Misclassification of second primary and recurrent breast cancer in the surveillance epidemiology and end results registry

The Surveillance Epidemiology and End Results (SEER) registry incorporates laterality, histology, latency, and topography to identify second primary breast cancers. Contralateral tumors are classified as second primaries, but ipsilaterals are subject to additional inclusion criteria that increase specificity but may induce biases. It is important to understand how classification methods affect accuracy of second tumor classification. We collected estrogen, progesterone, and human epidermal growth factor receptor 2 (ER, PR, Her2) status for 11,838 contralateral and 5,371 ipsilateral metachronous secondary tumors and estimated concordance odds ratios (cORs) to evaluate receptor dependence (the tendency for tumors to share receptor status) by laterality. If only second primaries are included, receptor dependence should be similar for contralateral and ipsilateral tumors. Thus, we compared ratios of cORs as a measure of inaccuracy. Cases who met ipsilateral second primary criteria were younger and had less aggressive primary tumor characteristics compared to contralateral tumors. Time to secondary tumors was (by definition) longer for ipsilaterals than contralaterals, especially among ER + primaries. Overall and in multiple strata, ipsilateral tumors showed higher receptor dependence than contralateral tumors (ratios of cORs > 1), suggesting some SEER-included ipsilaterals are recurrences. SEER multiple primary criteria increase specificity, but remain inaccurate and may lack sensitivity. The dearth of early occurring ipsilateral tumors (by definition), coupled with high observed receptor dependence among ipsilaterals, suggests important inaccuracies. Datasets that allow comparison of pathologist- and SEER-classification to true multi-marker genomic dependence are needed to understand inaccuracies induced by SEER definitions.