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IntroductionMetastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies.MethodsWe sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing.ResultsOverall, we found 22 variants –9 of them reported for the first time– and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort.DiscussionOur results reflected the unique characteristics of the Mexican-mestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population. more...

BACKGROUND The current study was performed to identify factors that are present at the time of breast cancer (BC) diagnosis that are associated with a higher rate of central nervous system metastasis (CNSm). METHODS The authors analyzed a database of patients with a confirmed diagnosis of BC who were referred for a neuro-oncology consultation at the National Cancer Institute in Mexico City, Mexico, from June 2009 to June 2017. Information was collected prospectively and included demographic, pathologic, and clinical data at the time of diagnosis of BC. Bivariate and multivariate logistic regression models were built to estimate the associations between the development of CNSm and the time after BC diagnosis. RESULTS Among 970 patients with BC, 263 (27%) were diagnosed with CNSm. The median time from BC diagnosis to the development of CNSm was 33 months (interquartile range, 15-76 months). After multivariate analysis, age more...

Pregnancy-associated breast cancer (PABC) poses a clinical challenge and its prognosis remains controversial. During the pregnancy and postpartum periods, the breast undergoes biological events that may uniquely influence disease behavior and treatment response. This study aimed to assess if a PABC diagnosis influences survival compared to non-PABC. A single-center record review was performed to identify PABC patients diagnosed from January 2007 through June 2018. Two controls were matched to each PABC case by stage, immunohistochemical (IHC) subtype, age (± 3) and year of diagnosis (± 2). Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan–Meier method and compared with the log-rank test. Multivariate analysis was used to assess the impact of PABC on outcomes. 125 PABC patients (pregnant: 62; postpartum: 63) and 250 controls were included. Median follow-up was 67.7 and 73.4 months, respectively. 4-year DFS was 62% in pregnant vs 78% in controls (p = 0.010), and 63% in postpartum vs 83% in controls (p = 0.034). Subanalysis by IHC subtype revealed a significantly inferior DFS in PABC with hormone receptor-positive/HER2-negative (p = 0.032) and HER2-positive disease (p = 0.005) compared to corresponding non-PABC patients. 4-year OS was similar between case groups and controls. Multivariate analysis supported the independent impact of pregnant and postpartum status on DFS (p more...

Background: CNS metastases are reported in about 10 to 15%. Knowledge about the management of these patients are limited because they are excluded from clinical trials due to its poor prognosis and morbidity. In these study, we aim to describe characteristics, treatment patterns, and overall survival (OS) of patients of mBC with CNS metastases at Instituto Nacional de Cancerología de Mexico (INCan) from january 2007 to december 2015. Methods: We include patients with histological diagnosis of mBC and tumoral activity in the CNS (at diagnosis or during de follow-up). mBC subtype was defined using HER2 and hormone receptor (HR) status by immunohistochemistry; systemic treatment, and mortality data were used to characterize mBC with CNS involment. Results: During the study period, we found 1272 patients diagnosed with metastatic disease, of whom 408 had CNS disease (novo/recurrence) the median follow up was 52 months. Table 1 describes the percentage of CNS metastases by subtype, clinical characteristics at diagnosis and median OS. Almost all patients (85.6%) were candidate to holocranial radiotherapy; after that, systemic treatment varied according to the subtype of mBC; 69.1% of TN received CT (26% based on platinum); 75.3% of HER2+ received systemic treatment, all included antiher2 therapy; luminal subtype, no one were treated with endocrine therapy. Table 1.- characteristics and Overall suvival by subtype of mBC all mBC 1272 n(%)her2 positive 339 (26.6) n (%)triple negative 298 (23.4) n(%)luminal 636 (50) n(%)CNS metastasis at dianosis44 (3.5)12 (3.5)13 (4.4)19 (2.9)CNS mets after prog to systemic tx205(16.1)63(18.6)50(16.7)92(14.5)CNS as first place of recurrence159(12.5)75(22.2)34(11.4)50(7.8)prevalence on CNS mets408(10.7)150(14.7)97(10.8)161(8.4)median age at diagnosis of CNS mets50(28-84)50(29-84)48(28-80)51(28-80)median OS after CNS mets (months)14.927.29.3316.3 Conclusions: HER2 positive breast cancer patients have the highest prevalence of CNS metastases, whereas luminal has the lowest. Patients with HER2+ and CNS metastases commonly receive treatment based on anti-HER2 therapy, maybe this target treatment contribute to the better survival achieved than patients with luminal or TN subtype. mBC with CNS metastases continues in the real world to be an unmet medical need. Citation Format: Alvarado-Miranda A, Cabrera-Galeana P, Muñoz-Montaño WR, Lara-Medina F, Bargallo-Rocha E, Arrieta-Rodriguez O, Perez M, Porras-Reyes F, Mohar-Betancourt A, Gamboa C. Real-world characteristics, treatment patterns, and overall survival in patients with metastatic breast cancer (mBC) and CNS metastases [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 P1-19-07. more...

