Introduction: The Coronavirus disease (COVID-19) pandemic is a worldwide challenge. There are few useful tools to predict patient outcomes. Identification of biomarkers able to predict progression of ...the disease could improve the treatment of these patients. Objective: The objective of the study was to identify biomarkers of disease progression among patients with severe COVID-19 pneumonia. Materials and methods: A retrospective cohort study was conducted among severe COVID-19 pneumonia patients hospitalized in the American British Cowdray Medical Center in Mexico City. Disease progression was defined as use of vasoactive amines, need of non-invasive or invasive mechanical ventilation or death. Studied biomarkers included neutrophil/lymphocyte index, lymphocyte/platelet Ratio, C reactive protein, procalcitonin, D Dimer, lactic dehydrogenase (LDH), ferritin, 25–OH–Vitamin D, and interleukin 6. Results: We report 46 patients with severe COVID-19 pneumonia. Mean age was 51 years, the majority of whom 30 (65%) male. Median hospitalization was 9 days. 23 (50%) of patients presented disease progression. Ferritin and LDH were strongly associated with disease progression among our cohort. In addition, age was associated with worst prognosis with a relative risk 4.5 (1.2-16.9, p = 0.003). Conclusions: Age, ferritin, and LDH were associated with disease progression among patients with severe COVID-19 pneumonia.
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e12630
Background: The current standard of treatment for locally advanced and early HER2+ breast cancer is the use of neoadjuvant chemotherapy (NAC) in combination with trastuzumab and ...pertuzumab. Mexican reports about its efficacy and predictive factors leading to pathological complete response (pCR) are scarce and few statistics are known. Methods: We performed a retrospective review of medical records of locally advanced and early HER2+ breast cancer patients who were treated with NAC in association with pertuzumab and trastuzumab. pCR was defined as the absence of residual invasive cancer cells in the breast and lymph nodes (ypT0/ypN0). Other histopathological features included Tumor type, estrogen, and progesterone receptor expression, HER2 status and Ki67. Clinical data included age, body mass index and number of metastatic nodes. Results: Thirty-five patients with early or locally advanced HER2+ breast cancer diagnosed and treated in a Comprehensive Cancer Center between January 2014 to June 2020 were included. The median age in the population was 47 years (range 28-79) with 20 patients under 50 years (57% of the total population). 40% of the patients were classified as overweight or obese at the time of diagnosis. The predominant histology was infiltrating ductal carcinoma (91%). The most frequent clinical stages were IIA, (34.2%) IIB (31.4%) and IIIA (22.8%). The population included patients with N0 (21.7%), N1 (56.5%), N2 (13%) and N3 (8.7%). Most tumors were larger than 2 centimeters at the time of diagnosis. T1 (17.4%), T2 (60.9%), T3 (17.4%) and T4 (4.3%). Most of the patients (77%) had a high proliferation index (Ki67 > 20). A total of 12 patients (34.3%) were hormone receptor (HR) negative and the rest (65.7%) were categorized as Triple Positive. The chemotherapy schemes used for NAC treatment were AC/THP (57.5%), THP (22.8%), TCHP (17.1%) and FEC/THP (2.7%) pCR was achieved in 60% of the patients. Patients with HR (-) achieved a pCR in 83% of the cases (10/12 patients) against 47.8% (11/23 patients) of the triple positive population. The Odds ratio (OR) for residual disease was 6.6 (95%CI 1.17-37.02) in the HR+ population. HR-/HER2+ tumors (p = 0.49) were independent predictors of pCR at multivariate logistic regression. No other variables including Ki67, BMI, age, tumor size, type of chemotherapy administered, and lymph node status were statistically significant. Conclusions: In this Mexican population there is a significant difference between the percentage of patients who achieve pCR in relation to the status of hormone receptors, favoring those patients with hormone receptor negative tumors. Nevertheless, most of the population achieves this benefit regardless of their hormone status, as HER2+ tumors showed sensitivity to chemotherapy and to the humanized anti-HER2 therapies. No other clinical or pathological variables were associated with pCR.
