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The 21-gene recurrence score assay has been validated as a predictive biomarker in early-stage HR+ and HER2-breast cancer. It is not indicated for use in HER2+ disease based on national guidelines. In this study, we assessed the value of 21-gene recurrence score (RS), or OncotypeDX (ODX), testing in HR+/HER2+ breast cancer. We used the National Cancer Database to identify patients with stages I-II, HR+/HER2+ breast cancer who received multi-gene testing with ODX. We then explored the prognostic and predictive value of this biomarker through various forms of survival modeling. ODX testing was performed in n = 5,280 patients. N = 2,678 patients (50.7%) had a RS < 26, while n = 2,602 (49.3%) had a RS ≥26. In Kaplan-Meier survival modeling for patients with recurrence scores <26, there was no significant difference in overall survival (p = 0.445) between patients receiving different systemic treatment regimens. However, when recurrence scores were ≥26, there was a statistically-significant difference in overall survival between systemic treatment regimens (p < 0.001). 5-year overall survival was highest (97.4%) for patients receiving triple therapy (anti-HER2 with chemotherapy and endocrine therapy), followed by those receiving dual therapy with endocrine and anti-HER2 (96.7%), and endocrine with chemotherapy (94.9%). Patients receiving endocrine therapy alone exhibited the lowest 5-year overall survival (88.5%). Analysis from this large national cancer registry suggests that multigene testing may have predictive value in treatment selection for patients with early-stage, HR+/HER2+ breast cancer. Prospective trials are warranted to identify subgroups of patients with HR+/HER2+ breast cancer who can be spared anti-HER2 treatments and cytotoxic chemotherapy. • 21-gene recurrence scoring prognosticates survival in stage I-II HR+/HER2+ disease. • There was no difference in survival by systemic regimen with recurrence scores <26. • In high-risk disease, endocrine therapy alone exhibited inferior survival. • Treatment de-escalation may be safe in HER2+ disease with low risk of recurrence. [ABSTRACT FROM AUTHOR]

Treatment protocols for invasive lobular breast cancer (ILC) have largely followed those for invasive ductal breast cancer. This study compares treatment outcomes of endocrine therapy versus combined chemo-endocrine therapy in hormone-receptor-positive (HR+), HER2-positive (HER2+) ILC tumors in a large national registry. We sampled the National Cancer Database (2010–2016) for female patients with stages I-III, HR+/HER2+ ILC who underwent surgery. Cochran-Armitage trend test examined trends of treatment regimen administration: Surgery only (S), chemotherapy (C), endocrine therapy (ET), and combined chemo-endocrine therapy (CET), with or without anti-HER2 therapy. Cox proportional hazard model were used to compare overall survival (OS) across ET and CET cohorts, stratifying for anti-HER2 therapy, before and after propensity score match of cohorts (2013–2016). Kaplan-Meier (KM) survival curves were also produced. N =11,421 were included. 58.7% of patients received Anti-Her2 therapy after 2013. CET conferred better OS over ET in the unmatched (adjusted-5-year-OS: 92.5% vs. 81.1%, p<0.001 ) and PS-matched (90.4% vs. 84.5%, p=0.001 ) samples. ET caused lower OS in patients who received Anti-Her2 therapy (HR: 2.56, 95% CI: 1.60–4.12, p<0.001 ) and patients who did not (HR: 1.84, 95% CI: 1.21–2.78, p=0.004 ), as compared to CET on multivariable analysis. KM modeling showed highest OS in the CET cohort who received Anti-Her2 (93.0%), followed by the CET cohort who did not receive Anti-Her2 (90.2%) ( p=0.06 ). Chemotherapy followed by endocrine therapy and Anti-Her2 therapy was shown to be the most effective treatment modality in HR+/HER2+ ILC, contrasting previous data on the inconclusive benefit of chemotherapy in patients with ILC. • Less chemotherapy (CT) is used in favor of endocrine therapy (ET) alone for HR+/HER2+ ILBC at the expense of efficacy. • CT followed by ET remains an effective treatment in HR+/HER2+ ILBC, specifically for larger and locally advanced tumors. • Research investigating subgroups of lobular BC who would benefit from CT de-escalation, or ET alone without CT is needed. [ABSTRACT FROM AUTHOR]