Although the epidemiology of breast cancer in older women has been widely described before, little is known about the clinical characteristics and prognosis of older patients living in developing countries. Here, we studied older women with breast cancer treated at a public cancer center in Mexico City, and compared their outcomes with their younger counterparts.We retrospectively analyzed a database of 5488 women treated for breast cancer at a single institution. We compared clinical characteristics, treatment and survival between women aged65 and ≥65 years of age. Survival analyses were performed for each molecular subtype.851 women (15.5%) were ≥65 years of age, of which 45% presented with Stages III-IV disease. Compared with their younger counterparts, older women had lower grade disease, a larger proportion of hormone receptor positive tumors, and were less likely to receive both chemotherapy and radiotherapy. At 5 years, no differences in both disease free and overall survival were found between younger and older women in a multivariate model including stage, grade, tumor subtype and treatment received.In contrast with reports from high-income countries, older women with breast cancer in developing nations present with more advanced disease requiring more aggressive treatment. Strategies aimed at earlier detection, improved access to care, and downstaging among older adults are greatly needed in Mexico and in the rest of the developing world. more...

Background Several breast cancer (BC) trials have adopted pathological complete response (pCR) as a surrogate marker of long-term treatment efficacy. In patients with luminal subtype, pCR seems less important for outcome prediction. BC is a heterogeneous disease, which is evident in residual tumors after neoadjuvant-chemotherapy (NAC). This study evaluates changes in Ki67 in relation to disease-free survival (DFS) and overall survival (OS) in patients without pCR. Subjects, Materials, and Methods Four hundred thirty-five patients with stage IIA–IIIC BC without pCR after standard NAC with anthracycline and paclitaxel were analyzed. We analyzed the decrease or lack of decrease in the percentage of Ki67-positive cells between core biopsy samples and surgical specimens and correlated this value with outcome. Results Twenty-five percent of patients presented with luminal A-like tumors, 45% had luminal B-like tumors, 14% had triple-negative BC, 5% had HER2-positive BC, and 11% had triple-positive BC. Patients were predominantly diagnosed with stage III disease (52%) and high-grade tumors (46%). Median Ki67 level was 20% before NAC, which decreased to a median of 10% after NAC. Fifty-seven percent of patients had a decrease in Ki67 percentage. Ki67 decrease significantly correlated with better DFS and OS compared with no decrease, particularly in the luminal B subgroup. Multivariate analysis showed that nonreduction of Ki67 significantly increased the hazard ratio of recurrence and death by 3.39 (95% confidence interval [CI] 1.8–6.37) and 7.03 (95% CI 2.6–18.7), respectively. Conclusion Patients without a decrease in Ki67 in residual tumors after NAC have poor prognosis. This warrants the introduction of new therapeutic strategies in this setting. Implications for Practice This study evaluates the change in Ki67 percentage before and after neoadjuvant chemotherapy (NAC) and its relationship with survival outcomes in patients with breast cancer who did not achieve complete pathological response (pCR). These patients, a heterogeneous group with diverse prognoses that cannot be treated using a single algorithm, pose a challenge to clinicians. This study identified a subgroup of these patients with a poor prognosis, those with luminal B-like tumors without a Ki67 decrease after NAC, thus justifying the introduction of new therapeutic strategies for patients who already present a favorable prognosis (luminal B-like with Ki67 decrease). more...

Background Older patients with breast cancer treated in high-income countries often present with early-stage disease, leading to a lack of information on the use of neoadjuvant chemotherapy in this population. We analyzed the real-world outcomes of older women with breast cancer treated with neoadjuvant chemotherapy at a single institution in Mexico. Materials and Methods The study included 2,216 patients treated with neoadjuvant chemotherapy. Regarding achievement of pathologic complete response (defined as no invasive residual tumor in the breast and lymph nodes), 243 patients aged ≥65 years were compared with 1,973 patients aged Results Older women were less likely to have a pathologic complete response than their younger counterparts (26.3 vs. 35.3%, p < .001). When response rates by subtype were analyzed, this difference was significant only for women with triple-negative tumors. Achieving less than a pathologic complete response was associated with a greater chance of recurrence, but age was not an independent factor for recurrence for any subtype. Reaching a pathologic complete response was significantly associated with improved survival among older women with breast cancer, with the exception of those with hormone receptor–positive, HER2− disease. Conclusion Although older women have fewer pathological complete responses, their outcomes after neoadjuvant chemotherapy are comparable to those of younger patients. This is particularly relevant for the treatment of older adults with breast cancer in developing countries, who present in advanced stages and more often need neoadjuvant therapy. Implications for Practice The majority of older patients with breast cancer in high-income countries present with early-stage disease, leading to a lack of information regarding the use of neoadjuvant chemotherapy in real-world settings. This article reports the outcomes of older Mexican women with breast cancer who received neoadjuvant chemotherapy compared with their younger counterparts. Although older women (particularly those with triple-negative tumors) were less likely to have a pathologic complete response after neoadjuvant treatment, age was not an independent factor for recurrence. Achieving a pathologic complete response was associated with improved survival, regardless of age. more...

