Background Progesterone receptor (PR)-negative tumors have been shown to have worse prognosis and were underrepresented in recent trials on patients with estrogen receptor (ER)-positive breast cancer. The role of PR-negative status in the context of 21-gene recurrence score (RS) and nodal staging remains unclear. Methods The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer. Logistic and Cox multivariable analyses (MVA) were performed to identify association of PR status with high RS (> 25) and overall survival (OS), respectively. Results Among 143,828 women, 130,349 (90.6%) and 13,479 (9.4%) patients had PR-positive and PR-negative tumors, respectively. Logistic MVA showed that PR-negative status was associated with higher RS (> 25: aOR 16.15, 95% CI 15.23–17.13). Cox MVA showed that PR-negative status was associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10–1.31). There was an interaction with nodal staging and chemotherapy (p = 0.049). Subgroup analyses using Cox MVA showed the magnitude of the chemotherapy benefit was greater among those with pN1a, PR-negative tumors than pN1a, PR-positive tumors (PR-positive: aHR 0.57, 95% CI 0.47–0.67; PR-negative: aHR 0.31, 95% CI 0.20–0.47). It was comparable among those with pN0 tumors regardless of PR status (PR-positive: aHR 0.74, 95% CI 0.66–0.82; PR-negative: aHR 0.63, 95% CI 0.51–0.77). Conclusion PR-negative tumors were independently correlated with higher RS and were associated with greater OS benefits from chemotherapy for pN1a tumors, but not pN0 tumors.

ImportanceWhile low income has been associated with a higher incidence of triple-negative breast cancer, its association with 21-gene recurrence score (RS) among patients with estrogen receptor (ER)-positive breast cancer remains unclear.ObjectiveTo evaluate the association of household income with RS and overall survival (OS) among patients with ER-positive breast cancer.Design, Setting, and ParticipantsThis cohort study used data from the National Cancer Database. Eligible participants included women diagnosed between 2010 and 2018 with ER-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy with or without chemotherapy. Data analysis was performed from July 2022 to September 2022.ExposuresLow vs high neighborhood-level household income levels defined as below vs above the median household income of $50 353 based on each patient’s zip code.Main Outcomes and MeasuresRS (a score ranged from 0 to 100 based on gene expression signatures indicating the risk of distant metastasis, with RS of 25 or below indicating non–high risk and RS above 25 indicating high risk) and OS.ResultsAmong 119 478 women (median [IQR] age, 60 [52-67] years; 4737 [4.0%] Asian and Pacific Islander, 9226 [7.7%] Black, 7245 [6.1%] Hispanic, 98 270 [82.2%] non-Hispanic White), 82 198 (68.8%) and 37 280 (31.2%) patients had high and low income, respectively. Logistic multivariable analysis (MVA) showed that, compared with high income, low income was associated with higher RS (adjusted odds ratio [aOR], 1.11; 95% CI, 1.06-1.16). Cox MVA showed that low income was also associated with worse OS (adjusted hazards ratio [aHR], 1.18; 95% CI, 1.11-1.25). Interaction term analysis showed a statistically significant interaction between income levels and RS (interaction P < .001). On subgroup analysis, significant findings were noted among those with RS below 26 (aHR, 1.21; 95% CI, 1.13-1.29), while there was no significant OS difference between income levels among others with RS of 26 or higher (aHR, 1.08; 95% CI, 0.96-1.22).Conclusions and RelevanceOur study suggested that low household income was independently associated with higher 21-gene recurrence scores and significantly worse survival outcomes among those with scores below 26, but not 26 or higher. Further studies are warranted to investigate the association between socioeconomic determinants of health and intrinsic tumor biology among patients with breast cancer.

IMPORTANCE National guidelines allow consideration of postoperative radiation therapy (PORT)among patients with incompletely resected non-small cell lung cancer (NSCLC). However, there is a paucity of prospective data because recently completed trials excluded patients with positive surgical margins. In addition, unlike for locally advanced NSCLC, the role of intensity-modulated radiation therapy (IMRT) for PORT remains unclear. OBJECTIVETo evaluate trends of IMRT use for PORT in the US and the association of IMRT with survival outcomes among patients with incompletely resected NSCLC. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data from the National Cancer Database for patients diagnosed between January 2004 and December 2019 with incompletely resected NSCLC who underwent upfront surgery with positive surgical margins followed by PORT. EXPOSURES IMRT vs 3D conformal radiation therapy (3DCRT) for PORT. MAIN OUTCOMES AND MEASURES The main outcome was overall survival. Multivariable Cox proportional hazards regression assessed the association of IMRT vs 3DCRT with overall survival. Multivariable logistic regression identified variables associated with IMRT. Propensity score matching (1:1) was performed based on variables of interest. RESULTS A total of 4483 patients (2439 men [54.4%]; median age, 67 years [IQR, 60-73 years])were included in the analysis. Of those, 2116 (47.2%) underwent 3DCRT and 2367 (52.8%) underwent IMRT. Median follow-up was 48.5 months (IQR, 31.1-77.2 months). The proportion of patients who underwent IMRT increased from 14.3% (13 of 91 patients) in 2004 to 70.7% (33 of 471 patients) in 2019 (P < .001). IMRT was associated with improved overall survival compared with 3DCRT (adjusted hazard ratio, 0.84; 95% CI, 0.78-0.91; P < .001). Similar findings were observed for 1463 propensity score-matched pairs; IMRT was associated with improved 5-year overall survival compared with 3DCRT (37.3% vs 32.2%; hazard ratio, 0.88; 95% CI, 0.80-0.96; P = .003). IMRT use was associated with receipt of treatment at an academic facility (adjusted odds ratio [aOR], 1.15; 95%