Abstract
BACKGROUND: Breast cancer (BC) in young women has a behavior and biology associated with an increased risk of recurrence and death. The diagnosis of MC in young women is strongly associated ...with the presence of genetic mutations, mainly in the BRCA gene. However, an association between the presence of inherited genetic mutations and prognosis has not been observed. OBJECTIVE: To describe the prevalence and analyze the clinical-pathological characteristics of women, <50 years with BC, with and without BRCA germline mutation. MATERIAL AND METHODS: A descriptive, observational, cross-sectional study of women <50 years with BC with and without BRCA germline mutation who received treatment at a private third level Medical Center. RESULTS: During the period from January 1, 2015 to June 1, 2020, 807 women with a diagnosis of breast cancer were identified who received systemic treatment under adjuvant, neoadjuvant or palliative indication. Of these, 360 (44.6%) were 50 years old or younger. 53 women with BC <50 years had the result of a genetic panel and are the ones that were included for the analysis. Median age was 40 years (27-50), 55% <40 years old. The immunophenotype, according to the evaluation by immunohistochemistry of the hormonal receptors, Ki-67 and HER2/neu status, was luminal A like in 13 (24.5%) women, luminal B like in 18 (34%), luminal B like with overexpression of HER2/neu in 7 (13.2%), HER2/neu in 3 (5.7%) and in 12 (22.6%) cases it was triple negative. 30/53 women (56.6%), presented some mutation in the genetic panel. BRCA1 and/or BRCA2 9/30 (30%) mutation, all of them were pathogenic variants. Mutations other than BRCA in 21/30 (70%), of these 7/21 (33.3%) pathogenic (P) mutations in the ATM (2), MUTYH (2), TP53 (2) and PALB2 (1) genes. In 14/21 (66.7%) variants of uncertain significance (VUS) were identified. We did not observe an association between the clinicopathological characteristics and the BRCA mutational status or other genetic mutations, except for the high degree of differentiation (p = 0.04), being more frequent in the mutated group. There were no differences in disease-free time between BRCA mutated and non-mutated patients (p = 0.12). CONCLUSIONS: The prevalence of the BRCA germline mutation in women with BC <50 years in our population was 30%. The clinical and biological characteristics and the disease-free time were not different among the group with and without BRCA germline mutation, or other genes.
BRCA GENETIC VARIANTS (n:9)IDGenProtein changeNCBI 1000Clinical risk4BRCA1c.1960A>Tp.Lys654*rs80357355P16BRCA1c.815_824dupAGCCATGTGGp.Thr276Alafs*14rs387906563P38BRCA1c.211 A>Gp.Arg71Glyrs80357382P8BRCA2c.658_659delp.Val220llefs*4rs80359604P25BRCA2c.6024dupGp.Gln2009Alafs*9rs80359554P24BRCA1ex9-12del c.548?PBRCA2c.6413T>Ap.Val2138Asprs80358877VUS40BRCA2c.8988_8990delATAinsTTp.Leu2996Phefsrs397508027P42BRCA2c.5146_5149dep.Tyr1716LysFs*8rs276174854P49BRCA2c.6244delp.Leu2082fsrs1131691125PNO BRCA GENETIC VARIANTS (n:21)IDGENProtein changeNCBI 1000Clinical risk45ATMc.7502A>Gp.Asn2501Serrs531617441VUS48ATMc.3663G>Ap.Trp1221rs864622490P52ATMc.2839-3_2839delinsGATACTArs786202148PAPCc.1895T>Cp.Ile632Thrrs587781360VUS3ATMc.6919C>Tp.Leu2307Phers56009889VUSSMAD4c746_747delinsCCp.Gln249delinsPrors587782209VUS23BAP1c.623G>Ap.Arg208Glnrs867416499VUS32BRIP1c.3088_3096dupp.Ala1030_Ser1032duprs1187782159VUS36CDKN2Ac.146T>Cp.Ile49Thrrs199907548VUS5CHEK2c.1567C>Tp.Arg523Cysrs149501505VUS30DICER1c.1798G>Cp.D600HVUS22FANCMc.5832G>Tp.Leu1944Phers201017015VUS41FHc.1481C>Tp.Ala494Valrs752369363VUSTSC1c.2432G>Ap.Arg811Glnrs761281095VUS11MLH1c.2219T>Cp.Ile740Thrrs1044486319VUS12MUTYHc.1227_1228dupp.Glu4110Glyfs*43rs587780078P16MUTYHc.1227_1228dupp.Glu4110Glyfs*43rs587780078P20PALB2c.509_510delp.Arg17Ilefs*14rs515726123P14PMS2c.865T>Ap.Phe2891lers771787834VUS47POLEc.4150C>TVUS6RAD51Cc.492T>Gp.Phe164Leurs573992101VUS17TP53c.604C>Tp.Arg202Cysrs587780072VUS50TP53c.587G>Cp.Arg196Prors483352697P43TP53c.587G>Cp.Arg196Prors483352697PKDRc.1416A>Tp.Gln472Hisrs1870377VUS
Citation Format: Daniela Vazquez-Juarez, Juan A Serrano-Olvera, Alejandro Noguez-Ramos, Gabriela O Regalado-Porras, Jesus M Lazaro-León, Guillermo Olivares-Beltran, Raquel Gerson-Cwilich. Prevalence of BRCA 1/2 germinal mutation among young women with breast cancer: Experience in a third level private center abstract. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-07.