The aim of this study was to determine the benefits of supplementation with eicosapentaenoic (EPA) and docosahexaenoic (DHA) polyunsaturated fatty acids (PUFA) in terms of chemotoxicity and inflammatory status, to Mexican women with locally advanced breast cancer (LABC), receiving a standard neoadjuvant chemotherapy (NeoCT AC-taxol regimen). We performed a randomized double-blind, placebo-controlled, clinical trial, in which we studied 44 LABC patients (stages IIA to IIIA) who took 2.4g/d (1.6 g EPA and 0.8 g DHA, ratio 2:1) (N=22) or placebo (N=22) during NeoCT with doxorubicin/ cyclophosphamide followed paclitaxel weekly. Edmonton Scale and Common Terminology Criteria for Adverse Events (CTCAE) v4. assessment were performed before each CT, and also blood total leukocytes, and percentage lymphocytes and monocytes by standard lab methods. Serum inflammatory proteins and adipokines, were quantified by multiplexed analysis using a luminometer (MAGPIX) at basal time (0) and after cessation (+6 months) of AC and paclitaxel regimen. RESULTS: There were no differences in age between the supplemented and the placebo groups (51.6y vs. 49.1y, p=0.4), neither in body mass index (BMI, 28.7 kg/m2 and 28.9 kg/m2, p=0.8). After 6 months of supplementation, patients who were supplemented with PUFAs had significant changes (time 0 vs 6, respectively) in total leukocytes (from 6.3 to 5.1 x103/mL, p =0.002) lymphocytes (from 33.5 to 25.2%, p =0.002), leptin (from 60.2 to 36.1 pg/mL, p=0.04) and adiponectin (from 36.8 to 43.3 mg/mL, p=0.05 ). On the other hand, placebo group had significant changes in the number of leukocytes (from 6.8 to 10.0 x103/mL, p =0.04), monocytes (from 6.7 to 10.1%, p=0.03) and an increase in leptin (from 22.7 to 46.3 pg/mL, p=0.04). CONCLUSIONS: Supplementation with 2.4g/d of EPA and DHA (ratio 2:1) during 6 months in Mexican LABC patients receiving NeoCT resulted in a less inflammatory status when compared to patients who received none. Our results clearly suggest that this type of supplementation may be beneficial to these type of patients. Currently, we are analyzing if treatment with omega-3 PUFAs are associated with lower incidence of side effects due to chemotherapy. Citation Format: DelaRosa-Oliva F, Ruiz-Garcia E, Gomez E, Arce-Salinas C, Lara-Medina F, Alvarado-Miranda A, Matus-Santos J, Flores-Díaz D, Deneken-Hernandez Z, Bargalló- Rocha J, Cabrera P, Guadarrama-Orozco J, Ruiz-Calzada H, Meneses-García A, Astudillo-de la Vega H. Effect of supplementation with eicosapentaenoic and docosahexaenoic omega-3 polyunsaturated fatty acid on the chemotoxicity in Mexican patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (NeoCT) [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 P2-11-10. more...

Purpose Neutrophils are among the key cellular players in the inflammatory milieu produced in patients with breast cancer (BC), and strong evidence exists in terms of the prognostic value of assessing the neutrophil-to-lymphocyte ratio (NLR) in patients with BC. In this study we sought to determine whether the baseline NLR correlates with pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS) in patients with locally advanced BC in the neoadjuvant chemotherapy (NAC) setting. Methods We analyzed the pretreatment NLR from the first blood count of patients treated from 2007 to 2015 in terms of pCR, DFS, and OS in patients with locally advanced BC. Patients received standard medical care based on national guidelines. Results A total of 1519 patients were included in the study. Median age was 49 years (22-88). The cutoff point for NLR was 2.0. NLR was not associated with pCR or DFS. However, patients with high NLR had worse OS in the presence of triple-negative BC (105.9 months; 95% confidence interval [CI], 100.2-111.5] vs. 98.7 months; 95% CI, 91.1-106.3; P = .029), Her2 overexpression (114.0 months; 95% CI, 110.5-118.0 vs. 100.8 months; 95% CI 95.7-105.9; P = .019), and residual disease after NAC for both phenotypes. Multivariate analysis showed that NLR was independently associated with OS (hazard ratio, 1.4; 95% CI, 1.02-1.95; P = .037). Conclusions Pretreatment NLR in patients with locally advanced BC correlates with OS as an independent prognostic factor. This influence depends on phenotype and residual disease. Routine assessment of this parameter could be an easy and affordable tool for defining prognosis. more...

Metastatic breast cancer (MBC) is a challenge for oncologists, and public efforts should focus on identifying additional molecular markers and therapeutic management to improve clinical outcomes. Among all diagnosed cases of breast cancer (BC; approximately 10%) involve metastatic disease; notably, approximately 40% of patients with early‑stage BC develop metastasis within 5 years. The management of MBC consists of systemic therapy. Despite different treatment options, the 5‑year survival rate is more...

