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Background Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. Methods This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. Results A total of 135 patients were included. Median age at diagnosis was 53 years old (19–84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0–1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka‐Koga system, overall survival (OS) at five‐years was 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1–7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3–12.7]; p = 0.016) were significantly associated with increased risk of death. Conclusions Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control., Here, we report the largest analysis of clinical characteristics of thymomas and outcomes in Latin American patients. Out of 135 patients included in the study, 21.5% (n = 29) concurrently presented myasthenia gravis. Relapse‐free survival rates at five‐years were 58.5% for stage I–II, and 35.4% for stage III. Five‐year overall survival rates were 73.4%, 63.8% and 51%, at stages I–II, III–IVA and IVB, respectively.

PURPOSE Major progress has occurred in multiple myeloma (MM) treatment in recent years, but this is not seen in low- and middle-income countries. MATERIALS AND METHODS We retrospectively assessed the efficacy and safety of cyclophosphamide, thalidomide, and dexamethasone (cyclophosphamide 400 mg/m2 for 5 days, thalidomide 100 mg once daily, if tolerated, and dexamethasone 40 mg once weekly; in 28-day cycles) in patients with newly diagnosed MM treated at our institution between April 2008 and December 2012. Survival outcomes were estimated by the Kaplan-Meier method. RESULTS Fifty-nine patients were found to meet the selection criteria. Median age was 56 years (27-78). Fifty-nine percent (n = 35) were male. International Staging System three was found in 24%. The median number of treatment cycles was 11 (range 4-12). After a median of 81-month follow-up (range 5-138 months), the overall response rate was 69.5%. The complete response and very good partial response were 5% and 32%, respectively. Median progression-free survival (PFS) was 35 months (95% CI, 18 to 41). The 3-year PFS was 47.4% (95% CI, 34.5 to 59.6) and 5-year PFS was 24.9% (95% CI, 14.4 to 36.9). The median of overall survival (OS) was 81 months (95% CI, 33 to not reached). The 3-year OS was 63.4% (95% CI, 49.2 to 74.6), and 5-year OS was 57.5% (95% CI, 43.2 to 69.4). The most common adverse event was neutropenia (grade 3 and 4, 30.5%). Out of 23 patients eligible for stem-cell transplantation, 10 (43.5%) proceeded with autologous transplantation. Treatment-related deaths occurred in four patients (6.7%). CONCLUSION Cyclophosphamide, thalidomide, and dexamethasone achieves good response rates with tolerable toxicity, especially in patients age 65 years or younger representing a feasible approach for patients with MM in low-income health care settings.

Background To assess the correlation of WHO histological classification and Masaoka-Koga staging system of thymic epithelial tumors (TETs) with prognosis. Methods We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka-Koga staging system. Survival curves were constructed with Kaplan-Meir method. Results There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was high (65%). With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka-Koga staging had an effect on survival. Conclusions The results indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment. Key points SIGNIFICANT FINDINGS OF THE STUDY: The WHO histological classification, the Masaoka-Koga system and surgery treatment were associated with overall survival. What this study adds To determine prognosis factors in TETs.

Adjuvant chemotherapy decreases the recurrence risk and improves survival rates; however, it is unclear whether a delayed initiation is associated with adverse outcomes, especially in triple negative breast cancer (TNBC). In this study, we evaluated the influence of the time to start adjuvant chemotherapy (TTC) in the outcomes of TNBC.We retrospectively analyzed 15 years of data from patients with TNBC who received adjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru). TTC was categorized into 4 groups: ≤ 30, 31 to 60, 61 to 90, and ≥ 91 days. We evaluated overall survival (OS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were used to identify prognostic factors.In total, 687 patients were included. The mean age at diagnosis was 49.1 years (SD, 11.8 years), and most (62.6%) patients had pathologic stage T2. The median TTC was 48.1 days (SD, 27.4 days); 189 (27.5%) received chemotherapy ≤ 30 days; 329 (47.9%), between 31 and 60 days; 115 (16.7%), between 61 and 90 days; and 54 (7.9%) in ≥ 90 days. In the multivariate analysis, a TTC between 31 and 60 days (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.17-2.72), 61 and 90 days (HR, 2.38; 95%CI, 1.43-3.97), and ≥ 91 days (HR, 2.45; 95% CI, 1.32-4.55) was associated with an increased mortality in contrast with a TTC 30 days. Although a TTC between 31 and 60 days, 61 and 90 days, and ≥ 91 days was associated with an increased risk of DRFS (HR, 1.86; 95% CI, 1.24-2.79; HR, 2.34, 95% CI, 1.42-3.867; and HR, 3.16; 95% CI, 1.78-5.61, respectively).A delaying in TTC ≥ 30 days was associated with poorer outcomes. Our data suggest that several efforts should be conducted to avoid a delayed TTC in patients with TNBC.

