Synchronous Contralateral Breast Cancer Detected at Elective Bilateral Mastectomy: Incidence, Predictors, and Biomarker Concordance in the National Cancer Database.

PURPOSE: To determine the incidence and characteristics of synchronous contralateral breast cancer (SCBC) detected at elective bilateral mastectomy for unilateral breast cancer using the National Cancer Database (NCDB), and to identify factors associated with contralateral disease.

MATERIALS AND

METHODS

We performed a retrospective analysis of the NCDB Participant Use File (2022-2023) using newly introduced breast-specific surgery codes identifying bilateral mastectomy with contralateral removal. Patients with unilateral breast cancer who underwent bilateral mastectomy were identified (n = 13,931). SCBC was defined conservatively as SEQUENCE_NUMBER=01. Multivariable logistic regression with stepwise selection identified independent predictors. Probabilistic matching enabled concordance analysis of 336 paired tumors.

RESULTS

Among 13,931 patients, 709 had SCBC (incidence 5.09%). Mean age was 57.7 ± 12.3 years. Most primary tumors were invasive (81.4%), HR+/HER2- (64.5%), node-negative (64.0%), and stage 0-IA (56.0%). Age was the strongest predictor, with 6.7-fold higher odds in patients ≥ 70 versus < 40 (odds ratios [OR] 6.68, 95% confidence intervals [CI], 4.58-9.76, P < .0001). Compared with HR+/HER2- tumors, other subtypes carried lower odds, with triple-negative disease lowest (OR 0.48, 95% CI, 0.35-0.65, P < .0001). Primary tumor size was not associated with SCBC (OR 1.001, P = .20). Discrimination was modest (c-statistic 0.669). In 336 matched pairs, contralateral tumors were smaller (median 11.5 mm vs. 18.5 mm) and predominantly early stage (61% stage 0-IA; 3.3% stage II+). Concordance was 86.8% for ER, 78.8% for HER2, 71.8% for PR, 67.0% for histology, and 42.6% for grade, with full concordance in 40.8%.

CONCLUSION

SCBC is found in approximately 1 in 20 patients undergoing bilateral mastectomy for unilateral disease. Risk is driven by patient-level factors, particularly age and receptor subtype, rather than primary tumor burden. High biomarker discordance supports independent tumor origins and highlights the diagnostic value of contralateral mastectomy specimens in select populations.