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PURPOSE Young women with germline BRCA mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with BRCA mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations. PATIENTS AND METHODS This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline BRCA mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors. RESULTS Of 1,252 patients with germline BRCA mutations ( BRCA1, 811 patients; BRCA2, 430 patients; BRCA1/2, 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; P = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; P = .66) were observed between the pregnancy and nonpregnancy cohorts. CONCLUSION Pregnancy after breast cancer in patients with germline BRCA mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility.

78 Background: Colorectal cancer (CRC) is the third most common cancer in the world, and the second most frequent cause of death due to cancer. 5-10% of CRC cases are due to a hereditary predisposing syndrome, the most frequent being Lynch Syndrome (LS) followed by Familial Adenomatous Polyposis (FAP), characterized by loss of function of mismatch repair genes (MMR) and APC, respectively. The purpose of this study is to describe the spectrum of germline pathogenic variants among Mexican CRC patients using Next-generation sequencing (NGS). Methods: This study is original research approved by IRB; all patients signed the informed consent. 43 patients between 18-60 y/o with CRC were enrolled. NGS was performed using a panel which targeted a set of 94 genes and 284 SNPs known to play a role in cancer predisposing. Bioinformatics data analysis was carried out using Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) and an in-silico analysis to classify variants according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Mean age 48.71 y/o, 62.6% men. Germline pathogenic and likely pathogenic variants (PV/LP) were identified in 69% of sample. A molecular diagnosis of LS (MLH1, MSH2, MSH6, and PMS2) was confirmed in 12 (28%), and FAP in 5 (11.6%). It is remarkably the presence of 5 PV in PRF1 (2 G149S; 3 A91V), among other unusual genes for CRC. Also 12 double heterozygotes were identified, including one with PRF1 and CHEK2 PV. Conclusions: NGS allow the discover of new pathogenic variants that would not be suspected in classic hereditary syndromes. The understanding of other genes involved in other pathways could expand our understanding in the heritability of CRC. PRF1 emerges as a new candidate gene associated with CRC, previous evidence supports the role of PRF1 in solid tumors beside hematologic malignancies.

145 Background: Based on promising results from latest trials, a crucial point is to evaluate whether encorafenib (E) plus cetuximab (C), alone or in combination with chemotherapy, can improve clinical outcomes relative to current standard of care in previously untreated BRAFV600E mutant mCRC. Considering the high number of BRAFV600E mutant mCRC patients who will never receive a second-line treatment, the rationale of this strategy is to maximize treatment outcome within the first-line setting. Methods: We performed an in vivo study using human BRAFV600E CRC cell line-derived xenografts in nude mice. We evaluated the efficacy of encorafenib (E) + cetuximab (C), FOLFOX, and FOLFIRI, both as individual regimens and in combinations. Mice were treated for 3 weeks and followed for an additional 8 weeks to evaluate durability of tumor control. Additionally, we validated our findings using 3 BRAFV600E mutated patient derived xenografts. Tumors progressing on single agent and combined treatment were profiled by RNA sequencing, protein extraction for RPPA/Western blot, and establishment of in vitro primary cell cultures for further analyses. Results: Our study showed across all 4 models both FOLFOX and FOLFIRI, each in combination with encorafenib plus cetuximab, having greater efficacy than encorafenib plus cetuximab or either chemotherapy alone. No significant change in toxicity was seen with the addition of chemotherapy. Interestingly, in the one model with long term treatment, FOLFOX + E +/- C performed greatest over the long-term, with significant endpoint separation against all other treatment arms (P < 0.05). Conclusions: Taken together, results from our study suggest that the addition of chemotherapy to BRAF+EGFR targeted therapy can further increase the magnitude of response in BRAFV600E mCRC and is a promising combination now being explored clinically. Additionally, this research will substantially contribute to our understanding of the genetic and molecular bases of resistance to target therapies and chemo-based approach in BRAFV600Econtext.

22 Background: Inflammatory bowel disease (IBD) increases the risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) mortality is on the rise. It has been postulated that CA-CRC may be contributing to the increasing prevalence of early-onset CRC (EOCRC) but supportive studies are currently lacking. Molecular and clinical differences between CA-CRC and sporadic-CRC (S-CRC) have been reported, however outcomes for CA-CRC remains unclear. Signet ring cell carcinoma (SRC) is a rare subtype of CRC which is seen at higher frequencies, along with mucinous histology, in both CA-CRC and EOCRC. In this study, we validate the association of SRC and mucinous (SRC/M) histology with CA-CRC and EOCRC, and utilize it to estimate the amount of EOCRC attributable to undiagnosed or subclinical IBD. Methods: A retrospective study was conducted using three independent mCRC patient datasets from MDACC. The mATTACC discovery cohort consisted of 32 IBD- and 425 S-mCRC patients enrolled in a prospective biomarker trial. Validation of tumor histology was completed with a tumor registry (n=1696), excluding the MSI-High samples, and a real-world evidence (RWE) cohort from MDACC containing 269 CA-mCRC and 29,596 S-mCRC patients, was used as our validation cohort. Results: In the mATTACC cohort SRC/M histology was found in 37.5% of CA-mCRC and 11.7% of S-mCRC, showing a strong association between SRC/M and CA-mCRC (OR = 4.54, 95% CI: 2.19-9.43). The RWE cohort confirmed the correlation of SRC/M with CA-mCRC (28.6%) relative to S-mCRC (11.4%) patients (OR = 3.13, 95%CI: 2.39-4.09). An association was found between SRC/M and EOCRC (OR = 1.35; 95% CI: 1.24-1.47). By comparing the prevalence of SRC/M in EOCRC and late-onset CRC and correcting by the proportion of CA-CRC cases with SRC/M histology, we estimate that between 8.28% to 10.15% of EOCRC may attributable to undiagnosed/subclinical IBD. Using the RWE cohort, median overall survival was determined to be lower for CA-mCRC (31m) relative to S-mCRC (39m; p=0.007), yielding a HR of 1.26 (95% CI: 1.06-1.48). CA-mCRC patients with EOCRC (25m) were also found to have significantly worse outcomes than S-mCRC patients (40m) with EOCRC (p=0.0005; HR = 1.61, 95%CI: 1.23-2.11). Within CA-mCRC, patients with SRC or SRC/M histology (21m) had decreased OS compared to mucinous histology (51m), indicating the poor prognosis of SRC in CA-mCRC (p=0.028; HR=0.53, 95% CI: 0.3-0.94). Conclusions: Tumor biology consistent with CA-CRC, including SRC/M histology, may be present in 8.3% – 10.2% of patients with EOCRC without a clinical diagnosis of IBD, and harbors worse outcomes. Although other confounding biology may be underlying this association, recognition of undiagnosed IBD in CRC patients, especially those with metastatic disease, is important as it may impact prognosis and treatment strategies for this high-risk patient population.