Peru is a South American nation with a growing and aging population of 31 million people with a life expectancy at birth of 76.7 years. The country is divided into 25 regions, 79% of the population is urban, and Lima, the capital, concentrates more than a third of the population.1 Although Peru is an upper-middle-income country, health expenditure represents only 5.1% of the gross domestic product, which is lower than the average of Latin America and the Caribbean (LATAM) (8.56%).2 Out-of-pocket health expenditure is 30.9%.3 Peru has a comprehensive National Cancer Plan and two population-based cancer registries in Lima and Arequipa. Revisión por pares

Background: The gene expression profiling assay OncotypeDx (ODx) prognosticates the risk of estrogen receptor positive (ER+) breast cancer (BC) recurrence and assesses the likely benefit from adjuvant chemotherapy in addition to endocrine therapy. There have been several attempts to develop algorithms that provide similar outcome prediction to the ODx assay with the use of routine clinicopathological characteristics. These models appear to predict high-risk ODx RS but are unable to reliably rule out the presence of patients with intermediate-risk disease. Our objective was to identify the clinicopathological factors associated with intermediate and high-risk categories. Methods: We retrospectively reviewed the electronic medical records of patients with early-stage ER+ BC for whom ODx recurrence score (RS) was available. Patients were diagnosed and treated at 3 specialized cancer centers between 2010 and 2017. Two multinomial logistic regression models (crude and adjusted) were constructed to assess the association between clinicopathological characteristics and ODx RS as a categorical variable. The adjusted model included the following variables: ODx RS, age, tumor size, node status, grade, lymphovascular invasion and hormonal receptors. The reported association measure was the relative prevalence ratio (RPR) with its respective 95%CI. Results: A total of 551 patients were included. Patients had a mean age of 56.2 ± 11.9 (SD) (range: 26-89). 9.6% (n=53) of patients were≤40 years old.The size of the tumors ranged from 0.1 cm to 7.2 cm (median = 1.5 cm; IQR 1.0-2.2cm). A minority of patients had lymph node involvement (5.8%, n=32). By subtype, carcinomas were mostly ductal (83.5%, n=460), followed by lobular (10.0%, n=55) and mucinous (3.5%, n=19). The majority of tumor exhibited an intermediate histological grade (71.6%, n=386). Ki 67 was available in 58.8% patients (n= 324), with a median Ki67 of 20 (IQR 10-30). In the adjusted multinomial logistic regression model, factors associated with ODx intermediate-risk category were grade 3 (RPR=4.78; 95%CI: 2.01-11.39) and having either ER or PR Conclusion: Grade 3, ER o PR Citation Format: Ruiz R, Morante Z, Namuche F, Urrunaga D, Leon M, Ziegler G, Aguilar A, Chavez Mac Gregor M, Gomez H. Clinicopathological characteristics associated with intermediate and high-risk ODx RS [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-18.

Background: The gene expression profiling assay OncotypeDx (ODx) prognosticates the risk of estrogen receptor positive (ER+) breast cancer (BC) recurrence and assesses the likely benefit from adjuvant chemotherapy in addition to endocrine therapy. Numerous clinical utility studies have shown that acknowledging the RS impacts on clinical decision making, leading to a decrease in chemotherapy (CT) use. However, the cost of the assay limits it widespread use, especially in low and middle-income countries. Our objective was to determine the patterns of use of ODx, its results and the subsequent treatment choices in a large Latin American cohort. Methods: We retrospectively reviewed the electronic medical records of patients with early-stage ER+ BC for whom ODx recurrence score (RS) was available. Patients were diagnosed and treated at 3 specialized Peruvian cancer centers between 2007 and 2017. Descriptive results for numeric variables were presented as means with standard deviation (SD) or medians with interquartile range (IQR), depending on their distributions; otherwise, we expressed the qualitative variables as numbers with percentages. We evaluated the association between ODx RS category and treatment using the Chi-squared test. Results: A total of 551 patients were included. Patients had a mean age of 56.2 ± 11.9 (SD) (range: 26-89). 9.6% (n=53) of patients were ≤40 years old. The size of the tumors ranged from 0.1 cm to 7.2 cm (median = 1.5 cm; IQR 1.0-2.2cm). 36 (6.5%) patients had tumors ≤ 0.5cm and 7 (1%) had tumors > 5cm. A minority of patients had lymph node involvement (5.8%, n=32). ODx was ordered in 55 cases (10%) of lobular carcinoma and in 23 cases (4%) of favorable histology tumors (19 mucinous, 4 tubular). Most tumors exhibited an intermediate histological grade (71.6%, n=386). Ki67 was available in 58.8% patients (n= 324), with a median Ki67 of 20 (IQR 10-30). Using commercial cutoffs RS was distributed as follows: low (0–17) = 316 (57.4%), intermediate (18–30) = 177 (32.1%), and high (≥31) = 58 (10.5%). In general, 57.5% (n=317) of patients received endocrine therapy (ET) as their only systemic treatment and 42.5% (n=234), also received CT (ET + CT). In the low-risk category, 87.3% (n=276) of patients received ET and 12.7% (n=40), ET + CT. Within the intermediate-risk category, most patients received ET + CT (77.4%, n=137). Only one patient in the high-risk category did not receive CT. There was a significant association between the RS group and treatment choice (p Impact of ODx RS results on treatment recommendations Oncotype risk categories LowIntermediateHighp valueTreatmentn%n%n% Conclusion: ODx significantly influenced treatment decisions in our cohort, however an overutilization of CT was found in low-risk patients. Further data analysis is needed to explain the higher than expected use of CT. Also, there is room for improvement in the selection of cases that undergo ODx testing. Citation Format: Ruiz R, Morante Z, Namuche F, Urrunaga D, Aguilar A, Schwarz J, Leon M, Ziegler G, Chavez Mac Gregor M, Gomez H. Evaluation of Oncotype DX testing and subsequent treatment choices in the Latin American setting [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-17.