El paclitaxel incrementa la supervivencia en cancer de mama. Su aplicacion semanal es mejor tolerada y eficaz. Uno de cada 5 pacientes tendra neutropenia y uno de cada 15 tendra neutropenia febril. El objetivo fue identificar factores de riesgo desarrollar neutropenia (NP) III-IV. Materiales y metodos: 257 pacientes utilizaron paclitaxel semanal con biometria hematica (BH) previa a la infusion durante las 12 semanas. Se determino edad, etapa clinica, comorbilidad, IMC, dosis total, dosis/m2 SC, numero de consultas, visitas a Urgencias y hospitalizaciones. Resultados: 118 pacientes (45.9%) recibieron paclitaxel neoadyuvante, adyuvante 86 (33.4%) y paliativo primera linea 53 pacientes (20.6%). La frecuencia de NP III-IV fue del 5.9%. El analisis multivariante identifico como variables independientes para NP III-IV: edad (mayores de 60 anos) (OR: 3.11; IC 95%: 1.05-9.20; p = 0.04), quimioterapia previa (OR: 3.74; IC 95%: 1.15-12.1; p = 0.027), ser hipertenso (OR: 6.63; IC 95%: 2.18-20.15; p = 0.001). Conclusiones: En los pacientes mayores de 60 anos, la exposicion previa a quimioterapia y la hipertension son factores de riesgo para el desarrollo de NP III-IV. La baja incidencia de NP III-IV en la practica clinica diaria durante la aplicacion de paclitaxel semanal sugiere una reconsideracion de la evaluacion semanal con BH en pacientes sin factores de riesgo more...

espanolIntroduccion: uno de los tratamientos para el cancer de mama localmente avanzado (CMLA), es la quimioterapia neoadyuvante (QTNeo). Sin embargo, los efectos secundarios afectan el estado funcional y la calidad de vida de los pacientes, especialmente por el estado inflamatorio que originan. En este trabajo se administraron los acidos grasos poliinsaturados omega 3 (AGPI Ω-3), ya que modulan negativamente algunas vias moleculares como las que inducen la activacion del factor nuclear-kappa B (NF-κB), involucrado con los mecanismos de toxicidad secundaria a la administracion de antraciclinas. Objetivo: valorar el efecto de los AGPI n-3, sobre la toxicidad de la QTneo, la composicion corporal, el perfil cardiometabolico y la calidad de vida en mujeres con CMLA durante la QTNeo. Metodos: se incluyeron cincuenta y tres mujeres con CMLA, en un estudio clinico doble ciego controlado con placebo. Las pacientes recibieron aleatoriamente 2,4 g/dia de AGPI Ω-3 (EPA 1,6 g y DHA 0,8 g) o placebo durante la quimioterapia neoadyuvante con adriamicina/ciclofosfamida seguido de paclitaxel +/- trastuzumab. Se evaluaron los eventos adversos relacionados con la quimioterapia mediante los Criterios de terminologia comun para eventos adversos (CTCAE, version 4.03) y la escala Global subjetiva del Sistema de Evaluacion de los Sintomas de Edmonton (ESAS), la composicion corporal y la toxicidad cardiometabolica. Resultados: no hubo diferencias significativas entre los grupos en los parametros de toxicidad hematologica y antropometricos. La xerostomia de la escala de Edmonton, presento una mejora significativa (p = 0,032) en los pacientes suplementados con AGPI Ω-3. Conclusion: la suplementacion con AGPI Ω-3 no mostro cambios en la composicion corporal ni en la toxicidad del tratamiento neoadyuvante, solamente se encontro una mejoria significativa en la xerostomia. EnglishBackground: antineoplastic treatment for locally advanced breast cancer (LABC) includes neodjuvant chemotherapy (NeoCT). However, side effects occur frequently, affecting the functional capacity and quality of life of patients as a result of the proinflammatory state of this therapy. In this work, omega-3 polyunsaturated fatty acids (PUFA Ω-3) were administered as they have been reported to modulate some molecular pathways such as nuclear factor-kappa B (NF-κB), which is associated with toxicity secondary to the administration of anthracyclines. Objective: to evaluate the effects of PUFA Ω-3 on the toxicity, side effects, body composition, cardiometabolic profile and quality of life in women with LABC after NeoCT. Methods: fifty-three women with LABC were included in a double-blinded, placebo-controlled clinical trial. Patients randomly received 2.4 g/day of PUFA Ω-3 (EPA 1.6 g and DHA 0.8 g) or placebo during NeoCT with adriamycin/cyclophosphamide followed by paclitaxel+/-trastuzumab. Adverse effects related to chemotherapy were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) and the Subjective Global Scale of the Edmonton Symptom Assessment System (ESAS). Body composition and cardiometabolic blood profile were also evaluated. Results: no significant differences were found between groups in the hematological and anthropometric toxicity parameters. Within the Edmonton scale, xerostomia presented a significant improvement (p = 0.032) in patients supplemented with PUFA Ω-3. Conclusion: supplementation with PUFA Ω-3 showed no change in body composition, cardiometabolic profile or toxicity due to NeoCT. It only showed significant improvement in xerostomia. more...

Evidence regarding the outcomes of Hispanic women with breast cancer is lacking. We analyzed women with HER2+ disease treated with trastuzumab-based neoadjuvant chemotherapy in Mexico.244 patients were included. Outcomes were compared between patients who achieved pathologic complete response (pCR) (n = 119), or less than pCR (n = 125). Patients with noninvasive (ypT0/is, ypN0) residual disease were also analyzed.119 (48.8%) patients achieved pCR. pCR was the only factor associated with improved 3 year survival (98.1% vs 92.3%: P = 0.02). Survival was better in patients with ypT0/is, ypN0 response than in those with residual invasive disease (p 0.01). 3 year survival was 98.1% for patients with pCR and 92.6% for patients with ypTis, ypN0 response (p = 0.64).Response rates to trastuzumab based neoadjuvant chemotherapy in Hispanics mimic that of other ethnic groups. This underlines the fact that access to treatment, rather than ethnicity, is the main prognostic factor in this population. more...

