Real-World Experience in Hispanic Patients With Breast Cancer and Brain Metastases Using Different Prognostic Tools.

PURPOSE: Only a small percentage of Hispanic patients have been included in studies that developed prognostic models for breast cancer and brain metastases. Therefore, there is a clear need for tools tailored to this demographic. This study assesses the efficacy of common prognostic tools in a Hispanic population. METHODS AND MATERIALS: We retrospectively analyzed a data set of Hispanic patients with breast cancer and newly diagnosed brain metastases from 2009 to 2023 at a single referral center. For each prognostic tool, Kaplan-Meier curves were built. The performances of the models were compared using the area under the curve (AUC), C-statistic, and Akaike information criteria (AIC). RESULTS: Of 492 patients, the median time from breast cancer to brain metastasis diagnosis was 22.7 months (IQR, 12.1-53.3). The median overall survival was 11.6 months (95% CI, 9.9-13.4). All models were validated as prognostic tools (P < .001). The model with the better performance was the breast graded prognostic assessment (GPA; AIC, 402; AUC, 0.65), followed by the modified GPA (AIC, 406; AUC, 0.64), the disease-specific GPA (AIC, 407; AUC, 0.62), recursive partitioning analysis (AIC, 421; AUC, 0.62), and GPA (AIC, 422; AUC, 0.60). CONCLUSIONS: The breast GPA demonstrated superior accuracy in prognosticating outcomes for Hispanic patients with breast cancer and brain metastases. This underscores the critical importance of incorporating racial and ethnic diversity in creating and validating medical prognostic tools.

Capecitabine Plus Aromatase Inhibitor as First Line Therapy for Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer.

(1) Background: recent evidence suggests that long low-dose capecitabine regimens have a synergistic effect with endocrine therapy as aromatase inhibitors (AIs), and might increase overall survival for hormone-receptor-positive, HER2-negative, metastatic breast cancer compared to both treatments. We performed a retrospective study to confirm the efficacy and expand the safety data for capecitabine plus AI (a combination henceforth named XELIA) for this indication. (2) We conducted a single-center retrospective cohort study of 163 hormone receptor-positive metastatic breast cancer patients who received either the XELIA regimen, capecitabine, or an aromatase inhibitor (AI) as single agents in first-line treatment. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival, best objective response, and toxicity incidence. (3) Results: the median progression-free survival for patients receiving XELIA, AI, and capecitabine was 29.37 months (20.91 to 37.84; 95% CI), 20.04 months (7.29 to 32.80; 95% CI) and 10.48 (8.69 to 12.28; 95% CI), respectively. The overall response rate was higher in the XELIA group (29.5%) than in the AI (14.3%) and capecitabine (9.1%) groups. However, the differences in overall survival were not statistically significant. Apart from hand-foot syndrome, there were no statistically significant differences in adverse events between the groups. (4) Conclusions: this retrospective study suggests that progression-free survival and overall response rates improved with the XELIA regimen compared to use of aromatase inhibitors and capecitabine alone. Combined use demonstrated an adequate safety profile and might represent an advantageous treatment in places where CDK 4/6 is not available. Larger studies and randomized clinical trials are required to confirm the effects shown in our study.

Pathogenic variant profile in DNA damage response genes correlates with metastatic breast cancer progression-free survival in a Mexican-mestizo population.

Introduction: Metastatic 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. Methods: We sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing. Results: Overall, 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. Discussion: Our 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.

Prognosis of breast cancer diagnosed during pregnancy and early postpartum according to immunohistochemical subtype: A matched case-control study.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.05). CONCLUSION: Patients diagnosed during pregnancy and early postpartum are at high risk of recurrence. Further research is warranted to better characterize PABC tumor biology and enable the identification of novel therapeutic interventions to improve treatment outcomes.

Identification of risk factors for central nervous system metastasis in patients with breast cancer with neurologic symptoms.