Background: Adjuvant chemotherapy decreases the risk of recurrence and improves survival rates but it is unclear whether a delayed initiation is associated with adverse outcomes. Information available is especially scarce for triple negative breast cancer (TNBC) which represents a high-risk group. We evaluated the influence of time to chemotherapy (TTC) on TNBC patient's survival outcomes. Methods: We retrospectively analyzed the data using the medical records of TNBC patients who received adjuvant chemotherapy at Instituto Nacional de Enfermedades Neoplasicas between 2000-2014. TTC was defined as the number of days between surgery and the first dose of chemotherapy. Patients were categorized into 4 groups according to TTC: ≤30, 31-60, 61-90, ≥91 days. We evaluated recurrence-free survival (RFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used. Results: 687 patients were included. Mean age at diagnosis was 49.15 (range, 21-89) and most patients were stage II (60.1%) or III (29.45%). They received either anthracyclines or anthracyclines and taxane-based chemotherapy (96.1%). Median TTC was 41 days. 189 (27.5%) received chemotherapy at or before 30 days; 329 (47.9%), between 31 and 60 days; 115 (16.7%), between 61 and 90 days and; 54 (7.9%) beyond 90 days. Median follow-up was 101 months. 10y-DFS was 81.4%, 68.6%, 70.8% and 68.1% among patients who received chemotherapy ≤30, 31-60, 61-90, ≥91 days, respectively (p=0.005). Accordingly, 10y-OS was 82%, 67.4%, 67.1% and 65.1% among patients who received chemotherapy ≤30, 31-60, 61-90, ≥91 days, respectively (p=0.003). In the multivariate analysis, TTC was an independent prognostic factor for RFS and OS. Patients with TTC of 31-60 days (HR, 1.92; 95% CI, 1.225 to 2.998), 61-90 days (HR, 2.38; 95% CI, 1.354 to 4.172) and ≥91days (HR, 2.47; 95% CI, 1.250 to 4.886); had worse survival compared with those who initiated treatment in the first 30 days after surgery. Patients with TTC of 31-60 days (HR, 1.94; 95% CI, 1.243 to 3.034), 61-90 days (HR, 2.45; 95% CI, 1.402 to 4.265) and ≥91days (HR, 2.79; 95% CI, 1.418 to 5.506); had worse survival compared with those who initiated treatment in the first 30 days after surgery. Conclusion: Delayed initiation of adjuvant chemotherapy in TNBC patients over 30 days is associated with a decrease in RFS and OS rates. The greater the delay, the worse the outcomes. As this represents a feasible opportunity for improvement, every attempt should be made to avoid delayed adjuvant chemotherapy initiation in this high-risk group of patients. Citation Format: Morante Z, Ruiz R, De la Cruz - Ku G, Namuche F, Mantilla R, Lujan MG, Fuentes H, Schwarz J, Aguilar A, Neciosup S, Gomez H. Impact of the delayed initiation of adjuvant chemotherapy in the outcomes of triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS2-05.

Background The 21-gene recurrence score (RS) predicts the benefit of adjuvant chemotherapy (CT) in ER-positive HER2-negative breast cancer (BC) and has been validated in population where women under 40 are underrepresented.Young BC pts are more likely to receive adjuvant chemotherapy (CT) in addition to endocrine therapy (ET). Our objective was to assess the RS results in young (≤40 yo) vs older (>40 yo) pts and evaluate the impact of age on clinical decision-making according to RS categories. Methods We retrospectively reviewed electronic medical files of all patients with early stage hormone receptor BC for whom RS was available between 2007 and 2017 in 3 specialized cancer centers. We used the Mann-Whitney and Chi-squared tests to assess differences between age group. Similarly, we evaluated the association between age groups and treatment, within each ODx category. To determine if age was associated with CT use in the low risk category, a logistic regression model was constructed. Results A total of 551 pts were included, 53 (9.6%) ≤40 yo and 498 (90.4%) >40 yo. No statistical differences were found between the younger and older groups in T (p=0.874), N (p=0.794), stage (p=0.188), or grade (p=0.791). Young patients underwent radical surgery more frequently than their older counterparts (41.5 vs 25.7%, p=0.014). Statistically significant differences were also observed in ER mean, which was lower in the younger group (80 vs 90%, p40 years received CT (p=0.037). Conclusions Our results indicate that RS tends to be higher in patients with BC ≤ 40 yo and that the frequency of high-risk RS is significantly higher in the younger group, suggesting biological differences between groups. 28% of young patients with low-risk RS from our cohort are overtreated. Based on these results, it should be considered to develop a test adjusted to the age of the patients. Citation Format: Ruiz R, Namuche F, Morante Z, Aguilar A, Urrunaga D, Ziegler G, Chavez Mac Gregor M, Leon M, Gomez H. Age's importance in early breast cancer: Oncotype Dx results in patients ≤40 years [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-16.