Purpose One half of the Mexican population lacks comprehensive health care coverage. In 2003, a reform to the General Health Law was approved that led to the creation of the System of Social Protection in Health and made universal health coverage mandatory. The main innovation of this reform was Seguro Popular, which provided coverage for breast cancer. Here we report the outcomes of women with breast cancer treated at a cancer center in Mexico under Seguro Popular. Materials and Methods This was a retrospective cohort study that included all patients with breast cancer treated in the Instituto Nacional de Cancerología in Mexico City between January 2007 and December 2013 with Seguro Popular coverage. Demographic and clinical information were collected and survival outcomes were analyzed. Results A total of 4,300 women with breast cancer were included in this analysis. Most patients had locally advanced disease at diagnosis (53%, n = 2,293), and 13% (n = 558) presented with stage IV disease. Neoadjuvant chemotherapy was administered to 1,834 patients (52%), with a pathologic complete response in 25.1% (n = 460). Median follow-up was 40.5 months. Five-year survival for the entire cohort was 82% (95% CI, 81% to 84%). Five-year survival was 97% for early-stage disease (95% CI, 95% to 98%), 82% for locally advanced disease (95% CI, 80% to 84%), and 36% for metastatic disease (95% CI, 30% to 42%). Conclusion This represents the first description of a cohort of patients with breast cancer treated in Mexico under Seguro Popular. Seguro Popular has allowed our institution, and other Mexican centers, to establish efficient standardized mechanisms to treat patients with breast cancer. more...

Neoadjuvant chemotherapy aims to improve the outcome of breast cancer patients, but only few would benefit from this treatment. Pathological complete response has been proposed as a surrogate marker for the prediction of long-term clinical benefits; however, 50%–85% patients have an unfavorable pathological complete response to chemotherapy. MicroRNAs are known biomarkers of breast cancer progression; nevertheless, their potential to identify patients with pathological complete response remains poorly understood. Here, we investigated whether a microRNA profile could be associated with pathological complete response in triple-negative breast cancer patients receiving 5-fluorouracil, adriamycin, cyclophosphamide–cisplatin/paclitaxel as a novel neoadjuvant chemotherapy. In the discovery cohort, the expression of 754 microRNAs was examined in tumors from 10 triple-negative breast cancer patients who achieved pathological complete response and 8 without pathological complete response using TaqMan Low-Density Arrays. Unsupervised hierarchical cluster analysis identified 11 microRNAs with significant differences between responder and no-responder patients (fold change ≥ 1.5; p more...

Young age represents an adverse prognostic factor in breast cancer (BC), and young women present with more advanced and aggressive disease. In Latin America, BC is increasing in young women, and there is a lack of information regarding the characteristics and outcomes of this patient population.We retrospectively analyzed a database of 4315 women treated for BC at a single institution. We compared clinical characteristics, treatment, and survival between women ≤ 40 and40 years of age. Survival analyses were performed for each molecular subtype.A total of 662 women (15.3%) were ≤ 40 years old. Younger women had more advanced disease, higher grade, and a larger proportion of luminal B and triple-negative tumors (P .001). At 5 years, both disease-free and overall survival (OS) were lower in younger women, although there were no differences after adjusting for stage. Five-year OS was worse for young women with hormone receptor-positive, human epidermal growth factor receptor 2-negative subtype (82% vs. 87.1%; P = .03), but not for those with human epidermal growth factor receptor 2-positive or triple-negative disease. This difference can be attributed to luminal B tumors, which showed a worse 5-year OS in younger women (79.1% vs. 85.2%; P = .03).Although young Mexican patients with BC have more aggressive disease at presentation than older women, only those with luminal B tumors have a worse survival after adjusting for stage. Strategies aimed at downstaging the disease and at improving the treatment of luminal B tumors in this population are needed. more...

Prognosis in patients with carcinomatous meningitis (CM) is poor, and numerous prognostic factors for response and survival have been described, but remain controversial. In general, series are small and involve a heterogeneous type of solid neoplasms. The purpose of this study was to describe a series of patients with breast cancer-associated CM to determine the clinical features and prognostic factors associated with survival. We conducted a retrospective study on 49 patients diagnosed between January 2003 and December 2007 at the Instituto Nacional de Cancerologia in Mexico City. CSF cytopathology samples were re-reviewed to confirm the diagnosis. Overall survival (OS) for patients with breast cancer with CM was 7 weeks. Factors independently associated with better OS included absence of encephalopathy at diagnosis (11 weeks versus 1 week; p = .036), low CSF protein content (15 versus 5 weeks; p = .022), and nontriple-negative receptor status in the primary breast cancer tumor (13 versus 3 weeks; p = .015). According to multivariate analysis, patients were divided into favorable and poor prognostic groups, with OS of 14 weeks and 2 weeks, respectively (p more...

e13099Background: Pregnancy-associated breast cancer (PABC) includes breast cancer diagnosed during pregnancy or within one or two years after delivery. PABC is the second most common malignancy di... more...

