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Sarah Asad, Carlos H. Barcenas, Richard J. Bleicher, Adam L. Cohen, Sara H. Javid, Ellis G. Levine, Nancy U. Lin, Beverly Moy, Joyce Niland, Antonio C. Wolff, Michael J. Hassett, and Daniel G. Stover

Background: Triple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. Our objective was to evaluate clinicopathologic and sociodemographic features associated with rrTNBC. Methods: We included patients diagnosed with stage I–III TNBC in 1996 through 2012 who received chemotherapy at 1 of 10 academic cancer centers. rrTNBC was defined as a distant metastatic recurrence event or death ≤24 months after diagnosis. Features associated with rrTNBC were included in a multivariable logistic model upon which backward elimination was performed with a P<.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts. Results: Among all patients with breast cancer treated at these centers, 3,016 fit the inclusion criteria. Training cohort (n=2,112) bivariable analyses identified disease stage, insurance type, age, body mass index, race, and income as being associated with rrTNBC (P<.10). In the final multivariable model, rrTNBC was significantly associated with higher disease stage (adjusted odds ratio for stage III vs I, 16.0; 95% CI, 9.8–26.2; P<.0001), Medicaid/indigent insurance, lower income (by 2000 US Census tract), and younger age at diagnosis. Model performance was consistent between the training and validation cohorts. In sensitivity analyses, insurance type, low income, and young age were associated with rrTNBC among patients with stage I/II but not stage III disease. When comparing rrTNBC versus late relapse (>24 months), we found that insurance type and young age remained significant. Conclusions: Timing of relapse in TNBC is associated with stage of disease and distinct sociodemographic features, including insurance type, income, and age at diagnosis.

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Michael J. Hassett, Wei Jiang, Melissa E. Hughes, Stephen Edge, Sara H. Javid, Joyce C. Niland, Richard Theriault, Yu-Ning Wong, Deborah Schrag, and Rinaa S. Punglia

Background: Because of screening mammography, the number of ductal carcinoma in situ (DCIS) survivors has increased dramatically. DCIS survivors may face excess risk of second breast events (SBEs). However, little is known about SBE treatment or its relationship to initial DCIS care. Methods: Among a prospective cohort of women who underwent breast-conserving surgery (BCS) for DCIS from 1997 to 2008 at institutions participating in the NCCN Outcomes Database, we identified SBEs, described patterns of care for SBEs, and examined the association between DCIS treatment choice and SBE care. Using multivariable regression, we identified features associated with use of mastectomy, radiation therapy (RT), or antiestrogen therapy (AET) for SBEs. Results: Of 2,939 women who underwent BCS for DCIS, 83% received RT and 40% received AET. During the median follow-up of 4.2 years, 200 women (6.8%) developed an SBE (55% ipsilateral, 45% invasive). SBEs occurred in 6% of women who underwent RT for their initial DCIS versus 11% who did not. Local treatment for these events included BCS (10%), BCS/RT (30%), mastectomy (53%), or none (6%); only 28% of patients received AET. Independent predictors of RT or mastectomy for SBEs included younger age, shorter time to SBE diagnosis, and RT or AET for the initial DCIS. Conclusions: A sizable proportion of patients with SBEs were treated with mastectomy, most especially those who previously received RT for their initial DCIS and those who developed an ipsilateral SBE. Despite the occurrence of an SBE, relatively few patients received AET. Future studies should investigate optimal treatment approaches for SBEs, including the benefit of mastectomy versus lumpectomy for an ipsilateral SBE and the benefit of AET for a hormone-receptor–positive SBE contingent on AET use for the initial DCIS diagnosis.