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 <50 years at the time of BC diagnosis (odds ratio [OR], 2.5; 95% confidence interval [95% CI], 1.8-3.5 [P < .0001]), human epidermal growth factor receptor 2 (HER2)-positive status (HER2+) (OR, 3.6; 95% CI, 2.1-6.1 [P < .0001]), luminal B/HER2+ subtype (OR, 3.1; 95% CI, 1.9-5.3 [P < .001]), triple-negative subtype(OR, 2.4; 95% CI, 1.5-4 [P = .001]), and Karnofsky performance status ≤70 (OR, 6.6; 95% CI, 4.5-9.6 [P < .0001]) were associated with a higher frequency of CNSm. Brain parenchyma was the most common site of CNSm. The median overall survival after a diagnosis of CNSm was 12.2 months (95% CI, 9.3-15.1 months). CONCLUSIONS: CNSm is not uncommon among patients with BC, particularly in those with neurologic symptoms who require neuro-oncology evaluation and are aged <50 years at the time of diagnosis, have HER2+ or triple-negative subtypes, have a poor Karnofsky performance status, and/or have ≥2 non-CNS metastases.

Prognostic Value of the Pretreatment Neutrophil-to-Lymphocyte Ratio in Different Phenotypes of Locally Advanced Breast Cancer During Neoadjuvant Systemic Treatment.

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.

Real-World Outcomes Among Older Mexican Women with Breast Cancer Treated with Neoadjuvant Chemotherapy.

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 <65 years. Disease-free survival and overall survival were compared between groups according to pathologic complete response and subtype, defined by hormone receptor and human epidermal growth receptor 2 (HER2) status. 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.

miRNA profile obtained by next­generation sequencing in metastatic breast cancer patients is able to predict the response to systemic treatments.

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 early­stage BC develop metastasis within 5 years. The management of MBC consists of systemic therapy. Despite different treatment options, the 5­year survival rate is <20%, which may be due to a lack of response with de novo or acquired resistance. MicroRNAs (miRNAs or miRs) are promising biomarkers as they are readily detectable and have a broad spectrum and potential clinical applications. The aim of this study was to identify a miRNA profile for distinguishing patients with MBC who respond to systemic treatment. Patients with MBC were treated according to the National Comprehensive Cancer Network guidelines. We performed miRNA­Seq on 9 primary tumors using the Thermo Fisher Scientific Ion S5 system. To obtain global miRNA profiles, we carried out differentially expressed gene elimination strategy (DEGES) analysis between the responsive and non­responsive patients. The results identified a profile of 12 miRNAs associated with the response to systemic treatment. The data were validated in an independent cohort (TCGA database). Based on the results, the upregulation of miR­342­3p and miR­187­3p was associated with the response to systemic treatment, and with an increased progression­free survival (PFS) and overall survival (OS); by contrast, the downregulation of miR­301a­3p was associated with a higher PFS and OS. On the whole, the findings of this study indicate that these miRNAs may serve as biomarkers for the response to systemic treatment or the prognosis of patients with MBC. However, these data should be validated experimentally in other robust cohorts and using different specimens before implementing these miRNAs as biomarkers in clinical practice to benefit this group of patients.

Effects of omega-3 fatty acids supplementation on neoadjuvant chemotherapyinduced toxicity in patients with locally advanced breast cancer: a randomized, controlled, double-blinded clinical trial / Efecto de la suplementación con ácidos grasos omega-3 sobre la toxicidad secundaria a quimioterapia neoadyuvante en pacientes con cáncer de mama localmente avanzado: ensayo clínico aleatorizado

Background: 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

Introducción: uno de los tratamientos para el cáncer 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 ácidos grasos poliinsaturados omega 3 (AGPI Ω-3), ya que modulan negativamente algunas vías moleculares como las que inducen la activación del factor nuclear-kappa B (NF-κB), involucrado con los mecanismos de toxicidad secundaria a la administración de antraciclinas. Objetivo: valorar el efecto de los AGPI n-3, sobre la toxicidad de la QTneo, la composición corporal, el perfil cardiometabólico y la calidad de vida en mujeres con CMLA durante la QTNeo. Métodos: se incluyeron cincuenta y tres mujeres con CMLA, en un estudio clínico doble ciego controlado con placebo. Las pacientes recibieron aleatoriamente 2,4 g/día 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 terminología común para eventos adversos (CTCAE, versión 4.03) y la escala Global subjetiva del Sistema de Evaluación de los Síntomas de Edmonton (ESAS), la composición corporal y la toxicidad cardiometabólica. Resultados: no hubo diferencias significativas entre los grupos en los parámetros de toxicidad hematológica y antropométricos. La xerostomía de la escala de Edmonton, presento una mejora significativa (p = 0,032) en los pacientes suplementados con AGPI Ω-3. Conclusión: la suplementación con AGPI Ω-3 no mostró cambios en la composición corporal ni en la toxicidad del tratamiento neoadyuvante, solamente se encontró una mejoría significativa en la xerostomía

Effects of omega-3 fatty acids supplementation on neoadjuvant chemotherapy-induced toxicity in patients with locally advanced breast cancer: a randomized, controlled, double-blinded clinical trial.