Breast cancer in young women has been shown to have an aggressive behavior and worse prognosis. Studies evaluating young women enrolled in clinical trials of neoadjuvant chemotherapy have shown that age is a determinant factor in the achievement of a pathological complete response (pCR). In this study, we sought to analyze the outcomes of young patients treated with neoadjuvant chemotherapy at a single institution. 1639 patients treated with neoadjuvant chemotherapy were included. 316 patients ≤40 years were compared with 1323 patients aged >40 years regarding the achievement of a pCR (defined as no invasive residual tumor in the breast or lymph nodes). Disease-free survival (DFS) and overall survival were compared between groups according to pCR status and subtype, defined by hormone receptor (HR) and HER2 status. Young women were more likely to have a pCR than their older counterparts (37.4 vs. 26.3 %, P < 0.001). This difference was significant both for HR+/HER2− and triple-negative (TN) tumors. Young age and achieving less than pCR were associated with a greater chance of recurrence for the entire population. Age was not an independent factor for recurrence in TN and HER2+ disease. However, being younger than 40 increased recurrence risk in HR+/HER2− tumors. The achievement of a pCR was not associated with improved DFS in young women with HR+/HER2− tumors. Although young women have a high rate of pCR, they also have a worse prognosis. In a real-world clinical setting, the achievement of a pCR was an independently significant protective factor for recurrence across all subtypes and ages, except for HR+, HER2− disease in young women. more...

Objetivo. Evaluar los factores pronósticos (características clínico-patológicas y tratamientos) en las pacientes con cáncer de mama y metástasis al sistema nervioso central (SNC) como primer sitio de afección. Material y métodos. Cohorte retrospectiva, formada por 125 pacientes con cáncer de mama atendidas en el Instituto Nacional de Cancerología durante 2007-2015, quienes presentaron afección en el SNC como primer sitio de metástasis. A través del método Kaplan-Meier y tablas de vida se estimó la supervivencia global. El modelo de riesgos proporcionales de Cox fue utilizado para determinar los factores pronósticos. Resultados. La mediana de super­vivencia global fue de 14.2 meses (IC95% 11.8-26.9). Pacientes clasificadas por inmunohistoquímica como triple negativo (TN) presentaron tiempos de supervivencia más cortos (p more...

e12023Background: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with pancreatic, colorectal, lung, gastric cancer and renal cell carcinoma. The aim of this study was to determine the relationship between pathological complete response (pCR) and pretreatment NLR values with overall survival in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NACT) at the National Cancer Institute (NCI) of Mexico. Methods: Data were retrospectively collected from the Database of the NCI for LABC patients treated with NACT (including trastuzumab for HER2+ tumors) between January 2007- December 2010. We evaluated data of 690 patients (pts). Patients without complete pathology reports, laboratory test results, inflammatory (T4d) or pregnancy related BC were excluded. Pts who were diagnosed with chronic liver disease, end stage renal disease or any inflammatory disease such as SLE were also excluded. The pretreatment blood count data was retrieved from ... more...

In our country breast cancer represents a major health problem. Only 45% of all population has access to health services, the consequence is delay in diagnosis and treatment. In Mexico, 66% of all new cases of breast cancer are diagnosed in locally advanced stages. From May 2007 the Health System Protection Against Catastrophic Expenses, called Seguro Popular (SP), breast cancer was included in covering the treatment of this neoplasm in any patient without access to social security.To evaluate the results and impact of SP in the adjuvant and neoadjuvant treatment of a group of patients diagnosed with breast cancer at an institution of national reference.We analyzed a group of 259 patients in stages (I-IIIC). The clinical stages I and II (55 patients) were treated with adjuvant chemotherapy FAC -T (fluorouracil 500 mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2 (FAC) followed by 12 weeks of paclitaxel 80 mg/m2 +/- trastuzumab loading dose of 4 mg/kg followed by 2 mg/kg); 204 patients in locally advanced stages (IIB-IIIC) received FAC-T +/- trastuzumab followed by surgery. Adjuvant treatment consisted of endocrine therapy for hormone-sensitive patients and radiotherapy 50 cGy according to international standards.The age at diagnosis was 47 years (range 23-68). 80% of them were locally advanced stages (IIB-IIIC) and were treated in a neoadjuvant setting, 20% was in early stages, treated with surgery and adjuvant chemotherapy The disease-free survival and overall survival at 30 months was 85.7 and 90% respectively. Overall pathologic complete response was obtained in 15% of cases. In the subgroup analysis showed that 41% of patients HER2 (+), 29% of triple-negative patients and 9% of hormone-sensitive tumors achieved complete pathological response (p = 0.0001).This is the first analysis of efficacy of adjuvant and neoadjuvant treatment in breast cancer since the introduction of popular secure non-entitled population. It is clear that treatment efficacy is similar to that reported in the literature, with 15% of pRC and survival to 30 months in 94-80%. The coverage of health expenditures treats a larger number of patients optimally. Along with this, efforts should be made to reduce the high frequency of diagnosis at advanced stage. more...

