PAM50 and risk of recurrence scores for interval breast cancers

Breast cancers detected after a negative breast screening examination and prior to the next screening are referred to as interval cancers. These cancers generally have poor clinical characteristics compared to screen-detected cancers, but associations between interval cancer and genomic cancer characteristics are not well understood. Mammographically-screened women diagnosed with primary invasive breast cancer from 1993-2013 (n=370) were identified by linking the Carolina Breast Cancer Study and the Carolina Mammography Registry. Among women with a registry-identified screening mammogram 0-24 months before diagnosis, cancers were classified as screen-detected (N=165) or interval-detected (N=205). Using logistic regression, we examined the association of mode of detection with cancer characteristics (clinical, IHC, and genomic), overall, and in analyses stratified on mammographic density and race. Interval cancer was associated with large tumors (> 2 cm) (OR=2.3; 95% C.I.: 1.5, 3.7), positive nodal status (OR=1.8; 95% C.I.: 1.1, 2.8), and triple negative subtype (OR=2.5; 95% C.I.: 1.1, 5.5). Interval cancers were more likely to have non-Luminal A subtype (OR=2.9; 95% C.I.: 1.5, 5.7), while screen-detected cancers tended to be more indolent (96% had low risk of recurrence genomic scores; 71% were PAM50 Luminal A). When stratifying by mammographic density and race, associations between interval detection and poor prognostic features were similar by race and density status. Strong associations between interval cancers and poor-prognosis genomic features (non-Luminal A subtype and high risk of recurrence score) suggest that aggressive tumor biology is an important contributor to interval cancer rates.

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