INTRODUCTION: Background: 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.

INTRODUCCIÓN: Introducción: uno de los tratamientos para el cáncer 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 ácidos grasos poliinsaturados omega 3 (AGPI Ω-3), ya que modulan negativamente algunas vías moleculares como las que inducen la activación del factor nuclear-kappa B (NF-κB), involucrado con los mecanismos de toxicidad secundaria a la administración de antraciclinas. Objetivo: valorar el efecto de los AGPI n-3, sobre la toxicidad de la QTneo, la composición corporal, el perfil cardiometabólico y la calidad de vida en mujeres con CMLA durante la QTNeo. Métodos: se incluyeron cincuenta y tres mujeres con CMLA, en un estudio clínico doble ciego controlado con placebo. Las pacientes recibieron aleatoriamente 2,4 g/día 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 terminología común para eventos adversos (CTCAE, versión 4.03) y la escala Global subjetiva del Sistema de Evaluación de los Síntomas de Edmonton (ESAS), la composición corporal y la toxicidad cardiometabólica. Resultados: no hubo diferencias significativas entre los grupos en los parámetros de toxicidad hematológica y antropométricos. La xerostomía de la escala de Edmonton, presento una mejora significativa (p = 0,032) en los pacientes suplementados con AGPI Ω-3. Conclusión: la suplementación con AGPI Ω-3 no mostró cambios en la composición corporal ni en la toxicidad del tratamiento neoadyuvante, solamente se encontró una mejoría significativa en la xerostomía.

[Prognostic factors in patients with breast cancer and brain metastasis as the first site of recurrence]. / Factores pronósticos en pacientes con cáncer de mama y metástasis cerebral como primer sitio de recurrencia.

OBJECTIVE: To evaluate the prognostic factors (clinicalpathological characteristics and treatments) in patients with breast cancer and metastasis to central nervous system (CNS) as the first site of the disease. MATERIAL AND METHODS: Kaplan-Meier method and life tables were used to estimate overall survival time over a retrospective cohort of 125 breast cancer patients treated at the Instituto Nacional de Cancerología (INCan) during 2007-2015, who presented metastasis to the CNS as the first site of extension of the disease. The cox proportional hazards model was used to determine the prognosis factors. RESULTS: The median overall survival time was 14.2 months (IC95%: 11.83-26.93). Patients with triple negative (TN), according to inmunohistochemistry analysis classification, had lower survival times (p=0.0004) and had a risk of dying two times (p=0.037) higher than patients with a different immunophenotype (HR: 2.77. 95%CI: 1.10-6.99). The degree of intermediate SBR increases the risk of dying in patients with metastasis (HR 2.76, 95% CI: 1.17-6.51). CONCLUSIONS: CNS metastasis continues to be a poor prognostic factor that reduces survival and affects quality of life. It is recommended to monitor the early presence of clinical neurological manifestations during follow-up for prompt treatment. TN patients have worse prognosis and HER2+ a better control.

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<0.004) y con dos veces más riesgo de fallecer, en comparación con los otros inmunofenotipos (HR= 2.77; IC95% 1.10-6.99); asimismo, se identificó que un grado intermedio en la escala Scarff-Bloom-Richardson incrementa el riesgo de morir en pacientes con metástasis (HR=2.76; IC95% 1.17-6.51). CONCLUSIONES: La metástasis al SNC continúa siendo un factor de mal pronóstico que reduce la supervivencia y afecta la calidad de vida. Se recomienda vigilar puntualmente la presencia de manifestaciones clínicas neurológicas durante el seguimiento, para una rápida intervención. Las pacientes TN tienen peor pronóstico, y las HER2+ (es decir, con resultado positivo para el receptor 2 del factor de crecimiento humano epidérmico), mejor control a mediano plazo.

Clinical characteristics and outcomes of older women with breast cancer in Mexico.