Prognosis in patients with carcinomatous meningitis (CM) is poor, and numerous prognostic factors for response and survival have been described, but remain controversial. In general, series are small and involve a heterogeneous type of solid neoplasms. The purpose of this study was to describe a series of patients with breast cancer-associated CM to determine the clinical features and prognostic factors associated with survival. We conducted a retrospective study on 49 patients diagnosed between January 2003 and December 2007 at the Instituto Nacional de Cancerología in Mexico City. CSF cytopathology samples were re-reviewed to confirm the diagnosis. Overall survival (OS) for patients with breast cancer with CM was 7 weeks. Factors independently associated with better OS included absence of encephalopathy at diagnosis (11 weeks versus 1 week; p = .036), low CSF protein content (15 versus 5 weeks; p = .022), and nontriple-negative receptor status in the primary breast cancer tumor (13 versus 3 weeks; p = .015). According to multivariate analysis, patients were divided into favorable and poor prognostic groups, with OS of 14 weeks and 2 weeks, respectively (p .001). These factors can identify a subgroup of patients who are candidates for an intensive management approach. more...

Background Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC. Methods One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg), and 6–8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. Results Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2–50.5%) and, 29.5% (95% CI, 21.4–37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR = 3.8; 95% CI, 1.5–9; p = 0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2–84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR = 3.1; 95% CI, 1.02–9.74; p = 0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75–93.2%). The toxicity profile was acceptable. Conclusion This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted. more...

e12024 Background: Triple negative breast cancer in our center represents 21% of all breast cancer cases. In these group of patients, its been suggested that cisplatin could improve breast cancer o... more...

e11577 Background: Although late-stage at diagnosis and aggressive histologic subtypes partially explain the poor prognosis in young women with breast cancer (BC), other biological differences may ... more...

Intraocular metastases are the most common malignancy of the eye, and the primary cause is breast cancer. This is a retrospective analysis, which reports the clinical experience of eye metastases in 16 patients during the period of January, 1991, to December, 2002, who attended a tertiary referral center in Mexico City. Mean age at diagnosis was 40 yr (range 24-58). Most of patients were initially in clinical stage IIB-IV. Median time from breast cancer diagnosis to development of ocular metastases was 22.5 mo and from metastatic disease to ocular metastases was 10 mo. Ocular symptoms were decrease of visual acuity, ocular pain, nonspecific symptoms, proptosis, and palpebral edema. Three patients had bilateral ocular metastases. Fourteen patients were treated with radiation, and clinical response was documented in 4/15 eyes; ocular pain responded in three patients with this symptom. No ocular enucleations were performed. One patient developed glaucoma. No other major toxicities were documented. Median survival time was 26 mo and 25% of our patients were alive at a maximum follow-up of 90 mo. This entity requires early recognition in order to preserve the visual function and quality of life of patients with breast cancer, since their prognosis has improved in recent years. more...

e11500 Background: Breast cancer in older women is usually undertreated, this population is considered fragile, they receive dose of chemotherapy below standards. The aim fo the study is to evaluat... more...

e11016 Background: Preclinical studies have shown that the combination of an aromatase inhibitor (AI) and oral fluoropyrimidines in estrogen receptor (ER)-positive cell lines enhance antitumor efficacy. This might be explained by reduction of ER-induced growth signaling in addition to decrease in estrogen production. This retrospective analysis of a cohort of patients with metastatic breast cancer (MBC) evaluates the efficacy and safety of combined AI with capecitabine. Methods: Patients with hormone receptor-positive MBC treated with this combination were evaluated and outcomes were compared to women treated with capecitabine (conventional dose) or AI as monotherapy. The administered total dose of capecitabine was 2000 mg. per day in combination with AI. Results: Of 93 patients evaluated, 37 received the combination treatment, 27 capecitabine and 29 an AI. Combination was used in 26 patients as first-line treatment and 11 as second-line. At the time of progression, 92% had a performance status of ≤2 and 58% of patients had visceral disease. No significant difference was observed between the three groups according to clinical and pathological features. Mean follow-up was 23 months (m). The median PFS of first-line treatment was significantly better for the combination (PFS not-reached vs.3.0 m for capecitabine and 13.0 m for AI, p more...

e12027 Background: Clinical experience and previous studies suggest that women with diabetes and breast cancer (BrCa) have worse outcomes than their non-diabetic counterparts. However, analysis of the contribution of diabetes to BrCa specific mortality is difficult because of the substantial mortality attributed to diabetes alone and because diabetes is commonly associated with adverse prognostic factors specific to BrCa. The purpose of this study was to examine the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent BrCa. Methods: We performed a retrospective analysis of patients with advanced BrCa receiving palliative chemotherapy from 2006 to 2011 at the National Cancer Institute in Mexico, and compared breast cancer-specific mortality in diabetic and non-diabetic patients, as well as in patients that presented hyperglycemia during palliative treatment. Results: A total of 265 patients receiving palliative therapy were eligible for inclusion. Previous diagnosis or detection of diabetes at recurrence was recorded in 40 patients (15%). No difference was observed between diabetic and non-diabetic patients in terms of overall survival (OS). A statistically significant difference in OS was observed between patients without diabetes and diabetics who had hyperglycemia (p=0.003). OS in diabetic patients with proper metabolic control was shown to be superior compared to diabetics with hyperglycemia (p=0.01). Hyperglycemia was identified in 14% of non-diabetics at some point while receiving palliative treatment. For patients that experienced hyperglycemia during treatment or who had a mean glucose level > 130, either in the diabetic or non-diabetic subgroups, a worse outcome was noted compared to normoglycemic patients, with a HR of 1.5 (p=0.029) and HR of 2.04 (p=0.006) for death, respectively. Conclusions: Elevated glucose levels confer a poor outcome in diabetic and non-diabetic patients in contrast with patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians must monitor glucose levels during treatment for advanced BrCa disease, and should take action in order to maintain normal glucose levels. more...

