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The prognostic impact of neutrophil-lymphocyte ratio (NLR) in metastatic breast cancer (MBC) has been previously evaluated in early and metastatic mixed breast cancer cohorts or without considering other relevant prognostic factors. Our aim was to determine whether NLR prognostic and predictive value in MBC was dependent on other clinical variables. We studied a consecutive retrospective cohort of patients with MBC from a single centre, with any type of first line systemic treatment. The association of NLR at diagnosis of metastasis with progression free survival (PFS) and overall survival (OS) was evaluated using Cox univariate and multivariate proportional hazard models. In the full cohort, that included 263 MBC patients, a higher than the median (>2.32) NLR was significantly associated with OS in the univariate analysis (HR 1.36, 95% CI 1.00–1.83), but the association was non-significant (HR 1.12, 95% CI 0.80–1.56) when other clinical covariates (performance status, stage at diagnosis, CNS involvement, visceral disease and visceral crisis) were included in the multivariate analysis. No significant association was observed for PFS. In conclusion, MBC patients with higher baseline NLR had worse overall survival, but the prognostic impact of NLR is likely derived from its association with other relevant clinical prognostic factors.

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e12524 Background: Nodal micrometastatic disease (ypN1mic) after neoadjuvant chemotherapy (nCT) for breast cancer (BC) is considered an indication for axillary lymph node disection. While pN1mic prognostic impact has been extensively studied, the prognostic impact of ypN1mic disease is uncertain and these patients are usually grouped together with nodal macrometastatic disease. Since outcomes may be difficult to evaluate in the setting of BC residual disease, our aim was to compare the prognostic meaning of ypN1mic with that of ypN0 when a pCR is obtained in the breast. Methods: We retrospectively analyzed a series of 454 BC consecutive patients treated between 2010 and 2018 with neoadjuvant chemotherapy (nCT) based on anthracyclines and taxanes (plus antiHER2 treatment when appropriate). Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients with pre-nCT sentinel lymph node biopsy or without post-nCT pathologic evaluation were excluded. Disease free (DFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox regression models. Results: 454 BC patients were included, with 106 (24%) pCR. Median follow-up was 39 months. 99 (21.8%) patients obtained a pCR both in breast and axilla (ypT0/Tis ypN0), with 4 recurrences (4%) while only 7 (1.5%) patients had isolated nodal micrometastatic disease (ypT0/Tis ypN1mic), with 2 recurrences (28%). Median DFS was not reached for the ypN0 group and was 28 months (95%CI: 21.6-34.4 months) for the ypN1mic group (HR: 16.55, 95%cI: 2.68-102.37; p = 0.003). No differences were observed for OS (p = 0.77), although 2/2 ypN1mi showed distant recurrence (2/4 for ypN0 patients). Baseline clinical and pathologic characteristics were comparable between both groups, with no differences in performance status (p = 0.45), clinical nodal stage (p = 0.48), HER2 (p = 0.32), estrogen receptors (p = 0.93), grade (p = 0.34), presence of carcinoma in situ (0.60) or clinical complete response (p = 0.42). Clinical characteristics of patients with recurrence were also similar (100%: clinically positive nodes, negative estrogen receptors, no clinical complete response). Conclusions: Residual nodal micrometastatic disease after nCT seems to be associated with a higher risk of recurrence. Although longer follow-up and larger series are needed to confirm our data, these results support the escalation of post-nCT treatment even in patients with ypN1mic and breast pCR.

