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10594 Background: As germline testing in BC is becoming more accessible, a large body of evidence from distinct populations is revealing different prevalence of affected genes or recurrent and founder mutations. We evaluated a series of Brazilian BC patients from diverse regions of the country that were studied in a single laboratory facility for likely pathogenic/pathogenic variants (PV) and variants of unknown significance (VUS) in BRCA1/2 and other BC susceptibility genes (ATM, BARD1, CDH1, CHEK2, PALB2, RAD51C, RAD51D and TP53). Methods: We used multi-gene NGS panels covering from 35 to 105 genes, including copy number alterations, to perform sequencing in patients with diagnosis of BC from 2016 to 2021. With patient consent, we extracted clinical and pathological data from curated Real-World Database of Oncoclínicas Group to classify tumors according to hormone receptor (HR) and HER2 status and assess family history of cancer. Primary endpoint was prevalence of PV and VUS in BRCA1/2 and other breast cancer risk genes. Results: In total, 1,520 patients with BC were included in the analysis, 99% were female, median age at genetic testing was 46 years and 84% had family history of cancer. BC subtype was available in 717 cases (43% HR+/HER2-, 26% HER2+, 31% triple negative). Median age at genetic testing in HR+/HER2- population was 49 years and 44 years in HER2+ and triple-negative cases. Overall, 11.7% (CI95% 10.1-13.4) of the population had at least one PV in any BC risk gene: 50 in BRCA1, 49 in BRCA2, 22 in TP53 (17 had Brazilian founder p.R337H haplotype), 19 in PALB2, 18 in CHEK2, 15 in ATM, 7 in other genes (BARD1, CDH1, RAD51C, RAD51D) and 4 patients had co-existing PV in 2 BC risk genes. BRCA1/2 PVs were found in 7% of BC patients and BRCA1/2 VUS in 3%, being higher in triple-negative cases (11% PVs) than HR+/HER2- (5% PVs) and HER2+ (3%). For other BC risk genes, 5% of the patients had a PV, without differences according to BC subtype, and the prevalence of VUS was 14%. The prevalence of TP53 Brazilian founder mutation in BC was 1.2%. Median age of genetic testing was younger in population with BRCA1 PV (43 years) than BRCA2 PV (47 years) and other genes PV (46 years). Conclusions: In this real-world cohort of BC patients enriched for high-risk features such as young age at diagnosis, positive family history and triple-negative disease, the prevalence of BRCA1 and BRCA2 PV was very similar and represented only 56% of all PV detected. Different from other studies, TP53 mutations are the third most common germline alteration in the Brazilian population, with close to 80% of the cases presenting the founder mutation p.R337H. BC with epidemiologic high-risk features should be offered a germline test in Brazilian patients due to the considerable chance of a PV detection.

10559 Background: As a reaction to the COVID-19 pandemic, a nation-wide lockdown was enforced in Brazil in March 2020, cancer care was impacted, and cancer screening reduced. Therefore, an increase in cancer diagnoses at more advanced stages was expected. In this study, we extracted data from our nationwide real-world database to evaluate the impact of the COVID-19 pandemic on the stage at diagnosis of breast cancer (BC) cases. Methods: We explored curated electronic medical record data of female patients, over 18 years of age, diagnosed with BC and with established disease stage based on the AJCC 8th edition, who started treatment or follow-up in the Oncoclínicas (OC) between Jan 1, 2018, and Dec 31, 2021. The primary objective was to compare stage distribution at first visit during COVID-19 pandemic (2020-2021) with a historical control cohort from a period prior to the pandemic (2018-2019). We investigated stage distribution according to age at diagnosis and tumor ER/HER2 subtype in univariate models. Associations were considered significant if they had a minimum significance (P < 0.1 in Chi-square test). The historical numbers of patients with BC at OC make it possible to identify differences in the prevalence of stages in the order of 5% comparing pre and post pandemic periods with a statistical power greater than 80%. Results: We collected data for 11,752 patients with initial diagnosis of BC, with 6,492 patients belonging to the pandemic (2020-2021) and 5,260 patients to the pre-pandemic period (2018-2019). For both ER+/ HER2- and HER2+ tumors, there was a lower percentage of patients with early-stage (defined as stage I-II) in the years 2020-2021 vs 2018-2019 and a considerable increase in advanced-stage disease (defined as stage IV). For triple negative BC (TNBC), there was a significant higher percentage of patients with advanced-stage disease in the pandemic vs pre-pandemic period (table 1). Age over 50 years was associated with a greater risk of advanced stage at diagnosis after the onset of the pandemic, with an absolute increase of 7% (P two-sided <0.01) Conclusions: We observed a substantial increase in cases of advanced-stage BC in OC institutions as a result of delays in BC diagnoses due to the COVID-19 pandemic. The impact appeared greater in older adults, potentially because of stricter confinement in this group. [Table: see text]

e22539 Background: CHEK2 is one of the most commonly affected genes in different cancers. P/LP variants can display differences in phenotype and in penetrance in cancer families. Some of the most frequently described variants largely vary from population to population. CHEK2 variants are distributed in the whole gene sequence and it seems that some functional areas can be critical. Additionally, a significant number of variants detected in CHEK2 are classified as VUS and require appropriate functional testing for accurate classification. Therefore, we decided to contribute with databases presenting the largest cohort of CHEK2 P/LP and VUS detected through NGS panels in many cancer centers throughout Brazil. Methods: We conducted a retrospective cohort study including CHEK2 variant carriers identified by genetic testing ordered by Grupo Oncoclinicas health care professionals from 2017 to 2022. Primary endpoint was to describe the prevalence of CHEK2 P/LP and VUS and variants categories as well as sex at birth, age at diagnosis, phenotype and geographic distribution. Results: A total of 207 carriers of CHEK2 variants were identified, with 96 (46%) classified as P/LP and 111 (54%) as VUS. Majority of patients were female (88%), with median age at diagnosis of 45 years for those with P/LP variants. The most observed phenotype was breast cancer (125 cases, 60%), followed by prostate (11.5%), ovarian (7%), thyroid (2%) and kidney cancer (1%). Approximately 25% of patients either had a less common type of cancer, lacked a reported cancer diagnosis, or did not provide information regarding the specific type of cancer. The most frequent variants were p.Arg117Gly (14.5%) and p.Ile157Thr (7.2%). Despite being predominantly described in association with breast cancer in North American, c.1100del variant was the third most frequent in our population, occurring in 14 (6.7%) cases, with breast cancer being its slightly more common phenotype 57.1% (8/14 patients). Among p.Arg117Gly carriers, breast cancer was also the most frequently observed phenotype, accounting for 23 out of 30 patients (76.7%), whereas among p.Ile157Thr carriers, it represented a lower proportion of cases, 5 out of 15 patients (33.3%). Of the 207 patients, 58.4% were from the Southeast region and 25% were from the South region. Conclusions: This study is the largest cohort of germinative CHEK2 variants reported in Brazil, which showed p.Arg117Gly and p.Ile157Thr to be the most prevalent variants and breast cancer to be the most common phenotype, particularly among carriers of the p.Arg117Gly variant. The significant number of VUS identified, however, represents a challenge for genetic counseling in developing countries and highlights the need for further research to classify these variants as well as for functional testing to improve understanding about their association with cancer.