectively.

Couch et al remark that, although women with a PV in a predisposition gene and a lifetime breast cancer risk of 20% or higher are recommended by the NCCN to undergo annual mammograms and MRI screening, “there are no specific guidelines for clinical management of breast cancer in older women.”

Based on the current findings, they now recommend genetic screening for all women diagnosed with TNBC or ER-negative breast cancer.

In addition, women aged over 65 years with a PV in BRCA1 or BRCA2 should be eligible for MRI screening, the authors advise, adding that this approach should also be considered for those with PVs in CHEK2 or PALB2.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

J Clin Oncol 2021; doi:10.1200/JCO.21.00531


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