e13536 Background: The COVID-19 Pandemic represents unprecedented new challenges for healthcare systems, care programs and especially for vulnerable populations like oncologic patients. The J&F Program, developed at the National Cancer Institute (INCan) in Mexico City, provides multidisciplinary care and navigation support for YWBC patients. During the first months of 2020, the whole mexican healthcare system, including the INCan and programs like J&F had to undergo structural adjustments to offer distance care attention (DCA) and face the Pandemic challenges. Methods: From March to September 2020, 196 patients received DCA (phone and video calls, text messages and virtual workshops), which addressed navigation, unmet psychological needs, psychoeducation, oncology and sexual support provided by different healthcare professionals (oncologists, psychologists, sexual specialists). Seventy agreed to participate in this study (intervention group, IG). Forty-three recently diagnosed breast cancer patients could not be contacted by the Program (control group, CG). The patients from the IG completed the emotional distress thermometer and were interviewed about stressors, coping strategies during the Pandemic, and satisfaction with the multidisciplinary support given by the J&F Program. We compared thestandard care given within the institutional facilities and the multidisciplinary support provided virtually by J&F Program for YWBC during the COVID-19 Pandemic regarding their perceived stressors and emotional distress. Results: The CG had more concerns about oncology treatments and their side effects (nausea p = 0.031, fever p = 0.007, anorexia p = 0.006) than the IG. Emotional distress was present in 77% and 86% in the IG and the CG respectively. The IG received significant navigation guidance and multidisciplinary support with the J&F Program’s DCA strategy during the Pandemic than the CG (p < 0.01 and p = 0.019). The J&F Program's psychological care significantly helped YWBC manage their distress (p = 0.001); 70% of the IG patients considered that the support given by the J&F Program dealt with the COVID-19 Pandemic challenges successfully (p < 0.01). Conclusions: DCA by theJ&F Program showed feasibility and benefit in the COVID-19 Pandemic context for YWBC. These findings suggest that multidisciplinary care could be preserved by combining care provision physically and virtually depending on patients' resources or unmet needs.

e12560 Background: Young women with breast cancer (YWBC) have worse survival outcomes compared to their older counterparts. Even though a higher recurrence rate has been previously documented in this population, there is still limited information regarding the timing, prevalence and type of disease recurrence. This study aims to describe the patterns of early recurrence in Mexican YWBC. Methods: Women aged ≤40 years at diagnosis, accrued in the Joven & Fuerte prospective cohort, with stage I-III BC and having at least a 2-year follow-up were analyzed. Recurrence-free survival (RFS) and overall survival (OS) at 2 years were evaluated using the Kaplan-Meier estimate. Log-rank and Fisher’s exact tests were employed for group comparisons; the Cox regression method was used to identify factors associated with RFS and OS. Results: A total of 210 patients with a median age at diagnosis of 36 years (range: 21-40) were analyzed. Most patients were diagnosed with stage II (50%) and III (39%). Distribution according to molecular subtype was: 50% HR+/HER2-, 26% TNBC, 17% HR+/HER2+, and 7% HR-/HER2+. In total, 31 (15%) patients experienced early disease recurrence. The two BC subtypes with the highest recurrence rate were TNBC (12/54; 22%) and HR+/HER2+ (6/35; 17%), followed by HR+/HER2- (12/106; 11%) and HR-/HER2+ (1/15; 7%). Stage at diagnosis was associated with a higher risk of recurrence (stage III: 21/82 (68%); stage II: 10/94 (32%); p= 0.003). Of the total recurrences, 23% were locorregional and the remaining 77% were distant metastases. The most common sites of distant metastases were lung (46%), bone (38%) and central nervous system (33%). Notably, 50% of distant recurrences affected multiple organs. Overall, RFS at 2 years was 85.2% (95%CI 79.7-89.4). In the univariate analysis, age ( < 35 v ≥35), type of surgery (conservative v mastectomy) and BMI ( < 25 v ≥25 kg/m²) were not significantly associated with RFS. In a multivariate model, node involvement (HR = 2.76; p= 0.044), not receiving chemotherapy (HR = 3.86; p= 0.024) and TNBC (HR = 2.47; p= 0.035) were independently associated with worse RFS. The OS found in this cohort was 92.9% (95%CI 88.4-95.6). In a multivariate model, TNBC (HR = 3.71; p= 0.029) and stage III at diagnosis (HR = 5.55; p= 0.008) were associated with worse OS. Conclusions: This cohort of YWBC experienced a low RFS at 2 years. As previously reported, patients with node involvement and TNBC faced a greater risk of early recurrence. Noteworthy, a high prevalence of distant metastases was observed, with half of them involving > 1 site. Future studies are warranted to elucidate the factors associated with early recurrence in YWBC. In addition, the incorporation of new treatment strategies is urgently needed to improve disease outcomes in this group.