The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found ...in some studies.
This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point.
After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%).
Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.
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Background: Currently there are no primary cultures or cell lines derived from patients with breast cancer and obesity. It has been postulated that breast cancer in obese women ...behaves differently as it does in non-obese women, as is composed of distinct biological features, as was generated in a different metabolic environment, as well as pertains to a different prognosis and different response to chemotherapy, lower rates of overall survival and a greater probability of recurrence. By creating a primary breast cancer culture bank of breast cancer tumors from women with obesity (BMI > 30kg/m
2
), we will establish a cell line exclusive to obese women in Mexico, where targeted therapy may be tested and treatment may be individualized depending on the characteristics of the patient. Methods: This study recruited 32 women with breast cancer and a BMI > 30 kg/m
2
, matched by 6 controls with are non-obese women with breast cancer. Elegibility criteria was determined by women with breast cancer confirmed by pathology, who had not been subjected to prior treatment regarding the neoplasm. The breast cancer removing surgeries and the patients were selected from the ABC Medical Center in Mexico City and all procedures were approved by the research and ethics committee of the hospital in question. Results: Through extensive communication a cooperative protocol was established between the departments of surgery, oncology, pathology and nursing to coordinate efforts and be able to take a 2 – 5 mm sample of the breast tumor removed from the patient. To be able to distinguish cancer cells from non-cancer cells (epithelial cells, fibroblasts, adipocytes) the Hayflick limit was be utilized. Once a primary breast cancer culture was established, 12 million cells will be injected into the subscapular area of athymic, nu-nu mice to be able to monitor tumoral growth in vivo and conduct a subsequent cellular analysis, determining it still pertains to the same characteristics of the tumor from which it was obtained. Conclusions: A primary breast cancer culture repository from patients with a BMI > 30 kg/m2 was established. This is the first primary breast cancer culture for both Mexican and obese women with breast cancer, the first in vitro method of analysis of specific characteristics typical of the Mexican population. Translational research may now be conducted on these new tumoral cultures to create individualized therapy for women with the distinct, aforementioned characteristics.
e22517
Background: there are few reported series n women with breast cancer (BC) and COVID-19, a better prognosis has been observed, with a lower rate of hospitalization and mortality than other ...neoplasms. Methods: We conducted a restrospective, non-experimental, observational, single center, study with a sample of 69 patients with BC who had presented COVID-19, in the period between March 2020 to August 2021. Clinicopathological characteristics of patients with BC were compared between severe and non-severe covid 19 groups, as well as hospitalized and non-hospitalized patients. An analysis of possible risk factors associated with severe disease and hospitalization was performed. Results: 69 cases were reported, median age 52y, mean BMI 25.2, ECOG 0-1: 97%. Smoking history in 24%, diabetes and hypertension were the most frequent comorbidities. The most frequent histology was ductal carcinoma in 80.6%, 73.8% showed ER + and 69.3% PR +, HER2 was overexpressed in 9.2%. The early stages predominated, I 22 (31.3%), II 25 (37.3%), III in 12 (17.9%) and IV in 6 (9%). The most frequents symptoms of COVID-19 were fatigue 70.1%, fever 65.7%, cough 59.7%, headache 56.7%, hyposmia 47.8%, dysgeusia 38.8%. A total of 53 (76.8%) mild cases, 14 (20.3) severe cases and 2 (2.9%) critical cases were registered. The 89.9% (62 patients) were treated as an outpatient basis, while 7 (10.1%) required hospitalization. Active treatment (< 45 days) at the time of COVID-19 was hormonal therapy 36 (50.7%), chemotherapy 11 (16.4%), anti-HER2 in 3 (4.5%), immunotherapy in 1.5%, targeted treatment in 4 (6.0%), surgery in 7 (10.4%) and radiotherapy in 1 (1.5%) patient. When comparing the severe and non-severe groups, as well as hospitalized versus non-hospitalized, we observed no difference between the clinicopathological characteristics. Then, we serch for possible risk factors, in wich, surgery in a period of less than 3 months increases the risk of severity OR 1,297 (95% CI 1,112-1,514), the risk of hospitalization increased in the triple negative subgroup OR 1,143 (95% CI, 1,035- 1,262), surgery less than 3 months OR 1,116 (1,014-1,229) and chemotherapy less than 45 days OR 1,217 (95% CI, 1,024-1,447). Conclusions: In patients with BC, the prevalence of severe or critical COVID-19 was 23% and the hospitalizacion rate 10%. No patient died from this infection. The clinical and pathological characteristics of BC do not appear to increase the risk of severe COVID-19 or the rate of hospitalization. Surgery performed in a period of less than 3 months is marginally associated with an increased risk of severe disease. Chemotherapy, targeted therapy, and immunotherapy do not modify the risk of severe disease; however, higher Ki 67, triple negative subgroup, surgery and chemotherapy showed a slight increase in risk of hospitalization.