Background The gene expression profiling assay OncotypeDx (ODx) prognosticates the risk of estrogen receptor positive (ER+) breast cancer (BC) recurrence and assesses the likely benefit from adjuvant chemotherapy in addition to endocrine therapy. There have been several attempts to develop algorithms that provide similar outcome prediction to the ODx assay with the use of routine clinicopathological characteristics. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use. Methods We retrospectively reviewed the electronic medical records of 330 patients with early stage ER+ BC for whom ODx recurrence score (RS) was available. Patients were diagnosed and treated at two specialized cancer centers between 2014 and 2017. Our objective was to determine the ki67's median differences between ODx risk groups. We used Spearman rho for the correlation between Ki67 and ODx score and used Kruskal-Wallis test for compare medians, pairwaise comparison for the intergroup relations. Results Mean age at diagnosis was 57.42 years (range 28-89). Mean tumor diameter was 15.67 mm. 78.9% were intermediate histologic grade and 9.7% patients had lymph node involvement. Median expression of ER and PR were 90% (5-100) and 70% (0-100), respectively. We assessed the correlation between Ki67 and ODx score, with a pearson r:0.31, p Median Ki67 was 20 (1-100). According to ODX RS, 61.5% of tumors were low risk, 30.3% were intermediate risk and, 8.2% were high risk. Median Ki67 within each category group is as follows: low: 15 (IQR:15), intermediate: 20 (IQR:18) and high: 40 (IQR:35), with a statistically significant difference between medians (p Conclusions The data showed directly proportional trend between Ki67 and ODx score. In our population there is a statistically significant difference between Ki67 medians according to ODx risk groups. Citation Format: Namuche F, Ruiz R, Morante Z, Aguilar A, Gomez H. Oncotype Dx recurrence score risk groups according to Ki67, a predictor to be considered [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-22.

Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, its cost makes it prohibitive for many health care systems. Our objective was to develop a model that uses routine clinical and pathological parameters to identify ODX high risk patients which require adjuvant chemotherapy. Methods: We retrospectively reviewed ODX and pathology reports from 190 early BC patients treated between 2014 and 2016 in a specialized cancer center. Our population was divided into a training (n:133) and validation set (n:57). In the training set, among available clinico-pathological variables (age, T, ER, PR, Ki67, Elston-Ellis grade) a multiple linear regression model was carried out to select those significantly associated with ODX. Coefficients of statistically significant variables were used to build an equation. The equation was applied in the training set. These results were confronted to ODX categories. The best threshold for selecting high risk patients was identified in the training set and tested in the validation set. Results: Among the tested variables, tumor size (pT), progesterone receptor (PR), Ki67 and Ellston-Ellis grade were significantly associated with ODX RS (Table 1). The linear predictor is: (0.2544 x pT) – (0.0739 x PR) + (0.0861 x Ki67) + (5.4232 x Elston grade). The threshold score for this equation was set on 14 to discriminate high from low-intermediate risk patients. The test was able to correctly classify high risk patients with a sensitivity of 78%, a specificity of 72% and a negative predictive value of 98%. Conclusion: With further refinement ODX could be omitted in patients classified as high risk by our predictor therefore restricting and optimizing the use of ODX to a smaller population of patients. The observed ODX distribution in our patients is similar to previously reported series suggesting that this equation could be informative in similar clinical settings. Additional external testing using new datasets is ongoing. Citation Format: Ruiz R, Namuche F, Flores C, Aguilar A, Gomez HL. Optimizing the use of oncotype Dx in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-12.

Background: The gene expression profiling assay OncotypeDx (ODX) predicts the likelihood of estrogen receptor (ER) positive breast cancer (BC) recurrence and assesses the likely benefit from both hormonal therapy and chemotherapy. Many clinical scores that estimate the risk category of ODX are being tested. Ki67 is frequently incorporated into these assessments, although there is no standard cut-off for its use. Methods: We retrospectively reviewed the electronic medical records of 190 patients with early stage ER+ BC for whom ODX recurrence score (RS) was available. Patients were diagnosed and treated at a specialized cancer center between 2014 and 2016. Our objective was to find out the degree to which an optimal ki67 cut-off correlates with ODX risk category. We also aim to determine an association between classical clinicopathological variables (St. Gallen (SG) 2015) could predict ODX risk category. Chi square test was used. Results: The characteristics of patients according to ODX risk category are shown in Table 2. Mean age at diagnosis was 59 years (range 28-89). Mean tumor diameter was 15mm, 84.2% were intermediate grade and 4.7% patients had lymph node involvement. Mean expression of ER, PR and Ki67 were 87%, 53% and 22%, respectively. According to ODX 62.1% patients were low risk, 30.5% were intermediate risk and 7.4% were high risk. An overall concordance of 46.8% (73/190) was found between SG 2015 and the risk category of ODX (75.7% for low, 33.3% for intermediate and 23.9% for high RS). When changing SG Ki67 cutoffs to ≤20% (for low Ki67) and ≥30% (for high Ki67), an overall concordance of 56.3% (107/190) was found (69.6% for low, 47.3% for intermediate and 23.9% for high RS) and this was statistically significant (p=0.00) (Table 3). Conclusion: In our population there is no a direct correlation between classical clinicopathological variables and ODX score. Despite being a specialized center, the utility of classical clinicopathological variables for predicting ODX risk category is limited. Citation Format: Namuche F, Ruiz R, Flores C, Gomez HL, Aguilar A. Ki67 cut offs and oncotype DX recurrence score in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-11.

Triple negative breast cancer (TNBC) accounts for 15%-20% of all breast cancer, and is still defined as what it is not. Currently, TNBC is the only type of breast cancer for which there are no approved targeted therapies and maximum tolerated dose chemotherapy with taxanes and anthracycline-containing regimens is still the standard of care in both the neoadjuvant and adjuvant settings. In the last years, metronomic chemotherapy (MC) is being explored as an alternative to improve outcomes in TNBC. In the neoadjuvant setting, purely metronomic and hybrid approaches have been developed with the objective of increasing complete pathologic response (pCR) and prolonging disease free survival. These regimens proved to be very effective achieving pCR rates between 47%-60%, but at the cost of great toxicity. In the adjuvant setting, MC is used to intensify adjuvant chemotherapy and, more promisingly, as maintenance therapy for high-risk patients, especially those with no pCR after neoadjuvant chemotherapy. Considering the dismal prognosis of TNBC, any strategy that potentially improves outcomes, specially being the oral agents broadly available and inexpensive, should be considered and certainly warrants further exploration. Finally, the benefit of MC needs to be validated in properly designed clinical trials were the selection of the population is the key.