e12624 Background: Obesity (BMI ≥30 kg/m2) and breast cancer (BC) are two major public health concerns worldwide. Obesity has been linked with aggressive clinicopathological features and inferior survival rates in patients with BC, regardless of molecular subtype. In addition, obesity has been associated with decreased pathological complete response (pCR) rates in some BC cohorts. However, the impact of obesity on pCR rates in different BC molecular subtypes is still a subject of debate. This study aims to explore the impact of obesity on pCR rates in women with different BC subtypes in a public health-care center. Methods: Medical records of women diagnosed with primary BC between 2009 and 2020 in a center in Monterrey, Mexico were reviewed. Patients with stage II or III at diagnosis treated with neoadjuvant chemotherapy (NAC) were considered eligible. Associations between variables were examined using Fisher's exact test of independence, employing logistic regression to calculate odds ratios (OR) when appropriate. Results: A total of 559 patients with a median age at diagnosis of 48 years (range 25-85) were included. Patients were diagnosed with stages II (37%) and III (63%). The most common molecular subtype was HR+/HER2- (49%), followed by TNBC (25%), HR-/HER2+ (15%), and HR+/HER2+ (11%). Regarding BMI, a significant proportion of patients was either overweight (34%) or obese (47%). In this cohort, a total of 134 (24%) patients achieved pCR following NAC with anthracycline- and/or taxane-containing regimens. pCR rates by subtype were as follows: HR-/HER2+ (41%), TNBC (34%), HR+/HER2+ (31%), and HR+/HER2- (13%). A significant association between pCR rates and molecular subtype was found (p

e13510 Background: The COVID-19 (COVID) pandemic presents many challenges to cancer patient treatment. Care coordination pathways are more complex to ensure safe screening and monitoring for COVID while reducing person-to-person interaction. The oncologic management of head and neck cancer (HNC) involves an interdisciplinary workflow. Time from diagnosis/specialized oncologic referral to initiation of treatment is critical for optimal outcomes. The insertion of any additional rate limiting factor could drastically increase the timeliness to care. Our study evaluates the effectiveness of patient navigation and the impact of institutional COVID process on timeliness to treatment. Methods: Operational workflow changes were set in place with goal of obtaining COVID testing prior to initiation of therapy. Patients with COVID symptoms after initial clearance were subjected to additional COVID testing. COVID screening was obtained in a single location when feasible. COVID positive or patients with pending results were triaged to determine risk/benefits of delaying treatment initiation and CDC guidelines for safe administration of therapy were considered. Patients with pending or positive results, but acute situation, were treated after hours in full PPE gear in order to reduce exposure risks. Results: Navigation information for 88 HNC patients were collected from 1/1/20 to 1/1/21. All patients were treated with curative intent. COVID testing data were collected contemporaneously with the pandemic from 4/1/20 to 1/31/21. Thirty patients with HNC required coordination of CMT and completed COVID screening test an average of 19 days prior to the start of therapy (29 negative; 1 positive). Two (6%) patients received their screening results after therapy initiation. Four patients did not complete therapy (13%); 26 completed (86%). Patients treated with radiation averaged 31 treatments (range 30-35) each treatment indicative of an aerosolized risk exposure. Each infusion representing and aerosolized and IV risk exposure. During the course of care we experienced zero patient-to-staff contracted COVID positives. Five staff members tested positive for COVID however contact tracing indicated outside source. Prior to the pandemic, average time from referral to appointment (TRA) with oncology specialist was 14.62 days, time from first appointment with oncology specialist to first treatment modality (TAT) was 46.29 days, and time from referral to our center and initiation of first treatment (TRT) was 60.91 days. During the pandemic, from March 2020 to May 2020, average TRA was 10.51 days, TAT was 24.09 days, and TRT was 34.6 days. Conclusions: Appropriate navigation, protocols and team vigilance resulted in improved timeliness to treatment. Continued delivery of oncologic care to HNC patients can be achieved without increased patient or staff risk for contraction of COVID.