529 Background: Among patients with estrogen receptor (ER)-positive breast cancer, progesterone receptor (PR)-negative tumors were shown to have worse prognosis than PR-positive tumors. However, PR-negative tumors were underrepresented in trials such as TAILORx and RxPONDER, and the role of PR status in the setting of 21-gene recurrence score (RS) remains unclear. We performed an observational cohort study to evaluate the association of PR status with RS and the magnitude of chemotherapy benefits on survival. Methods: The National Cancer Database (NCDB) was queried for women diagnosed between 2010 and 2017 with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1-3N0-1a breast cancer who underwent surgery and endocrine therapy. Logistic and Cox multivariable analyses (MVA) were used to identify variables associated with high RS (> 25) and overall survival (OS), respectively. Interaction test was performed among PR status, chemotherapy, and nodal staging. Propensity score matching was performed to reduce selection bias. Sensitivity analysis was performed after excluding those with postdiagnosis survival of less than 6 months to reduce immortal time bias. Results: A total of 143,828 patients met our criteria (n = 110,421 for PR-positive/pN0, n = 11,897 for PR-negative/pN0, n = 19,928 for PR-positive/pN1a, n = 1,582 for PR-negative/pN1a). Median follow up was 51.5 months (interquartile range 34.8-71.9). On logistic MVA, PR-negative tumors were more likely to have high RS (adjusted odds ratio [aOR] 6.68, 95% confidence interval [CI] 6.40-6.97, p < 0.001). On Cox MVA, PR-negative tumors were associated with worse OS (adjusted hazards ratio [aHR] 1.20, 95% CI 1.10-1.31, p < 0.001). Interaction among PR status, chemotherapy, and nodal staging was statistically significant (interaction p = 0.049). On subgroup analyses, the magnitude of chemotherapy benefit for OS was comparable among pN0 tumors (PR-positive: aHR 0.74, 95% CI 0.66-0.82; PR-negative: aHR 0.63, 95% CI 0.51-0.77) and was greater for PR-negative status among pN1a tumors (PR-positive: aHR 0.57, 95% CI 0.47-0.67; PR-negative: aHR 0.31, 95% CI 0.20-0.47). Similar findings were noted in 9,979, 1,822, 4,196, and 354 matched pairs for PR-positive/pN0 (HR 0.43, 95% CI 0.37-0.50), PR-negative/pN0 (HR 0.53, 95% CI 0.41-0.69), PR-positive/pN1a (HR 0.55, 95% CI 0.45-0.67), and PR-negative/pN1a (HR 0.25, 95% CI 0.14-0.45) tumors, respectively. On sensitivity analysis, our findings were consistent in Cox MVA using interaction and subgroup analyses. Conclusions: To our knowledge, this is the largest study using a nationwide oncology database suggesting that PR-negative status is an independent, adverse prognostic factor for survival associated with high RS, with greater chemotherapy benefits compared to PR-positive status among pN1a tumors even after adjusting for RS.

511 Background: Despite studies on racial/ethnic disparities in breast cancer patients, there is limited literature evaluating association of racial/ethnic differences with 21-gene recurrence score (RS) and survival differences stratified by RS risk categories. We performed an observational cohort study to evaluate such disparities in context of RS. Methods: The National Cancer Database (NCDB) was queried for patients with ER-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy with available RS from 2006 to 2018. Racial/ethnic groups were stratified by non-Hispanic White (NHW), Hispanic White (HW), Black, and Asian/Pacific Islander (API). Our primary endpoint was overall survival (OS). Logistic multivariable analysis (MVA) was built upon baseline patient and tumor characteristics to evaluate variables associated with RS > 25. Cox MVA was used to evaluate OS. Interaction term analysis was used to identify heterogeneous association of racial/ethnic groups and RS; if significant, subgroup analyses compared magnitude of racial/ethnic differences stratified by RS. To address immortal time bias, Cox MVA analyses were repeated after excluding patients with post-diagnosis survival < 6 months. P values were two-sided. Bonferroni correction was used for multiple comparisons (NHW vs HW women, NHW vs Black women, and NHW vs API women) with p values less than 0.017 being statistically significant. Results: A total of 140,133 women (median [interquartile range (IQR)] age, 60 [52-67] years) were included for analysis. 115,651 (82.5%), 8,213 (5.9%), 10,814 (7.7%), and 5,455 (3.9%) were NHW, Hispanic, Black, and API women respectively. Median (IQR) follow up was 66.2 mo. (48.0-89.8). Logistic MVA showed compared to NHW women, Black women were associated with higher RS (26 or higher vs < 26: adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12-1.26, p < 0.001), while HW (aOR 0.93, 95% CI 0.86-1.00, p = 0.04) and API (aOR 1.03, 95% CI 0.95-1.13, p = 0.45) were not. Cox MVA showed compared to NHW, Black women were associated with worse OS (adjusted hazards ratio [aHR] 1.10, 95% CI 1.02-1.19, p = 0.012) while HW (aHR 0.85, 95% CI 0.77-0.94, p = 0.001) and API (aHR 0.66, 95% CI 0.56-0.77, p < 0.001) were not. There was significant interaction between race/ethnicity and RS (interaction p = 0.006). Subgroup analysis found similarities in those with RS < 26, while only API women were associated with improved OS among those with RS ≥ 26. After excluding those with post-diagnosis survival < 6 mo., our findings remained comparable. Conclusions: To our knowledge, this is the largest nationwide oncology database study to suggest that Black women are associated with higher RS, while HW and API are not. It also suggests that Black women are associated with worse OS among those with RS < 26, while API are associated with improved OS regardless of RS compared to NHW women.