The interactions between pregnancy and breast cancer (BC) are complex. Overall, parity is associated with long-term protective effects against BC, however in a small group of susceptible patients, pregnancy can lead to the development of a form of BC with a particularly poor prognosis. Pregnancy-associated breast cancer (PABC) remains an under-studied but important and growing clinical problem worldwide. Several aspects of PABC, including risk factors and mechanisms involved in its occurrence and aggressiveness, are incompletely understood. This review aims to summarize the epidemiology, biology, patho-physiology and clinical characteristics of PABC. We emphasize that age at first pregnancy, absence of breastfeeding and family history stand out as possible risk factors for developing PABC that ought to be incorporated into clinical tools for assessing a woman's risk of developing PABC. Also, improved methods for identifying women at risk of developing PABC in the general population are needed.

Cancer has become a global pandemic with disproportionately higher mortality rates in low- and middle- income countries, where a large fraction of patients present in advanced stages and in need of end-of-life care. Globally, the number of adults needing end-of-life care is greater than 19 million, and up to 78% of these patients are living in low- and middle- income countries. In the Americas alone, more than one million people are in need of end-of-life care, placing an enormous burden on local health systems, which are often unprepared to meet the challenge presented by this complex patient population. In Latin America, cancer care is characterized by the presence of vast inequalities between and within countries, and the provision of end-of-life care is no exception. Disparities in access to advanced care planning, with a lack of provision of adequate palliative care and pain medication, are common in the region. These shortcomings are related in large part to inadequate or inappropriate legislation, lack of comprehensive national palliative care plans, insufficient infrastructure, lack of opportunities for clinical training, unreliable reporting of data, and cultural barriers. This report reviews the current status of end-of-life care in Latin America, focusing on identifying existing deficiencies and providing a framework for improvement.

Median age at diagnosis of lung cancer is 70 years. Its presentation in patients 40 or younger is uncommon and it has been proposed that maybe it is a different disease due to its clinical characteristics and genetic makeup. There are a limited number of studies in this population and they report different clinic-pathological characteristics in comparison with older patients. We described the incidence of lung cancer patients diagnosed at age 40 or younger at the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima-Peru; from 2009 to 2017 and evaluated the characteristic of NSCLC. Epidemiologic and clinic-pathological data was collected from clinical files. Analysis was carried out using SPSSvs19 software. We identified 3823 patients with lung cancer seen at INEN during the study period. Among these, 166 (4.3%) patients were 40 years or younger, and 137/166 (82.5%) were NSCLC. Median age at diagnosis was 36 years (range 14–40 years) and 59.1% of patients were female. A smoking history was present in 14.4% of patients. Frequent symptoms at diagnosis were cough (62.0%), chest pain (51.8%) and dyspnea (40.9%). Adenocarcinoma was the most common histological type (63.3%). Most patients had advanced disease at diagnosis (84.7%). The median overall survival was 8.2 months. The proportion of young patients with lung cancer in our population is higher than that reported in the most recent literature. Lung cancer in the young is mostly sporadic, more frequent in women, usually adenocarcinoma type and it presents with advanced disease, resulting in a very poor survival.

e12562 Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, it puts aside important clinical features. Our objective is to develop a model that uses routine clinical parameters associated with Oncotype Dx score to estimate the recurrence rate in our population. Methods: We retrospectively reviewed ODX and pathology reports from 371 early BC patients diagnosticated between 2014 and 2016 in a specialized cancer center, with a 5 year follow up. Variables were selected first with a univariate cox regression, then the statistically significant variables underwent a multivariate cox regression. The β coefficients from selected variables were used to create the prediction formula. Results: Among the tested variables, ki67, estrogen receptor (ER) and ODx score were significantly associated with Recurrence. The linear predictor is: (0.1331 x Ki67) + (0.4232 x ER)+(0.2112xODx score). The threshold score for this equation was set on 33 (median value) to discriminate low and high estimated risks for recurrence. The correct classification rate (CCR) for the training and validation sets was 76% and 68%, respectively. Conclusions: It is possible to optimize the Oncotype Dx to better determine a recurrence score with selected pathological features.