e12622 Background: Immunologic biomarkers such as tumor infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) can provide prognostic information in breast cancer (BC) patients. Specifically, a high TILs level has been associated with pathologic complete response and enhanced disease-free survival (DFS). Furthermore, PD-L1 positivity has been associated with worse DFS and overall survival (OS). However, the interaction of both biomarkers as well as its association with survival outcomes in specific BC subtypes is still a subject of ongoing research. Methods: Medical records of women diagnosed with primary BC between 2013 and 2015 in a center in Monterrey, Mexico were reviewed. Eligible patients had at least 1 year of follow-up, stages I-III at diagnosis, and available tissue for TILs and PD-L1 assessment. PD-L1 positivity was defined as the presence of PD-L1 in ≥1% of tumor-infiltrating immune cells using the VENTANA SP142 assay. Classification of TILs into low ( < 30%) and high (≥30%) levels was performed for analytical purposes. Clinicopathological features were compared with Fisher’s exact tests and logistic regression models, as appropriate. The Kaplan-Meier method was used to calculate recurrence-free survival (RFS), and associations between variables were explored with log-rank or Cox regressions. Results: A total of 195 patients were included. Overall, 12.3% of BC biopsy specimens showed positivity to PD-L1 (8.3% [11/132] in HR+/HER2-, 5.9% [2/34] in HER2+, and 38% [11/29] in TNBC; p < 0.001). PD-L1 positivity was significantly associated with ER-negative status (OR 3.1; p = 0.013), high TILs (OR 5.7; p < 0.001), and high Ki67 expression (HR 12.5; p < 0.001). The median follow-up for the entire cohort was 61 months (95%CI 58-63). RFS in the PD-L1- group was significantly superior to the PD-L1+ group (85% vs. 66% at 5 years; p = 0.021). In a multivariate Cox model, PD-L1 positivity (HR 3.3), low TILs (HR 3.4), advanced stage (HR 2.8), and high histological grade (HR 2.5) were all independent prognostic factors for worse RFS. Based on these results, we further classified our cohort into four prognostic profiles based on PD-L1 and TILs status. The low TILs/PD-L1+ group experienced an inferior RFS than low TILs/PD-L1- patients (45% vs. 85% at 5-years; p-value < 0.001), while no difference was observed in the high TILs groups. Notably, when analyzing HR+/HER2- patients only, a similar statistical difference was observed between low TILs/PD-L1+ and low TILs/PD-L1- groups (HR 5.4, p = 0.009). Conclusions: In our cohort, PD-L1 positivity together with low TILs identified a subset of BC patients with a worse RFS. Interestingly, patients with HR+/HER2- BC fared worse in the low TILs/PD-L1+ subcategory than in the low TILs/PD-L1- group. Future studies are warranted to explore the prognostic value of categorizing patients based on TILs and PD-L1 status in different BC subtypes.

10562 Background: Breast cancer (BC) is the most common cause of cancer-related death and morbidity among young women in Latin America. This group has a higher prevalence of advanced disease stages at diagnosis compared to their older counterparts. Thus, strategies aimed at detecting BC at early stages are imperative. Breast self-examination (BSE) remains a useful strategy for BC detection, especially in women who do not routinely undergo screening with imaging studies. This study aims to evaluate factors related with BSE practice in Mexican young women with BC and assess its association with earlier disease stages. Methods: Women aged ≤40 newly diagnosed with BC from 2014 to 2020 at three cancer referral centers in Mexico accrued in the Joven & Fuerte cohort were included and asked to complete a socio-demographic survey. Fisher’s exact and Mann-Whitney U tests were used to evaluate associations between BSE and socio-demographic characteristics, as well as disease stages. Results: A total of 554 patients with a median age at diagnosis of 36 years (range: 19-40) were analyzed. Most patients (65%) were married or in a domestic partnership, and the majority were housewives (63%). Regarding educational background, 64% had completed at least high school, and up to 84% had a monthly income < 11,600 Mexican pesos (US$ 581). Overall, 85% of patients had public insurance, 6% had private insurance, and 9% were uninsured. The distribution of clinical stages at diagnosis was: 0 (2%), I (11%), II (45%), III (32%), and IV (10%). BC detection methods were: 85% by self/partner exam, 11% by an imaging study, and 4% by a healthcare professional. A total of 443 (80%) patients practiced BSE, of which 50% did it on a monthly basis, 18% every 2-3 months, and the remaining 12% every 4-12 months. Notably, a higher educational level (≥ high school v ≤ middle school) was positively associated with BSE practice (RR: 1.28; 95%CI 1.06-1.54; p= 0.005). No significant association was found between BSE and age (≤35 v > 35), marital status (in a relationship v no), occupation (housewive v other), monthly income ( < 11,600 v ≥11,600) or medical coverage (public/uninsured v private). Patients that performed BSE were more likely to be diagnosed with early BC (stages 0-II) compared to those that did not (61% v 45%; p= 0.003). No association was found between BSE frequency and stage at diagnosis. Noteworthy, patients with private insurance were more likely to be diagnosed with stages 0-II compared to those with public or no insurance (80% v 56%; p= 0.007). Conclusions: The significant association between BSE and earlier stages at diagnosis found in this study highlights the need to raise awareness and promote this practice among young women with the objective of downstaging BC diagnoses. Public health interventions such as educational and social media campaigns that aim to improve the correct practice of BSE might be particularly useful in settings with inadequate screening programs.

110 Background: BRAFV600E mutation identifies mCRC patients with poor prognosis with only little benefit from standard therapy. Analysis from TCGA revealed that 89% of BRAFV600E CRC tumors were associated with a high CpG island methylator phenotype (CIMP-H), which may result in epigenetic silencing of tumor suppressor genes, while only 29% of BRAF wild-type tumors are CIMP-H. In this study, we define key pathways regulated by global DNA hypermethylation in the context of BRAFV600E mutation. Methods: We analyzed the TCGA Illumina 450k array methylation datasets and RNA-sequencing datasets for 97 CIMP-H CRC tumors (27 BRAFV600E; 69 BRAF WT) identified by five universal CIMP annotations ( p14, p16, MLH1, MINT1, MINT2, MINT31). We defined differential methylation profile according to BRAF mutation status and calculated Spearman correlation between methylation and gene expression to identify CIMP-H BRAF-associated genes. Next, pathways enriched with CIMP-H BRAFV600E tumors were defined using PANTHER pathway analysis. Additionally, β-catenin IHC were conducted on 145 MD Anderson CRC patient samples and compared by CIMP and BRAF status. Results: BRAF mutation is associated with lower rates of APC mutation as has previously been shown (32%, 82%). We identified 6,097 differentially methylated probes by BRAF mutation status (FDR = 10-4), and as expected, our data suggests a higher methylation profile in BRAFV600E mutated tumors compared to BRAF WT. Intriguingly, CIMP-H BRAF-associated genes showed enrichment in the Wnt-signaling and cadherin signaling pathways ( p< 0.0001 (FDR < 0.0001)). Despite the epigenetic Wnt-signaling, nuclear β-catenin expression (as a measure of Wnt activity) in CIMP-H and BRAF tumors remains lower than for non-CIMP, and BRAF wild-type ( p= 0.0003 for comparison of CIMP). Conclusions: Genes under methylation regulation in the BRAF-mutant context showed enrichment in Wnt-signaling pathway. Since BRAFV600E CRC tumors have a low association with APC mutation, this data suggests role of epigenetic regulation of the Wnt-pathway activation. However, as measured by nuclear β-catenin, Wnt activation in these tumors is not as high as traditional APC-mutated CRC tumors. CIMP-H tumors with BRAFV600E mutation is a unique subset of CRC tumor that have Wnt-pathway activation regulated by epigenetic modifications more than a β-catenin activation.