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Background: A relationship has been found between a better response to treatment and the presence of irAEs. Different potential factors for developing them have been described, including the ...type of immunotherapy and their combination. Rare (< 1%) and potentially life-threatening irAEs have been reported, which due to severity lead to treatment discontinuation, and a prolonged effective response is seen in these patients if they survive the irAE. Methods: Observational study in patients with solid tumors who received treatment with immune checkpoint inhibitor and their characteristic, that presented irAEs grade 3 and 4 using the CTCAE version 4, from January to December 2021 in a Mexican cancer center. Results: irAEs grade 3 or 4 were observed in 7 (5.6%) of 125 patients, with an age range of 60 to 69 years, most of the patients had a diagnosis of metastatic melanoma (43%) and secondly urothelial carcinoma with 29%. The predominant treatment was pembrolizumab monotherapy (56%), with an average of 5 applications after those who presented irAEs. The rare irAEs presented were myocarditis (2.4%), myositis (1.6%), myasthenia gravis and interstitial nephritis, both with 1%. 70% of these patients were managed with three boluses of methylprednisolone and subsequently prednisone 1 mg/kg as maintenance. The median appearance of these irAEs was 72 days. Myocarditis and myositis had an earlier onset with an average of 32 days. One of the seven patients presented myasthenia gravis, myositis and myocarditis concomitantly, with complete response of the neoplasia, however, due to the prolonged use of immunosuppressants to control irAEs, the disease recurred at 7 months. Two of the three patients with myocarditis had a complete response and remain disease free. 57% survived more than 90 days, of which 75% are still alive. Conclusions: Among the 125 patients who received an immune checkpoint inhibitor in our cancer center in 2021, the most prevalent serious irAE was myocarditis, with a higher incidence than that reported by other centers, and a prolonged therapeutic response was found in the patients who presented it.
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Background: Colorectal cancer (CRC) is the most common gastrointestinal neoplasia, with 1.36 million cases worldwide, representing the third cause of death due to cancer. ...Commonly affects people after the 6th decade of life, but recently the diagnosis in patients below 50 years is increasing. Methods: We conducted an observational, retrospective, longitudinal analysis based on medical records of patients diagnosed with colorectal cancer treated in the ABC Medical Center. Information was collected between January 2016 and January 2021. Descriptive statistics were utilized regarding data analysis. Results: We identified 289 patients with CRC, of which 23 (8.2%) patients were less than 50 years of age at diagnosis. Gender distribution reflected slightly more feminine patients (56%). The median age at diagnosis was 43 years, oncologic family history in first- or second-degree family members was documented in 31.4% of patients. At diagnosis, 22% of patients presented with an early-stage neoplasm, 31% had locoregional disease and 50% had advanced disease. Left sided disease was present in 78% of patients, 8% on the right colon and 13% were in rectum. Adenocarcinoma was found in 95% of patients. Mucinous pattern was present in 39% of patients studied, intestinal tumors in 21%, singlet ring cells in 4.3%. Histologic grade was G2: 69%. Molecular analysis was conducted in 86% of tissue biopsies. Regarding RAS mutations, 15% were positive (Gly12asp, K117N and Gly13Asp), but none in NRAS. BRAF mutation was studied in 43% of patients, no mutations were found. The search for microsatellite instability was conducted in all tumors, finding it present in only one patient (5%). At median follow up of 31.8 months, 91.4% remainded alive. Patients with early stage cancer were given adjuvant therapy in 69%. mean RFS was 40 months. All patients diagnosed in stage IV disease received systemic therapy, with a medium PFS of 10 months. First line treatment was FOLFOX in 58% of patients. Target therapy with anti-EGFR and anti-VEGF was prescribed in 83.3% and 8.3% of patients in the first line respectively. Conclusions: We found that patients under 50 years with dignosis of colorectal cancer, have a family history of cancer in up to a third of patients, the most frecuent histology reported was adenocarcinoma with mucinous pattern. We observed a low frecuency of KRAS mutations compared with literature reports. A longer follow-up is requiered to asses overall survival.