1607 Background: Mexico positions right up at the top with U.S. in worldwide rankings of the most obese countries. In addition, breast cancer (BrCa) is the main type of cancer among women in this country. Studies have shown inconsistent results regarding obesity as a prognostic factor for worse outcome. Methods: Our aim is to identify if overweight and obesity confer poor prognosis in non-metastasic BrCa patients (pts). We identified 1799 Hispanic women with newly diagnosed BrCa who attended the National Cancer Institute in Mexico from 2004-2008 and compared clinical and pathological features and overall survival (OS) between pts with a body mass index (BMI) > or ≤ than 25. Results: The median age at diagnosis was 51 years. A BMI>25 was found in 71% of pts. Postmenopausal women comprised 52%, and had a greater proportion of cases with a BMI>25 than premenopausal pts (75% vs. 67%, p25 presented with more advanced TNM stages and nodal involvement than their counterparts (73% vs. 67%, p=0.005 and 76% vs. 71%, p=0.017; respectively). Overall prevalence of hormone-receptor (HR), triple-negative (TN) and HER2 positive disease was 62%, 23%, and 27%, respectively. Differences according to receptor status between pre and postmenopausal pts and BMI are shown in table. There was no difference in disease-free survival and OS according to overweight and obesity in the overall population, but when menopausal status was considered, premenopausal pts with BMI>25 had a worse OS compared to pts with BMI more...

11063 Background: Despite broad advances in the treatment of LABC, 30 to 40% of patients responding to NACT develop locoregional relapse. We performed a retrospective analysis of the experience obtained so far in patients with LABC who were treated with CRT after NACT in terms of pathologic complete response (pCR), relapse-free survival (RFS) and overall survival (OS) at our institution. Methods: One hundred and twelve patients with LABC (Stage IIB-IIIB) were treated between January 2000 and December 2003 with NACT with 5FU 500mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500mg/m2 (FAC) or doxorubicin 50 mg/m2 and cyclophosphamide 500mg/m2 (AC) administered i.v. in four 21-day cycles. CRT with 60 Gy whole-breast irradiation and concurrent weekly mitomycin 5mg, 5FU 500mg and dexamethasone 16 mg or cisplatin 30 mg, gemcitabine 100 mg and dexamethasone 16 mg. Subsequently they underwent surgery and 6 to 8 weeks later received 2 additional courses of FAC, AC or paclitaxel 90mg weekly for 12 weeks and in estrogen receptor (ER) positive patients hormone therapy. Results: Median tumor size 5 cm; stages IIB, IIIA and IIIB were 21.4%, 42.9% and 35.7% respectively. pCR was 42% (CI 95% 33.2 - 50.5) in breast and 29.5% (CI 95% 21.4 - 37.5) in breast and axillary lymph nodes. Multivariate analysis showed the main determinant of pCR was negative ER (P 0.016). Median RFS has not been reached. The 5 year RFS is 76.9% (CI 95% 68.2 - 84.7). No relationship between pCR and RFS was found. Multivariate analysis showed the main determinant of RFS was the clinical stage (p=0.03). Only one patient had local recurrence. The 5 year OS is 84.2% (CI 95% 75 - 93.2). Toxicity during CRT: grade 1–2 neutropenia 32.2%, grade 1–2 anemia 5.2%, grade 3 radioepithelitis 22.4% Conclusions: This modality has good locoregional control for locally advanced breast cancer with an acceptable toxicity profile. Futher investigation of concurrent chemoradiotherapy should be explored in LABC. No significant financial relationships to disclose. more...

906 Background: Breast cancer in patients with ten or more positive lymph nodes, constitutes a big problem concerning adjuvant treatment. Till now many modalities have been utilized to manage this patients, without good results and very high costs. The objective of our study was to explore if a reinduction chemotherapy might provide longer survival for this group of patients. Methods: Pilot prospective study including patients that remained disease free, with ten and more positive axillary lymph nodes, after two years of finishing adjuvant chemo-radiotherapy. They received one cycle of chemotherapy every two years approximately. Since a prolonged survival was observed, they were compared with historical controls receiving the same neoadjuvant and/or adjuvant treatment, matching the cases in age, stage and positive lymph nodes, alive and disease free at 30 months. Statistical analysis was performed with ttest and X2 for group similarity. Kaplan Meier method was used to analyse survival and logrank test for... more...