e12652 Background: YWBC is associated with aggressive biology with a higher mortality rate and recurrence risk. Similar to older patients, pCR after NAC is a surrogate marker of disease-free survival and overall survival in YWBC. However, YWBC who did not achieve pCR did significantly worse. Metabolic profile (MP) has been used for biomarker discovery to monitor chemotherapy response. Few studies focus on using metabolomics to predict pCR in BC. The study aimed to identify MP in YWBC, before NAC to predict response to chemotherapy. Methods: A targeted metabolomics approach was employed to determine the concentration of 11 AAs, free carnitine, and 30 ACCs using electrospray tandem mass spectrometry in plasma of 30 YWBC patients, before NAC to select plasma biomarkers with the most predictive power to identify pCR in YWBC. Patients were classified in responders (R) and non-responders (NR), based on pCR or not-pCR reported by the pathologist department. The differences between R and NR groups were evaluated using an analysis of Random Forest decision trees according to the distribution of the variables. To evaluate the diagnostic power of each biomarker alone, we performed univariate receiver operating characteristics (ROC) analysis on each biomarker to obtain its ROC curve, ROC area under the curve (AUC), and standard error (SE) of the AUC. Results: We observed differences in MP between R and NR YWBC. Ten metabolites contributed most to differentiating between both groups. We developed a model that included two short-chain acyl-carnitines (AC4 and AC5:1) that allowed an AUC of 0.851 (0.767-0.921) and AUC of 0.737 (0.806-0.844) respectively, and ornithine with AUC of 0.723 (0.6-0.626). Conclusions: There are different MP among Mexican YWBC patients classified as R and NR to NAC. To our understanding, this is one of the first studies that evaluate MP in YWBC in Mexico. Further studies are needed to validate a metabolic signature to predict pCR in this patient group.

e12510 Background: Among premenopausal women with breast cancer (BC), adherence to endocrine therapy (ET) has often been reported suboptimal due to age-related adverse effects, lack of understandable information and inadequate social support. The current increased use of ovarian function suppression (OFS) may lead to even lower adherence rates in this group due to its high adverse effects profile. This study aims to assess the extent to which premenopausal patients comply with ET and to identify factors that hinder optimal adherence in Mexico. Methods: Women aged ≤50 years with primary stage I-III hormone receptor-positive BC receiving adjuvant ET for ≥1year were invited to fill a survey regarding their attitude towards ET and self-reported adherence. Fisher’s exact test was used to explore associations between categorical variables. This study was funded by AstraZeneca Mexico. Results: From Sep 2019 to Jan 2020, 127 patients with a median age of 45 years (range: 25-50) were included. Most had at least high school education (64%) and were unemployed (61%). ET distribution was: 69% tamoxifen (TMX) alone; 2% TMX switch to aromatase inhibitor (AI); 29% OFS plus TMX/AI. All patients recognized ET as a necessary part of their treatment and 97% believed it reduced their recurrence risk, yet 14% considered they had not received enough information about ET. Adverse effects were reported by 98%, predominantly hot flashes (82%), arthralgias (59%) and fatigue (58%). A statistically significant higher proportion of patients treated with a switch strategy or OFS experienced hot flashes, headache, insomnia, decreased libido and dyspareunia than those with TMX alone. Only 59% claimed their physician had taken measures to reduce these symptoms. Overall, 93% reported complete ET adherence. Nonetheless, 22% of them subsequently acknowledged missing 1-6 doses in the last month, the most common reasons being forgetfulness (78%), adverse effects (27%) and unwillingness to take the medication (11%). Unemployed patients were more likely to report daily compliance than students/employees (79% vs 60%; p = 0.02). No significant differences in adherence were found according to other factors, including type of ET. Conclusions: Premenopausal Mexican women self-report remarkably high rates of ET adherence. However, a considerable proportion misses ≥1 doses/month, with forgetfulness as the most common cause particularly in students/employees. Interventions aimed at reminding this group to take their ET and managing adverse effects could be crucial to improve adherence and, consequently, disease outcomes.