e12579 Background: Triple negative breast cancer (TNBC) seems to be associated with a hereditary disease cause based on the earlier age of onset, the high rate of TNBC cases with a positive family history of cancer, and the higher prevalence of breast cancer susceptibility genes. The impact of family history in breast and/or ovarian cancer (FHBOC) in TNBC overall survival is unclear, we conducted this study to evaluate this factor in a Peruvian cohort. Methods: Retrospectively reviewed the medical files from TNBC patients diagnosed at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, from 2000 to 2014. New cases with histologically confirmed TNBC defined as lack of expression of estrogen and progesterone receptors by immunohistochemistry and HER2- were included. A positive FHBOC was defined as a history of breast and/or ovarian cancer in 1st, 2nd and/or 3rd degree relatives at any age. Patients who had three affected relatives in two generations with two of them being first-degree relatives were considered as exhibiting a clinical autosomal dominant (AD) inheritance pattern. Results: 2006 patients, 99.8% were females. Mean age was 50.2 years old (19 - 95) and 54.6% were postmenopausal. According clinical staging: stage I, 7.2%; stage II, 34.2%; stage III, 51.0%; and stage IV, 6.5%. 76.5% of women underwent surgery. 13% (n=266) had a positive FHBOC. Of these, 44.0% (n=117), 35.0% (n=93), and 13.5% (n=36) had 1st, 2nd, and 3rd degree affected relatives, respectively. An AD inheritance pattern was observed in 20.7% (n=55) of patients with FHBOC. With a median follow-up of 80 months (range 0 - 249), 5y-overall survival (OS) for the whole population was 53.8%. 5 year-OS was significantly better in patients with FHBOC as compared to those without it; 64.5% vs. 52.2%, respectively (HR 0.73; 95% CI [0.60-0.88] p=0.001). FHBOC showed a positive impact on survival rates among patients with stages III and IV (5-year OS 42.3% vs. 32.7%; HR 0.79; 95% CI [0.64-0.99], p=0.041) but not in stages I and II (5-year OS 88.4% vs. 81.3%; HR 0.72; 95% CI [0.49-1.08], p=0.11). The 5y-OS for the patients with an AD inheritance pattern was 70.9%. However, pairwise multiple comparison did not find a significant difference between these patients and those with FHBOC without an AD inheritance pattern (62.8%). On multivariate analysis, FHBOC (HR: 0.80; 95% CI [0.66-0.97], p=0.023), had an independent effect on OS, adjusted for age, menopausal status, clinical stage and surgery. Conclusions: A positive FHBOC was associated with an improved survival in patients with TNBC, suggesting FHBOC as an independent prognostic factor. These results need validation and confirmation through additional retrospective cohorts and analysis in prospective clinical trials.

Background: The Global Cancer Institute (GCI) breast cancer multi-disciplinary tumor boards (MTBs) are live, online telemedicine discussions of breast cancer patient case scenarios between breast cancer specialists in low- and middle-income countries (LMICs) and expert breast cancer specialists in the United States (US). In the US MTBs are routinely held in most cancer centers and have been shown to improve patient outcomes and patient and family quality of life. GCI launched breast cancer MTBs in 2012 with the goals to improve breast cancer patient care in underserved populations globally, to establish an online platform to allow live communication and collaboration among oncologists, and to serve as an educational tool for oncologists. Methods: During our MTBs case scenarios are presented by global oncologists for discussion and input by a panel of both community/tertiary care expert breast oncologists from our global network. During each MTB, three cancer centers present challenging breast cancer patient scenarios. Patient scenarios are presented in English, according to a standard PowerPoint template. After presentation guideline - or clinical trial-based discussions are held for each case. As the patient cases originate from oncologists in LMICs, optimal and best locally available clinical care in rural and remote settings are discussed. For educational purposes the MTBs and the associated YouTube panel discussions are archived online and can subsequently be viewed by practicing oncologists and trainees globally. Links to relevant international guidelines, published and ongoing clinical trials, and other educational resources are also provided to all MTB attendees. Results: Since its initiation in 2012, the GCI MTBs have engaged a network of 370 oncologists in LMICs and 20 expert panelists from nine cancer centers in the United States. Together the oncologists in LMICs represent 28 tertiary cancer centers and 116 community oncologists in 19 countries across Latin America, Eastern Europe, Asia, and Africa. Conclusions: GCI breast cancer MTBs are a powerful educational and networking tool for oncologists in LMICs to improve their patterns of clinical practice, conduct multi-disciplinary discussions and access research collaborations. GCI invites oncologists throughout Latin America, Europe, Asia, and Africa to join our tumor boards and further expansion of its MTB network. GCI currently surveys oncologists in our network before and after attendance of MTBs to measure modifications in oncologists' practice and adherence to international clinical practice guidelines. Citation Format: St. Louis J, Bukowski A, Paulino E, Ferreyra ME, Nunes J, Mejia G, Duarte C, Ruiz R, Touya D, Polo S, Chavarri-Guerra Y, Moreno J, Georgieva N, Tsolko T, Obayedullah Baki M, Luna HC, Goss PE. Global Cancer Institute online tumor boards to improve global patterns of clinical practice for breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-17-03.

e19258 Background: Immunotherapy has changed the landscape of cancer treatment. The aim of this work was to describe the adverse events related to immunotherapy treatment in diverse type of malignant tumors using real-world data. Methods: This is a retrospective review of patients with diverse type of advanced malignancies treated with immunotherapy at Oncosalud-AUNA (Lima-Peru) during the period 2016-2018. We present a descriptive analysis of the clinicopathological and treatment features of the patients, as well as data of safety of immunotherapeutic agents. Results: In total, 37 patients were included in the study. The median age was 67 years (38 to 84 years); 64.9% of patients were male; 54.1% were smoker/former smoker and 45.9% non-smokers. Regarding to the primary tumor, 75.7% were lung cancers (82.1%, adenocarcinomas and 17.9%, squamous cell carcinomas), 16.2% were melanomas, 5.4, head and neck cancers and 2.7%, were bladder cancers. Central nervous system metastases were present in 29.7% of patients. Immunotherapy was given after a first line in 43.2% of cases, 40.5% after the second line and 16.2%, after the third line of treatment. The types of immunotherapy were prembrolizumab in 54.1%, nivolumab in 40.5%, atezolizumab in 2.7% and avelumab in 2.7%. 27% of cases had combination of immuno with chemotherapy. Finally, regarding to adverse events, 94.6% had any adverse event; 48.6% fatigue and asthenia; 35.1%, nausea; 32.4, pruritus/rash; 27.7%, decreased appetite; 18.9%, hypo/hyperthyroidism; 13.5%, diarrhea/colitis; 10.8%, pneumonitis and 5.4%, infusion-related reactions. Conclusions: During the study period we had a slightly higher incidence of adverse events than reported by other works. It could be probably due to the age of patients and several prior lines of treatment.

