Interval Breast Cancer Appears Genetically Distinct From Screen-Detected Breast Cancer

Interval breast cancers and screen-detected breast cancers have distinct genetic profiles, according to research published in JAMA Oncology.

Researchers found that germline deleterious protein-truncating variants (PTVs) in ATM, BRCA1, BRCA2, CHEK2, and PALB2 were more common in patients with interval breast cancers, and these patients were more likely to have a relative with breast cancer.

For this study, researchers compared 4121 breast cancer patients (aged 40 to 76 years) to 5631 age-matched control individuals who underwent mammographic screening in Sweden. The researchers also compared 1229 patients diagnosed with interval breast cancer to 2892 patients with screen-detected breast cancer.

Overall, the breast cancer patients were more likely than control individuals to have PTVs in any of the 34 breast cancer genes examined (odds ratio [OR], 2.04; 95% CI, 1.70-2.44). In particular, PTVs in the 5 major genes for breast cancer (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were significantly more likely in breast cancer patients than in matched control individuals (OR, 2.62; 95% CI, 2.02-3.40).

Patients with interval breast cancer were significantly more likely than those with screen-detected breast cancer to have PTVs in the 5 major genes (OR, 1.48; 95% CI, 1.06-2.05). This risk was even greater for “true interval cancer,” defined as interval cancer diagnosed after the exclusion of patients with medium or high mammographic density (OR, 1.87; 95% CI, 1.22-2.85).

Patients with any interval breast cancer were more likely to have PTVs for BRCA 1/2 and PALB2 than patients with screen-detected breast cancer (OR, 1.92; 95% CI, 1.17-3.15). However, PTVs in ATM and CHEK2 were not significantly associated with an increased risk of interval breast cancer (OR, 1.24; 95% CI, 0.80-1.92).

Patients diagnosed with interval breast cancer were more likely to report a relative with breast cancer (OR, 1.25; 95% CI, 1.05-1.48). When family history was combined with the presence of PTVs in the 5 major genes, there was a higher risk of any interval cancer (OR, 3.95; 95% CI, 1.97-7.92) and true interval cancer (OR, 5.17; 95% CI, 2.26-11.85).

In an analysis of 3633 patients with breast cancer, those who had PTVs in any of the 5 major genes had worse 10-year breast cancer-specific mortality than patients without these PTVs (hazard ratio [HR], 1.89; 95% CI, 1.08-3.30).

In a fully adjusted model, there was a significant associated between PTVs in the 5 major genes and worse survival for all interval breast cancers (HR, 2.04; 95% CI, 1.06-3.92) and true interval breast cancers (HR, 2.97; 95% CI, 1.07-8.25).

“Our work potentially clarifies the picture of what type of breast cancer is likely to evade detection in population-based screening programs,” the researchers wrote. “These insights will possibly be helpful in future optimizations of screening programs aimed at lowering mortality, as well as the clinical treatment of patients with BC [breast cancer].”

This article originally appeared on Cancer Therapy Advisor