e12544 Background: Results from the Early Breast Cancer Trials Collaborative Group (EBCTCG) meta-analysis published in 2015 showed a significant reduction in risk of distant recurrence, bone recurrence and a 10-year breast cancer mortality reduction1. Moreover, Cancer Care Ontario and ASCO issued a guideline regarding the use of adjuvant bisphosphonates (AB) in breast cancer postmenopausal patients2. While these data are compelling, we have no information to support the implementation of this recommendation at Hospital San José’s Breast Cancer Center (HSJBCC). Methods: A retrospective analysis was performed to evaluate our compliance to the current recommendations for AB administration from 2015 through 2019. Inclusion criteria were based on the ASCO guidelines and comprised invasive breast cancer, postmenopausal status and early or locally advanced stage. Furthermore, in AB-treated patients we assessed the percentage of baseline calcium and creatinine measurement, prior dental evaluation, and concurrent calcium and vitamin-D supplementation during AB use. Results: A total of 106 patients met the inclusion criteria. Within the 4-year timeframe, AB was prescribed to 28/106 (26%) patients. Stratifying by year, we observed an increase of AB use rate from 4% in 2015 to 32% in 2019. Moreover, we observed a 93% baseline calcium and creatinine measurement, a 60% prior dental evaluation, and a 43% concurrent calcium and vitamin-D supplementation in the AB-treated population. Conclusions: HSJBCC recommendation for AB use is less than expected in the evaluated eligible patients in the 4-year timeframe. Despite an increase in our compliance to current ASCO guidelines it is not yet the standard of care at HSJBCC. Based on these results, we are currently planning a quality improvement initiative to undertake our low percentage of AB usage. [Table: see text]

e19064 Background: Alerta Rosa is a navigation program in Nuevo Leon, Mexico that aims to reduce delays in breast cancer (BC) diagnosis and treatment initiation irrespective of healthcare coverage. Via a call center, a navigator registers each patient’s initial concern and schedules a medical evaluation. This study aimed to assess the implementation of a triage system to guide appointment prioritization for undiagnosed BC patients with abnormal breast findings or imaging studies. Methods: Women that contacted Alerta Rosa were stratified according to their clinical characteristics into three priority groups. Asymptomatic women seeking check-up information were classified as low-priority (“Green”), those with nonspecific symptoms (e.g. mastalgia) or indeterminate image studies (BIRADS 0) as intermediate-priority (“Yellow”), and patients with suspicious symptoms (i.e. palpable mass, nipple retraction or bloody discharge), abnormal image studies (BIRADS 3-5) or an established BC diagnosis as high-priority (“Red”) for an appointment. The triage system’s ability to detect undiagnosed BC was evaluated against the number of patients per category in whom BC was later confirmed. Differences in time from initial contact to first medical evaluation were explored with an independent t-test. Results: From December 2017 to 2019, 561 women with a median age of 44 years (range: 8-89) contacted Alerta Rosa. 369 (66%) reported breast symptoms, 92 (16%) sought check-up information, 68 (12%) had an indeterminate/abnormal image study and 32 (6%) had received a BC diagnosis and wanted a second opinion. Accordingly, 16% of patients were classified as “Green”, 25% “Yellow” and 59% “Red”. The median time from stratification to medical evaluation was 4 days for the “Red” group and 7 days for those in other categories ( p= 0.003). A total of 558 appointments were scheduled, of which 441 (79%) were attended. Excluding those who had received a prior BC diagnosis, 20/299 patients from the “Red” group had BC confirmed (6.7%) compared to 1/138 patient from the “Yellow” (0.7%) and none from the “Green” categories. Therefore, the “Red” category achieved a sensitivity of 95.2% (CI95%: 76.2-99.9%) and specificity of 53.8% (CI95%: 49.3-58.3%) for BC. Conclusions: The triage system adequately identified women with different probabilities of having BC. Thus, the implementation of a stratification system could help identify high risk patients in limited-resource settings where screening programs are ineffective and efforts to prioritize access to medical attention is crucial to achieve early-stage diagnoses.

59 Background: Ensuring quality of care in our breast cancer center (BCC) at Hospital Zambrano Hellion in Monterrey, Mexico has been one of the main objectives since its commencement in 2016. To achieve this goal, we evaluated our compliance to ASCO’s Quality Oncology Practice Initiative (QOPI) 84 breast cancer related metrics as a part of a quality improvement (QI) project undertaken during the 2018 Quality Training Program (QTP) in Alexandria, VA. Methods: We established a multidisciplinary QI team engaged in data acquisition, process improvement and implementation in our BCC. We developed a Microsoft Word medical record template and established a new “first time visit” model to achieve our objective of 80% documentation rate of 13 identified reasonably achievable QOPI metrics. Monthly Plan-Do-Study-Act cycles were conducted for 6 months from August through December 2018. Results: After a sample data abstraction of 20 patients’ medical records, our baseline QOPI-compliance resulted in 40/84 QOPI metrics being met by our BCC program. The remaining 44/84 were distributed in two categories, the first 13/44 were labeled as “done/not documented” metrics, and the second set of 31/44 metrics were labeled as “not done/not documented” metrics given they were not performed at all. We approached the 13/44 “done/not documented” metrics for this project based on our priority matrix. After our QI intervention, we surpassed our objective by the third PDSA cycle. Furthermore, by March 2019 we reached 95% cumulative compliance of those metrics. Conclusions: The development of a systematic QI approach enhanced our BCC QOPI-compliance in 13 reasonably achievable metrics to 95% over a 6-month period. Currently, we are targeting the remaining 40/84 metrics to ultimately adhere to all breast cancer QOPI standards. To our knowledge, we are the first Mexican BCC pursuing a QOPI-compliant practice through ASCO’s QTP initiative.