e13101 Background: Lung cancer epidemiology and survival data is lacking in LA. This information is relevant for understanding regional cancer burden and for designing targeted interventions for cancer control. Methods: Retrospective analysis of lung cancer cases diagnosed at Instituto Nacional de Enfermedades Neoplasicas (INEN) from 2010 to 2014. Data was manually curated from clinical files. Results: 1384 patients were included. Median age at diagnosis was 64 years old (range 20-92) and 51.6% were females. The histologic type was adenocarcinoma, NOS carcinoma, squamous cell carcinoma and small-cell carcinoma in 72.3%, 12.8%, 9.4% and 3.5% of the cases, respectively. The adenocarcinoma/squamous cell carcinoma ratio was 7.7. Among NSCLC cases, most patients presented with advanced disease. Stage III (9.2%) and IV (85.5%) were the most frequent. With a median follow-up of 71.5 months, median overall survival (OS) was 9.2, 7.7 and 8.1 months for adenocarcinoma, NOS carcinoma and squamous carcinoma, respectively. Five-year OS for stage III was 6% and for stage 4, 4%. Detailed results are shown in the table. Conclusions: The epidemiological profile of lung cancer in Peruvian patients is different from that of other countries with a younger age at diagnosis, a preponderance of females over males and an unexpectedly high frequency of adenocarcinomas. This may be in concordance with the low prevalence of tobacco smoking and the high prevalence of EGFR mutations reported for our population as well as with particular exogenous exposures such as biomass fumes from inhouse cooking. The molecular characterization of this cohort of patients is ongoing. [Table: see text]

e18109 Background: The main immunotherapy (IMMUNO) trials that led to the approval of these agents for non-small cell lung cancer (NSCLC) accrued a minimum number of Hispanic (HISP) patients (pts) or, in some studies, no HISP pts at all. Additional data is thus needed to validate outcomes in HISP pts with NSCLC treated with IMMUNO. While it is known that genomic profiles and cancer survivals are different between HISP, Non-Hispanic Whites (NHW), and African-Americans; no study has yet looked at differences in IMMUNO outcomes between these populations. Methods: We present data in 436 NSCLC pts treated with IMMUNO at 5 large institutions (3 in the US, 2 in Latin America). The agents evaluated include: nivolumab, pembrolizumab and atezolizumab. 256 pts were HISP and 180 pts were NHW. Most of the pts were treated with single agent therapy as second line (or beyond) while a small group of pts were treated as first line. The primary endpoints of the study were: response rate (ORR), progression free survival (PFS) and overall survival (OS). Results: Among NHW pts, disease control rate (DCR) was 67% for Adenocarcinomas (Adeno) and 46% for squamous cell carcinomas (SQCC). In HISP pts there were no differences in DCR rates between both histologies: 68% for Adeno and 67% SQCC. There were no statistical significant differences among HISP and NHW pts regarding ORR, PFS, OS, and responses according to PD-L1 status. Conclusions: This is the largest publication and comparison of NSCLC immunotherapy outcomes in HISP vs NHW pts. No significant differences were found in the clinical outcomes between these 2 ethnic groups despite expected genomic differences. Pts with actionable mutations were excluded as they usually do not get IMMUNO as first or second line; an approach that might change after IMPOWER 150. These results are comparable to the ones seen in Checkmate and Keynote studies. As expected, higher response rates were seen in first line therapy and pts with PD-L1 (+) status. Further comparisons will be better addressed by a larger prospective study.[Table: see text]