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Background: In México the 5-year overall survival of Early Breast Cancer (EBC) reaches to 82-97%. Oncotype Dx evaluates the expression of 21 genes associated with recurrence and ...classifies patients into risk groups. PREDICT (https://breast.predict.nhs.uk/tool) is an online tool which assesses 5 and 10 year overall survival in breast cancer patients who receive adjuvant chemotherapy, adjuvant hormonal therapy and trastuzumab therapy for HER2(+) patients. Methods: Retrospective review of medical records of early stage breast cancer patients with (HR+) and HER2 (-) treated at our institution. Clinicopathological characteristics and (RS) were collected. 5-year overall survival was calculated with the PREDICT online tool. Both scores were compared and the correlation was estimated with Spearman’s Rho and global agreement with intraclass correlation coefficient (CCI), statistical software: STATA SE ver11.0 (StataCorp LLC Texas,USA). Results: From January 2008 to December 2018, 136 patients with EBC (IA-IIB), HR(+) HER2(-), N0-1 were included. The Median age at diagnosis was 55.03 years (30-80). Stage IA patients accounted for 68.38% of the population. Patients were classified into risks according to the original description of Oncotype. 72 patients (53%) were classified as low risk (LR), 49 (36%) at intermediate risk (IR) and 15 (11%) patients at high risk (HR). When reclassifying the risk categories using the cut-off values in TAILORx trial, the population distribution was modified, with a notable increase in the population in IR with 86 (63.2%) patients in this group, 28 patients in the LR group ( 20.5%) and 22 patients (16.1%) in HR. We decided to use TAILORx cut-off values for the aim of this work. Mean overall survival established by the 21 gene RS was 98% for the overall population. The mean overall survival calculated by PREDICT was 93%. Spearman’s correlation coefficient was 0.16 (Spearman’s Rho = 0.16 p = 0.065) with intraclass correlation coefficient (ICC) = 0.04 (IC 95% -0.15 – 0.22, p = 0.33). Conclusions: The results do not show a clear correlation between the tests. Lack of such correlation may be due to a low number of patients. In our population PREDICT couldn't replace the RS test for therapeutic decision making.
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e12539
Background: The 21-gene test is clinically validated to predict chemotherapy (CT) benefit in node-negative (N0) and node-positive (up to 3 axillary nodes, N+) HR+, HER2− ...early-stage breast cancer (ESBC). TAILORx showed no CT benefit overall in N0 patients with RS 0-25, but younger patients with RS 16-25 might have some. Clinical guidelines worldwide incorporate the 21-gene test; still, the impact of the test on treatment decisions is unclear in Latin America, where patients often present younger and with more advanced disease. We present a physician survey of the impact of Recurrence Score results on treatment decisions in clinical practice in Latin America. Methods: This multicenter, non-therapeutic, prospective survey enrolled consecutive patients who had 21-gene testing during routine care at 14 community and academic sites in Argentina, Colombia, Mexico, and Peru. Tests were paid for by patients. The physician survey captured patient and tumor characteristics and treatment decisions by physicians pre- and post-assay result. The survey included patients treated before and after TAILORx results reported in 6/2018. Overall net percent change in CT recommendation and 95% Clopper Pearson confidence intervals (CI) were estimated. The proportion with a change between pre-assay treatment recommendation and actual treatment received was calculated overall and by Recurrence Score groups per TAILORx. Results: Between 3/2015 and 12/2019, the survey was completed for 647 patients. 20% had N+ ESBC. Mean patient age was 54 y (24-85 y); 55% were postmenopausal. 17%/63%/20% had grade 1/2/3 tumors; 70%/30% had tumors ≤2/ > 2 cm in size. Recurrence Score results were: 20% RS 0-10, 56% RS 11-25, and 24% RS 26-100. Overall, CT recommendations fell from 325 patients pre-assay to 199 patients post-assay, a 39% decrease (95% CI 33.4 to 44.3) (36% decrease in N0; 46% decrease in N+). The direction of change was consistent with Recurrence Score results. Among N0 patients, the decrease in CT recommendations was 28% (95% CI 18.9 to 39.5) before TAILORx reported and 36% (95% CI 28.4 to 43.7) after. Conclusions: This large survey of 21-gene test practice patterns was the first conducted in Latin America and showed the relevance of 21-gene testing in low- and medium-resource countries to minimize CT over- and underuse in ESBC. Our results showed substantial reductions in CT use overall. After TAILORx, CT use was further reduced, indicating the practice-changing potential of that study.
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