Abstract PS15-04: De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer: Patterns of care and survival outcomes using the national cancer database
Authors: Bazan Jose G , Jhawar Sachin , Stover Daniel , Park Ko Un , Beyer Sasha , Healy Erin , White Julia R 
Published: February 2021

Abstract
Background: In the modern era, highly effective anti-HER2 therapy is associated with very low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer. One recent prospective study of T1-2N0 HER2+ breast cancer patients treated with lumpectomy and adjuvant paclitaxel+trastuzumab followed by whole breast radiation (RT) demonstrated 7-year LRR-free survival of 99% raising the question of whether local therapy de-escalation by RT omission is possible. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer.Materials/Methods: We identified patients with stage I (T1N0) HER2+ breast cancer treated with lumpectomy, adjuvant chemotherapy and anti-HER2 therapy from 2013 (the first year anti-HER2 therapy receipt was reliably collected) to 2015. We excluded patients that received neoadjuvant systemic therapy. We then stratified the cohort by receipt of adjuvant RT. The primary endpoint was OS as LRR is not captured by the NCDB. OS was analyzed by the Kaplan-Meier method (RT and RT omission groups compared by the log-rank test) and multivariate cox regression including variables with p&lt;0.20 on univariate analysis (hazard ratios [HR], and 95% confidence intervals [CI] are reported). Propensity score matched (PSM) analysis with patients matched on age (≥70 vs. &lt;70), comorbidities (≥1 vs. 0), grade (3 vs. 1-2), tumor size (&gt;1 cm vs. ≤1 cm), ER/PR status (ER-/PR- vs. ER+ and/or PR+), facility type (academic vs. non-academic), and income (&lt;$46,000/yr vs. ≥46,000/yr) was performed as an independent test of the Cox regression analysis.Results: We identified 6,897 patients that met the study criteria (6,388 RT; 509 no RT). Patients that did not receive RT tended to be older (mean age 64.0 years v. 59.2 years, p&lt;0.0001), have ≥1 comorbidity (21.4% vs. 14.8%, p&lt;0.0001), and live in lower income areas (60.1% vs. 52%, p=0.0004). Median follow-up was 29.4 months (IQR=19.5-39.9 months) with 155 deaths (95 RT; 60 RT omission). The 2-year OS was significantly worse for patients with RT omission (89.0% vs. 99.2%, p&lt;0.0001). Factors associated with OS on univariate analysis included RT omission (p&lt;0.0001), age≥70 (p&lt;0.0001), ≥1 comorbidity (p=0.0002), tumor size&gt;1cm (p=0.14), grade 3 tumors (p=0.14), academic facility (p=0.16) and lower income (p=0.02) but not ER-/PR- status (HR=1.01, p=0.95), distance to treatment facility (p=0.42) or tumor laterality (p=0.66). On multivariate analysis, RT omission (HR=7.55, 95% CI 5.36-10.63, p&lt;0.0001), age≥70 (HR=2.30, 95% CI 1.63-3.23, p&lt;0.0001), and ≥1 comorbidity (HR=1.45, 95% CI 1.00-2.09, p=0.05) remained independently associated with higher risk of death. The PSM cohort consisted of 509 pairs of patients with 73 deaths (13 RT; 60 RT omission) and median follow-up 26.4 months (IQR, 16.5-37.3 months). RT omission remained associated with a 5.42-fold (95% CI 3.02-9.73, p&lt;0.0001) increased risk of death in the PSM cohort.Conclusion: This study demonstrates that RT omission is independently associated with an increased risk of death in patients with stage I, HER2+, node-negative breast cancer treated with lumpectomy, adjuvant chemotherapy and anti-HER2 therapy. Patients that did not receive RT tended to be older, have more comorbidities and live in lower income areas. While other selection biases that influence RT omission likely persist, these data should give caution to RT omission in stage I, node-negative HER2+ breast cancer.
Citation Format: Jose G Bazan, Sachin Jhawar, Daniel Stover, Ko Un Park, Sasha Beyer, Erin Healy, Julia R White. De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer: Patterns of care and survival outcomes using the national cancer database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS15-04.