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Background: Comprehensive tumor analysis by Next Generation Sequencing (NGS) is imperative for targeted and immunotherapy related biomarkers’ analysis in metastatic breast cancer enabling personalization of cancer treatment in these patients. In parallel with targeted therapies, immunotherapies are also evolving, revolutionizing cancer therapy. Thus, biomarkers such as. Microsatellite Instability (MSI), and Tumor Mutational Burden (TMB) are commonly employed in NGS analysis due to their correlation to Immune Checkpoint inhibitors treatment.Methods: In the present study, tumor molecular profile analysis was performed in 73 metastatic breast cancer patients using a broad NGS assay, which analyzes more than 500 unique cancer related genes and is able to detect relevant single nucleotide variations (SNVs), indels, copy number variations (CNVs) and gene fusions, in addition to TMB and MS) simultaneously. Results: An actionable alteration was detected in 79.45% of the patients. 35.62% of them had at least one alteration with an on label treatment associated and 10.96% received information related to an off-label treatment (Tiers 1A.1 and 2C.1 respectively). Additionally, 31.51% of the tumors harbored an alteration that could be used for clinical trial inclusion (Table 1). The most prevalent altered gene in these patients was the PIK3CA gene, with 27.40% mutation rate. Moreover, in 11 cases (15.07%) the mutation detected was in a gene involved in the Homologous recombination (HR) pathway, with evidence of response to PARP inhibitors. BRCA1/2 genes were as expected the most prominent HR mutated genes (5 out of 11 HR mutations), while the remaining HR mutations involved other HR genes (ATM, BLM, CHEK2, FANCM, RAD50). 24.66% of the tumors had a TMB value >10muts/MB and thus were eligible for ICI treatment. The addition of TMB to targeted biomarkers’ analysis increased the number of patients with an on-label treatment recommendation by 8.22%. Conclusions: Tumor molecular profile analysis using NGS, in real world samples, is a first-tier method for metastatic breast cancer and provides important information for decision making in the treatment of such patients. Importantly, simultaneous analysis for targeted therapy and immunotherapy biomarkers could lead to better tumor characterization and offered actionable information in 9 out of 10 patients tested. However, appropriate interpretation of results from such analysis is essential for implementation in clinical practice and accurate refinement of the treatment strategy.. Table 1.Biomarker's summary in the 73 patients included in the studyPercentage of patients with Tier1 variantsPercentage of patients with 2C.1 variantsPercentage of patients with 2C.2/2D variantsPercentage of patients with Tier 3 variantsPercentage of patients with TMB>10muts/MBMEDIAN TMBPercentage of MSI-High patients35.62% (26/73)10.96% (8/73)12.33% (9/73)0% (0/73)24.66% (18/73)5.050% (0/73) Citation Format: Eirini Papadopoulou, Nikolaos Tsoulos, Vasiliki Metaxa-Mariatou, Aikaterini Tsantikidi, Georgios Kapetsis, Chrysiida Florou-Chatzigiannidou, Sonia Maravelaki, Evgenia Bourkoula, Dimitrios Fotiou, Georgios Tsaousis, Nikolaos Touroutoglou, Dimitrios Trafalis, Ioannis Boukovinas, Ioannis Varthalitis, Zacharenia Saridaki, Charalampos Zoublios, Eleni Galani, George Papatsibas, Christos Papadimitriou, Tania Zlatintsi, Polixenia Iorga, Bülent Orhan, Sualp Tansan, Tahsin Özatlı, George Nasioulas. Comprehensive tumor analysis by NGS in metastatic breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-01.