e17008 Background: Mexico is the sixth country with the highest number of diabetics, this being the second cause of death. Between 8-18% of cancer patients have Diabetes (DM) as comorbidity. Studies have reported DM has worst prognosis in Overall Survival (OS) and Progression Free Survival (PFS) in patients with Cervical Cancer (CC). Aim: to compare OS in patients (pt) with a diagnosis of CC and DM, and to evaluate this outcome in relation to the clinical stage and the glycemic level at diagnosis of CC. Methods: data was obtained from pt treated for invasive CC between 2006 and 2016. Pt aged ≥20 years, with squamous, adenocarcinoma or adenosquamous histology. 59 pt with CC and DM in group 1 (G1), and 118 pt with CC without DM in group 2 (G2), paired 1:2 according to clinical stage, age and comorbidities. Results: Prevalence of DM in pt with CC was 16%. Follow-up of 142.2 months (median of 40.4 months), lower OS for G1 was seen (74.6% vs 77.1%), without statistical significance (p.803). PFS was similar for both groups (67.8% G1 vs 66.9% G2, p .608). In patients with locally advanced and metastatic disease, a lower OS and PFS were found in G1, without statistical significance. 42.4% diabetic pt had glycemic level < 130 mg / dL). OS was lower in pt with higher glycemic level (70.6% vs 80%), not being statistically significant (p .32). PFS was similar in both groups (G1: 68% vs G2: 67.6%, p.852). Analysis for influence of metformin treatment, evidenced a higher OS among pt receiving metformin (84.8% vs 61.5%), without statistical significance (p 0.65). PFS was higher in the metformin group (78.8 vs 53.8%), with a trend towards statistical significance (p .052). Conclusions: Pt diagnosed with CC and DM do not have different OS compared to those without DM. There was a tendency towards the improvement of PFS in pt with CC and DM, who received metformin.

10517 Background: Despite the growing complexity in the healthcare sector, physicians rarely receive formal training in leadership skills. In a previous survey, Citaku et el identified a set of leadership competencies (LC) which were evaluated by North-American (NA) and European (EU) leaders involved with medical education. We aim 1) To apply this same survey to a population of Latin-American (LA) physicians from the oncology community and related areas who hold leadership positions of various levels; 2) To compare the results with those of the previous survey and 3) To perform subgroup analyses within the LA cohort. Methods: The survey was sent to close to 8.000 members of contributing medical societies from LA countries. In addition to the 63 questions with 5 possible responses, we also collected data on type of institution (private vs public), country of practice, main specialty, gender, age, years of experience in oncology and years of experience in leadership position. Results: We collected a total of 217 responses on a web-based tool. LA leaders placed the highest value on task-management competencies(91,37% of `important` or `very important` responses vs 87,0% for NA/EU; p < .0001), followed by self-management(87,45% vs 87,55%; p = NS), social responsibility(86,83% vs 87,48% ; p = NS), innovation(86,69% vs 85,31% ; p = NS) and leading others(83,31% vs 84,71% ; p = NS). Social responsibility, which was first in importance in the NA/EU survey, was only third in the LA survey. Subgroup analyses revealed significant interactions which will be fully presented. Conclusions: We successfully applied the survey to a population of LA medical leaders from the oncology community and related areas. LC valued by LA leaders somewhat differ from those valued by their NA/EU counterparts, implying that cultural aspects might influence the perception of desired/required LC. We also detected significant variations in the responses within the LA population. Our data might indicate that current physician leadership training programs should be tailored to suit specific needs and cultural aspects of each region. Further validation of this survey in other clusters of world culture is warranted.

1090 Background: Among patients with metastatic breast cancer (MBC), there is paucity of data regarding knowledge and understanding about disease stage and goals of treatment. The limited evidence shows that up to 40% of MBC patients ignore their stage and reports inadequate educational resources and support. Aim: To assess MBC patients’ knowledge of their disease and satisfaction with the medical information received. Methods: 185 patients diagnosed with MBC who attended follow-up medical appointments at INCan from June to December 2018 were asked to complete a survey to assess their knowledge on MBC curability, subtype, topics reviewed with the oncologist, need of additional information regarding MBC and satisfaction with the quality of the information they received. Clinical data was obtained from the medical records. Descriptive statistics were applied, and the association between qualitative and quantitative variables was assessed with the Chi square test and the Mann Whitney U test, respectively. This study was supported by the SPARC mBC Challenge. Results: Only 52% of patients knew that their disease is not curable, while 31% were not sure and 17% thought it was curable. 82% ignored their MBC subtype and 81% reported to want more information about their cancer. 64% scored their satisfaction with the provided information ≥9 (out of 10), and 74% stated that their most helpful source of information was the medical staff. A statistically significant association was found between the perception of the impossibility of curing MBC and better patient satisfaction (p = 0.038). Likewise, better patients’ satisfaction was associated with older age (p = 0.002), longer time since initial diagnosis (p = 0.018) and since diagnosis of MBC (p = 0.014). Conclusions: Our results dramatically illustrate the lack of understanding patients have regarding their cancer, even when reporting high satisfaction with the received information, and identify a critical need for improvement of healthcare providers’ communication skills. Directed efforts should be implemented to enhance patients’ comprehension to promote their participation in decision-making processes, adherence and, ultimately, outcomes.