Objetivos. Determinar las características clínicas, histológicas y los factores pronósticos del cáncer cervical (CC) en pacientes jóvenes peruanas. Materiales y métodos. Análisis retrospectivo de pacientes de 35 años de edad o menos diagnosticadas con CC entre el 2008 y el 2012 en el Instituto Nacional de Enfermedades Neoplásicas. Resultados. 449 pacientes tenían neoplasias epiteliales. Los tipos histológicos principales fueron: carcinoma de células escamosas (84,9%), adenocarcinoma (11,0%) y carcinoma adenoescamoso (2,4%). El tamaño tumoral promedio fue 4,98 cm. También se identificó anemia (55,7%), creatinina elevada (21,2%) e hidronefrosis (13,8%). El 82,3% de los pacientes presentaron enfermedad localmente avanzada. Los estadios IIB (47,4%) y IIIB (25,8%) fueron los más comunes. La supervivencia global a 5 años fue de 59,5% (I, 90,9%; II, 57,5%; III, 42,7% y IV, 13,3%). La creatinina elevada, la anemia, el tamaño tumoral, el compromiso parametrial y la hidronefrosis fueron factores que afectaron la supervivencia. No se encontró relación significativa entre el tipo histológico y la supervivencia. La presencia de anemia (Hazard Ratio ajustado [HRa]: 2,5; intervalo de confianza al 95% [IC 95%]: 1,6-4,0) y la hidronefrosis (HRa: 1,6; IC 95%: 1,0-4,0) estuvieron independientemente asociados con la supervivencia; asimismo, el compromiso parametrial con (HRa: 3,3; IC 95%: 1,57,2) o sin (HRa: 2,6; IC 95%: 1,3-5,3) extensión al hueso pélvico. Conclusiones. El cáncer cervical en jóvenes peruanas es diagnosticado en estadios avanzados. La supervivencia global en cada estadio es similar a la reportada en pacientes mayores. Se confirmó la importancia de los factores convencionales relacionados con el pronóstico. La anemia fue un factor de pronóstico independiente importante que requiere mayores investigaciones. Objective. To determine the clinical and histological characteristics and prognostic factors of cervical cancer (CC) in young Peruvian patients. Materials and methods. Retrospective analysis of patients younger than 35 years old diagnosed with CC between 2008 and 2012 in the Instituto Nacional de Enfermedades Neoplásicas. Results. 449 patients had epithelial neoplasms. The main histological types were: squamous cell carcinoma (84.9%), adenocarcinoma (11.0%) and adenosquamous carcinoma (2.4%). The average tumor size was 4.98 cm. Anemia (55.7%), elevated creatinine (21.2%) and hydronephrosis (13.8%) were also identified. 82.3% of the patients presented locally advanced disease. Stages IIB (47.4%) and IIIB (25.8%) were the most common. Overall 5-year survival was 59.5% (I, 90.9%; II, 57.5%; III, 42.7% and IV, 13.3%). Elevated creatinine, anemia, tumor size, parametrial involvement and hydronephrosis were factors that affected survival. No significant relation was found between histological type and survival. The presence of anemia (adjusted hazard ratio [aHR]: 2.5; 95% confidence interval [CI 95%]: 1.6-4.0) and hydronephrosis (aHR: 1.6; CI 95%: 1.0-4.0) were independently associated with survival; likewise, the parametrial commitment with (aHR: 3.3; CI 95%: 1.5-7.2) or without (aRH: 2.6; CI 95%: 1.3-5.3) extension to the pelvic bone. Conclusions. Cervical cancer in young Peruvians is diagnosed in advanced stages. Overall survival in each stage is similar to the reported in older patients. The importance of conventional prognosisrelated factors was confirmed. Anemia was an important independent prognostic factor requiring further investigations.

The HER2 receptor as measured by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) is overexpressed in 15-20% of all breast cancers and traditionally represents adverse biology and a guarded prognosis, particularly in HER2 positive metastatic breast cancer (MBC). Trastuzumab and newer anti-HER2 targeting agents have significantly improved the clinical outcomes of patients with HER2 positive MBC. The development of new techniques has led to discovery of promising biomarkers that can lead to more precise selection of patients for anti-HER2 therapies. This paper summarizes these new biomarkers, useful in selecting patients for treatment with new and emerging therapies for HER2 positive MBC. Emerging next generation sequencing techniques have truly changed the landscape of HER2 positive MBC. Deployment of multiple anti-HER2 therapies in combination is a strategy which has yielded additive or even synergistic effects and has led to markedly improved patient outcomes in HER2+ MBC. In the future, in order to further improve the treatment of these patients and to reduce toxicities, we need to improve our understanding of HER2-dependent pathways and their function, and to develop further treatment combinations while optimizing selection of patients by identifying new biomarkers. The results of prospective studies using CTCs, cDNA and other promising new biomarkers are awaited with great interest.

Aim An in silico pathway analysis was performed in an attempt to identify new biomarkers for cervical carcinoma. Methods Three publicly available Affymetrix gene expression data sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total 9 cervical cancer cell lines, 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples. An Agilent data set (GSE7410; 5 normal cervical samples, 35 samples from invasive cervical cancer) was selected as a validation set. Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. We compared the lists of differentially expressed genes between normal and CIN3 samples on the one hand (n=1923) and between CIN3 and invasive cancer samples on the other hand (n=628). Results Seven probe sets were identified that were significantly overexpressed (at least 2 fold increase expression level, and false discovery rate

e16553 Background: Neoadjuvant chemotherapy with Carboplatin and Paclitaxel every 3 weeks show higher rates in optimal debulking surgery compared with those primarily operated. We explored Carboplatin and Paclitaxel dose-dense as neoadjuvant treatment for advanced ovarian carcinoma. Methods: Patients with primarily unresectable epithelial ovarian cancer was treated with carboplatin (AUC 6) day 1 plus paclitaxel 80 mg/m2 every week, Days 1-8-15 every 21 days for three cycles follow by interval cytoreduction and adjuvant chemotherapy for three more cycles. The main objective was rate of optimal cytoreduction and secondary objectives: pathologic response rate, time to progression, progression-free survival (PFS), overall survival (OS) and toxicity profile. Results: Between Jan-2011 and Dec-2013, 39 patients received neoadjuvant treatment, median age: 58 years (47-73), status performance, ECOG 1: 24 (61.5%). EC III-C/IV = 26/13. High grade serous adenocarcinoma 26 (66.7%), unspecified serous 10 (25.6%), Mucin...

e12538 Background: Breast Cancer (BC) is a heterogeneous disease. Mammograpy images of BC has been associated with tumor features. We evaluated relationship between radiologic features of pre-neoadjuvant chemotherapy (NAC) lesions and clinico pathological tumor features. Methods: We evaluated mammography films and clinicopathological information of BC patient who received NAC followed by tumor resection at Instituto Nacional de Enfermedades Neoplásicas from 2000 to 2011. Results: 495 BC cases were selected. Most cases were staged in clinical Tumor size stage 4 (48.2%) and node stage 1 (58.7%); and had a GIII histological grade (51.2%). Breast density (BD) was classified as BIRADS grade 1 in 17%, grade 2 in 22%, grade 3 in 35% and grade 4 in 25.3%. High BD has been associated to younger age (p