Locoregional therapy at primary or secondary sites in breast cancer may be associated with improved survival as compared to systemic therapy alone. We explored the sociodemographic and clinicopathologic factors associated with the use of radiation versus surgical resection of metastatic sites (metastasectomy) in patients with de novo stage IV breast cancer, followed by the associated overall survival. We sampled the National Cancer Database for patients with de novo stage IV breast cancer, (2010–2017) and described cohort's characteristics using univariate analyses. We identified 5 subgroups based on malignant site involvement: 1. Bone only, 2. Brain only, 3. Liver only, 4. Lung only, and 5. Metastasis involving >1 site. Kaplan-Meier modeling with log-rank testing and multivariate Cox Regression analysis were used to explore differences in overall survival between those that received radiation at secondary sites and those that underwent metastasectomy. N = 22,749patients were included in this analysis. Radiation (81.2%) was used more commonly than metastasectomy (28.8%). Metastasectomy was associated with better median overall survival across all 5 cohorts (p <.001), with the survival benefit being the most pronounced with lung only (OS: 56.9 months; HR 0.8, 95% CI 0.7–0.9, p =.032), or liver only (OS: 41.6 months; HR: 0.9; 95% CI: 0.7–1.1, p <.001) metastasis. Metastasectomy in patients with de novo stage IV breast cancer may be associated with improved overall survival as compared to radiation of secondary lesions, particularly in those with only liver or lung involvement. Prospective randomized controlled trials investigating surgical resection of metastatic sites in patients with breast cancer are warranted. • Metastasectomy in Stage IV breast cancer leads to improved survival regardless of organ involvement and number of lesions. • The survival benefit of metastasectomy is most apparent when the breast cancer metastasis involves the liver or the lung. • Radiation and metastasectomy should be considered for treatment of secondary breast cancer lesions in clinical practice. [ABSTRACT FROM AUTHOR]

dNLR at the baseline (B), defined by neutrophils/[leucocytes-neutrophils], correlates with immune-checkpoint inhibitor (ICI) outcomes in advanced non–small-cell lung cancer (aNSCLC). However, dNLR is dynamic under therapy and its longitudinal assessment may provide data predicting efficacy. We sought to examine the impact of dNLR dynamics on ICI efficacy and understand its biological significance. aNSCLC patients receiving ICI at 17 EU/US centres were included [Feb/13-Jun/18]. As chemotherapy-only group was evaluated (NCT02105168). dNLR was determined at (B) and at cycle2 (C2) [dNLR≤3 = low]. B+C2 dNLR were combined in one score: good = low (B+C2), poor = high (B+C2), intermediate = other situations. In 57 patients, we prospectively explored the immunophenotype of circulating neutrophils, particularly the CD15+CD244-CD16 low cells (immature) by flow cytometry. About 1485 patients treatment with ICI were analysed. In ICI-treated patients, high dNLR (B) (~1/3rd) associated with worse progression-free (PFS)/overall survival (OS) (HR 1.56/HR 2.02, P < 0.0001) but not with chemotherapy alone (N = 173). High dNLR at C2 was associated with worse PFS/OS (HR 1.64/HR 2.15, P < 0.0001). When dNLR at both time points were considered together, those with persistently high dNLR (23%) had poor survival (mOS = 5 months (mo)), compared with high dNLR at one time point (22%; mOS = 9.2mo) and persistently low dNLR (55%; mOS = 18.6mo) (P < 0.0001). The dNLR impact remained significant after PD-L1 adjustment. By cytometry, high rate of immature neutrophils (B) (30/57) correlated with poor PFS/OS (P = 0.04; P = 0.0007), with a 12-week death rate of 49%. The dNLR (B) and its dynamics (C2) under ICI associate with ICI outcomes in aNSCLC. Persistently high dNLR (B+C2) correlated with early ICI failure. Immature neutrophils may be a key subpopulation on ICI resistance. • Baseline dNLR (B) and its dynamics (C2) associate with ICI outcome in advanced NSCLC. • The dNLR (B+C2) can improve the prediction of ICI outcomes vs. (B). • The impact of dNLR on survival remained significant after PD-L1 adjustment. • The dNLR is a simple biomarker that should be validated in clinical trials. • Circulating immature neutrophils can be key on ICI resistance. [ABSTRACT FROM AUTHOR]