e18387 Background: The subcutaneous presentation of trastuzumab has been recently incorporated into the treatment regimen of HER2-positive breast cancer (BC). Its use has been associated with cost savings and reduced chair time, being especially suitable for public health systems. Aim: To estimate the cost savings of the use of SC-T compared to intravenous trastuzumab (IV-T) according to patient weight, and calculate the infusion time of SC-T in a tertiary healthcare facility at TecSalud from Feb 2018 - Jan 2019. Methods: From a total of 2068 oncological treatments, 756 corresponded to SC-T, either alone or concomitantly with chemotherapy (CT). For cost estimation, we considered $1,103 USD per SC-T vial, $1,162 USD per IV-T vial and $2.6 USD per mg of IV-T, as per governmental rates. We compared the actual treatment cost of 600 mg fixed SC-T dose with the hypothetical cost of administering IV-T at a dose of 6 mg/kg, considering its price per vial and per mg. The total time of SC-T infusion was reported. Results: Median patient weight for the 756 reported SC-T treatments was 72 kg (45 - 127 kg). Of these, 561 consisted of SC-T alone; and 56% had adjuvant, 34% neoadjuvant and 10% palliative intent. The estimated cost of the 756 doses of SC-T was $833,500 USD. Considering patients’ weight, 46% of the infusion treatments would have required 2 IV-T vials, with a total of 1105 vials and an absolute cost of $1,282,374 USD. Likewise, if cost per mg of IV-T is examined, we would have used 338,744 mg of IV-T, with an estimated cost of $894,284 USD. Approximate savings of SC-T use would reach $448,874 USD per vial payment and $60,784 USD per mg payment. The median time of SC-T only infusion was of 3 minutes (1 - 20 minutes); and no adverse effects were documented during its administration. Conclusions: The SC-T fixed dose (irrespectively of patients’ weight) results in significant practical and financial advantages as weight-adjusted dosing is not required. This is specially relevant in countries like Mexico, where > 70% of BC patients are overweight/obese, requiring higher doses of IV-T and resulting in greater expenses. Thus, the use of SC-T not only offers greater convenience to patients, but also reduces overall healthcare costs compared to standard IV infusion.

e23190 Background: Communication in oncology practice presents numerous challenges. Patients may react to the diagnosis and treatment information with unpredictable and difficult to manage emotions, which may distress clinicians and affect patient-physician relationships. An effective communication has shown a beneficial effect on satisfaction from both patients and providers, as well as on quality of health care provision and patients’ adherence, decision-making processes and outcomes. Aim: To identify the most important and hardest topics to discuss during consultation that pose a challenge for Mexican medical oncologists during their clinical practice. Methods: Physicians were reached out by a messaging platform to complete a survey that addressed the most relevant and difficult issues for discussion and the frequent challenges they face during information exchange. Results: A total of 115 oncologists completed the survey. Most of them identified treatment objectives, prognosis and treatment selection as important issues to discuss with patients. They coincided that the hardest matters to disclose were palliative care referral, treatment objectives, prognosis and recurrence. Also, oncologists reported that the most important challenges they face when communicating with patients are being honest without being hopeless (43%) and responding to patients’ emotions (21%). 92% expressed that they would like to receive formal training in communication skills. Conclusions: The issues regarded as highly important to discuss with patients were also the most difficult ones to address, possibly due to barriers related to patients’ emotional reactions when receiving bad news. The incorporation of a psychologist could promote calmness and trust, aid in information assimilation, and provide support to partners and relatives, as needed. Also, results showed the interest of oncologists in receiving formal training in communication skills, which reinforces the need to include this training as part of the medical oncology curriculum to ease transmission and comprehension of information. [Table: see text]

1584 Background: Hospital-based studies have reported a 15% prevalence of BRCA1/ BRCA2( BRCA) mutations, with a slightly higher yield of other predisposition genes on multigene panel testing (MGPT) among women with EOC, and National Comprehensive Cancer Network guidelines recommend genetic cancer risk assessment for women with EOC. However, there is limited data about the genetic epidemiology of EOC among underrepresented populations, such as Hispanics. Consequently, we determined the germline mutation profile of Hispanics with EOC, and compared them with non-Hispanics. Methods: We included all women with a personal history of EOC from the U.S. and Latin America (LatAm; Mexico, Colombia, and Peru), enrolled in the Clinical Cancer Genomics Community Research Network registry. We assessed the prevalence of pathogenic variants (PV) in BRCA1/ BRCA2( BRCA) and other genes, contrasting the germline mutation profile between Hispanics living in LatAm, U.S. Hispanics, women of Ashkenazi Jewish (AJ) ancestry in the US, and other U.S. non-Hispanics. Results: Among 1186 women with EOC (209 from LatAm, 254 U.S. Hispanics l, 78 AJ, and 645 other non-Hispanic), 262 (22%) had a PV in BRCAgenes. Hispanics from LatAm and the U.S. had a similar frequency of BRCAmutations to AJ (30.6%, 29.9%, and 38.4%, respectively; p = 0.14); while non-Hispanics showed a significantly lower frequency of BRCAmutations (14.2%, p = 0.03). The most frequently mutated gene was BRCA1(n = 197, 74.6%), followed by BRCA2(n = 67, 25.3%). Among BRCA-negative cases (n = 924), 59% (n = 545) were evaluated by MGPT and PVs were identified in 2.9% [6 Hispanics (1.2%), 3 AJ (3.8%) and 26 Non-Hispanics (4%)]), of which 66% (n = 23) were in mismatch repair genes ( MSH2, MLH1, MSH6, PMS2), and 34% (n = 12) in other EOC-associated genes ( BRIP1, NBN, PALB2, RAD51C, and RAD51D). Clinically actionable PVs in ATM (n = 4; 0.3% ) and CHEK2 (n = 6; 0.5% ) were also observed. Conclusions: Hispanics with EOC have an elevated frequency of PV, similar to that of classic founder populations such as AJ, and significantly higher than other non-Hispanics. This is partially explained by a high prevalence of recurrent LatAm-specific PV, highlighting the importance of conducting genetic studies in underrepresented populations. There was modest incremental benefit of MGPT.