e12559 Background: MicroRNAs are involved in cancer biology through their role in regulation of protein expression. The miR-200 family plays a dual role in breast cancer (BC), both regulating epithelial to mesenchymal transition and promoting metastatic colonization. Plasma levels of miR-200 have been previously evaluated as prognostic factors in early and metastatic BC (MBC) but its role as a potential diagnostic marker is less well established. The aim of this study was to determine the potential diagnostic value of miR-200c-3p plasmatic levels in women with locally advanced and metastatic BC. Methods: We included 73 BC patients and 14 controls. Plasma samples were obtained at diagnosis, before treatment. RNA from plasma samples was extracted with NucleoSpin miRNA plasma (Macherey-Nagel). We analyzed expression levels of miR-200c-3p, which were relativized (2-ΔΔCT method) to miR-16. Non-parametric statistical tests were used to determine the association of miR-200c levels with clinical variables. Receiver-operating curves (ROC) were constructed and diagnostic ability evaluated. Kaplan-Meier curves and Cox models were used for survival analyses. Results: 73 BC patients were included: 36 locally advanced BC (LABC) and 37 MBC (7 recurrences and 30 MBC at initial diagnosis [MBCID]). Plasma miR-200c levels were significantly higher in MBC than in controls (p = 0.001) and in LABC (p = 0.001). We found differences neither for age nor for estrogen receptors, HER2, tumor subtype or histology. Overall and disease free survival did not differ by miR-200c levels in any of the groups. Among MBC patients, higher levels were observed in MBCID (p = 0.023). In the group of women with an initial diagnosis of BC (n = 65), high miR-200c levels (over 1st tertile) identified metastatic disease with a sensitivity of 90.0% (95%CI: 72.3-97.4%) and a specificity of 51.4% (95%CI: 34.3-68.3%); negative predictive value: 85.7%; positive predictive value: 61.4%; ROC AUC: 0.79. Conclusions: MiR-200c plasma levels are higher in BC patients with metastatic disease at diagnosis, and might be clinically useful to identify them. Further research on miR200c biological role in MBC and validation in larger populations with sequential samples are warranted.

8070 Background: The majority of lung ADC tumors are characterized by specific genetic features with KRAS mutations (mut) seen in 20-30%, EGFR mut in 15%, EML4-ALK translocations in 5%, and ERBB2 mut in 2%, among others. Some of these genetic alterations are already being used for selecting targeted therapies. However, identification of additional genomic alterations is required. Methods: In the present ongoing study we perform whole-exome sequencing in paraffin-embedded tumor samples from OncoCarta v1.0 panel wild-type (no mut in hotspots of KRAS, EGFR, ERBB2, AKT1, BRAF, PIK3CA genes) and ALK negative (by FISH) stage IV ADC lung cancer p, and in their matched normal tissue samples. Results: To date, a total of 7 tumors and matched normal tissues have been successfully analyzed. We have detected mut in previously identified ADC genes, such as ERBB2, CTNNB1, TP53, SMAD4 or APC. Interestingly, mut were found in genes belonging to the proposed new cancer hallmark ‘epigenetic and RNA regulation’, such as BRD3, EPC1, PHF1 in almost every p included in our study. Regarding alterations that could be considered relevant for lung tumor pathogenesis/growth or as potential targets for treatment therapies, we were able to identify candidates in 4 of the 7 p. In one p, a case of a transmembrane domain ERBB2mut in exon 20 (p.E770delinsEAYVM) not previously detected by the OncoCarta v1.0 panel (that interrogates L755P, G776S/L/V/C, A775_G776insYVMA, P780_Y781insGSP, S779_P780insVGS mut) was found. In another p, three somatic mut in the BRCA1/2 genes were detected. Additionally, one p had an ALK point mut (p.P336K), for which no functional information is available, together with an APC mutation. In the remaining p, a non-hotspot mutation (although previously detected in a colorectal tumor) was found in CTNNB1. Conclusions: In this limited experience of whole-exome sequencing of a subgroup of stage IV lung ADC p, potentially targetable alterations not formerly detected by other techniques were found. We believe that genomic approaches to detecting alterations may be useful in clinical practice and will hopefully provide assistance in making treatment decisions.

generally preferred to continue the same systemic therapy after using SBRT for oligoprogressive and induced OMBC of initially polymetastatic disease irrespective of tumor subtypes, with the exception of SBRT for oligoprogressive triple-negative BC (TNBC) where the majority of respondents (55.8%) would change current therapy.Conclusions: Results of our survey showed discordance in the definition of OMBC. Even though a significant number of respondents would use SBRT for de novo OMBC, the vast majority preferred using SBRT after initial response to systemic therapy as compared to upfront SBRT. Respondents were more reluctant to use SBRT in TNBC compared with other tumor subtypes.Legal entity responsible for the study: Oncoalert Network.

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