Summary Background: The impact of adjuvant chemotherapy (CT) in the management of resectable non-small cell lung cancer (NSCLC) is highly debated. The aim of the study was to evaluate the outcome of this category of patients, treated at the Military Hospital Bucharest (surgery) and Institute of Oncology Bucharest (CT). Patients and methods: We retrospectively analyzed the survival data according to various patients’ characteristics, the corresponding pattern of relapses, along with the data concerning the CT program. Results: A number of 311 consecutively treated patients (pts.), between January 1994 and October 2002, were evaluated. All patients were radically resected and received adjuvant CT. Chemotherapy was planned to be cisplatin-based and to be delivered for six cycles. In addition, 141 pts. (45%) received post-operative irradiation (RT). Demographics: sex, M 252 (81%)/F 59 (19%) and median age: 58 (range 31–75). Stage: I 55 (17%), II 71 (23%), III A 140 (45%) and III B 45 (15%). After a median follow-up of 46 months, the overall median survival (MS), considering all the patients, was 42 months and the 5-year survival rate (5-year SR) was 44%. According to stage, MS and 5-year SR were as follows: Stage I = not reached/94%; Stage II = 54 months/59%; Stage III A = 28 months/37% and Stage III B= 18 months/27%. According to lymph node status, the MS was not reached for pN-negative pts. and 26 months for pN-positive pts. ( P = 0.0002), while the 5-year SR was 75% versus 35%, respectively. Platinum-based CT was delivered in 295 pts. (95%). The medium number of cycles was five. A number of 86 (28%) relapses were recorded, of which 50 (16%) were distant, 25 (8%) local and 11 (4%) distant and local. The sites of the 50 distant relapses were BRA 24 (48%), OSS 10 (20%), PUL 6 (12%) and OTH 10 (20%). Conclusion: Our analysis shows good long-term survival data for adjuvant CT following surgery in NSCLC, which looks comparatively superior to those communicated for surgery-only series. Pathologic invasion of the lymph nodes has a strong adverse effect on patients’ outcome. The positive impact of CT in this setting is indirectly sustained by the pattern of relapses, which place the brain sanctuary on the first rank. Overall, the patients’ compliance was good and we delivered a medium of five cycles of adjuvant platinum-based CT.

The impact of adjuvant chemotherapy (CT) in the management of resectable non-small cell lung cancer (NSCLC) is highly debated. The aim of the study was to evaluate the outcome of this category of patients, treated at the Military Hospital Bucharest (surgery) and Institute of Oncology Bucharest (CT).We retrospectively analyzed the survival data according to various patients' characteristics, the corresponding pattern of relapses, along with the data concerning the CT program.A number of 311 consecutively treated patients (pts.), between January 1994 and October 2002, were evaluated. All patients were radically resected and received adjuvant CT. Chemotherapy was planned to be cisplatin-based and to be delivered for six cycles. In addition, 141 pts. (45%) received post-operative irradiation (RT). demographics: sex, M 252 (81%)/F 59 (19%) and median age: 58 (range 31-75). Stage: I 55 (17%), II 71 (23%), III A 140 (45%) and III B 45 (15%). After a median follow-up of 46 months, the overall median survival (MS), considering all the patients, was 42 months and the 5-year survival rate (5-year SR) was 44%. According to stage, MS and 5-year SR were as follows: Stage I = not reached/94%; Stage II = 54 months/59%; Stage III A = 28 months/37% and Stage III B= 18 months/27%. According to lymph node status, the MS was not reached for pN-negative pts. and 26 months for pN-positive pts. (P = 0.0002), while the 5-year SR was 75% versus 35%, respectively. Platinum-based CT was delivered in 295 pts. (95%). The medium number of cycles was five. A number of 86 (28%) relapses were recorded, of which 50 (16%) were distant, 25 (8%) local and 11 (4%) distant and local. The sites of the 50 distant relapses were BRA 24 (48%), OSS 10 (20%), PUL 6 (12%) and OTH 10 (20%).Our analysis shows good long-term survival data for adjuvant CT following surgery in NSCLC, which looks comparatively superior to those communicated for surgery-only series. Pathologic invasion of the lymph nodes has a strong adverse effect on patients' outcome. The positive impact of CT in this setting is indirectly sustained by the pattern of relapses, which place the brain sanctuary on the first rank. Overall, the patients' compliance was good and we delivered a medium of five cycles of adjuvant platinum-based CT.