INTRODUCTION: 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. MATERIALS AND METHODS: 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 aged <65 and ≥65 years of age. Survival analyses were performed for each molecular subtype. RESULTS: 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. CONCLUSIONS: 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.

Factores pronósticos en pacientes con cáncer de mama y metástasis cerebral como primer sitio de recurrencia / Prognostic factors in patients with breast cáncer and brain metastasis as the first site of recurrence

Resumen: 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<0.004) y con dos veces más riesgo de fallecer, en comparación con los otros inmunofenotipos (HR= 2.77; IC95% 1.10-6.99); asimismo, se identificó que un grado intermedio en la escala Scarff-Bloom-Richardson incrementa el riesgo de morir en pacientes con metástasis (HR=2.76; IC95% 1.17-6.51). Conclusiones: La metástasis al SNC continúa siendo un factor de mal pronóstico que reduce la supervivencia y afecta la calidad de vida. Se recomienda vigilar puntualmente la presencia de manifestaciones clínicas neurológicas durante el seguimiento, para una rápida intervención. Las pacientes TN tienen peor pronóstico, y las HER2+ (es decir, con resultado positivo para el receptor 2 del factor de crecimiento humano epidérmico), mejor control a mediano plazo.

Abstract: Objective: To evaluate the prognostic factors (clinical-pathological characteristics and treatments) in patients with breast cancer and metastasis to central nervous system (CNS) as the first site of the disease. Materials and methods: Kaplan-Meier method and life tables were used to estimate overall survival time over a retrospective cohort of 125 breast cancer patients treated at the Instituto Nacional de Cancerología (INCan) during 2007-2015, who presented metastasis to the CNS as the first site of extension of the disease. The cox proportional hazards model was used to determine the prognosis factors. Result: The median overall survival time was 14.2 months (IC95%: 11.83-26.93). Patients with triple negative (TN), according to inmunohistochemistry analysis classification, had lower survival times (p=0.0004) and had a risk of dying two times (p=0.037) higher than patients with a different immunophenotype (HR: 2.77. 95%CI: 1.10-6.99). The degree of intermediate SBR increases the risk of dying in patients with metastasis (HR 2.76, 95% CI: 1.17-6.51). Conclusion: CNS metastasis continues to be a poor prognostic factor that reduces survival and affects quality of life. It is recommended to monitor the early presence of clinical neurological manifestations during follow-up for prompt treatment. TN patients have worse prognosis and HER2+ a better control.

Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy.

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).

Clinical and Epidemiological Profile of Breast Cancer in Mexico: Results of the Seguro Popular.

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.

A microRNA signature associated with pathological complete response to novel neoadjuvant therapy regimen in triple-negative breast cancer.

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 < 0.05). The differential expression of miR-30a, miR-9-3p, miR-770, and miR-143-5p was validated in an independent group of 17 patients with or without pathological complete response. Moreover, Kaplan-Meier analysis showed that expression of these four microRNAs was associated with an increased disease-free survival. Gene ontology classification of predicted microRNA targets indicated that numerous genes are involved in pathways related to chemoresistance, such as vascular endothelial growth factor, focal adhesion kinase, WNT, ERbB, phosphoinositide 3-kinase, and AKT signaling. In summary, we identified a novel microRNA expression signature associated with pathological complete response in breast cancer. We propose that the four validated microRNAs could be used as molecular biomarkers of clinical response in triple-negative breast cancer patients with pathological complete response to neoadjuvant therapy.

Molecular Subtypes and Prognosis in Young Mexican Women With Breast Cancer.

INTRODUCTION: 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. PATIENTS AND METHODS: 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 and > 40 years of age. Survival analyses were performed for each molecular subtype. RESULTS: 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). CONCLUSION: 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.

Real-world outcomes in young women with breast cancer treated with neoadjuvant chemotherapy.

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.

Outcomes of Hispanic women with lymph-node positive, HER2 positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab in Mexico.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Thalidomide combined with neoadjuvant chemotherapy in angiosarcoma of the breast with complete pathologic response: case report and review of literature.

BACKGROUND: Primary angiosarcoma of the breast is a rare malignancy. CASE REPORT: We report on a 41-year-old female patient who initially presented with locally advanced disease. Core biopsy showed angiosarcoma of the breast, grade 1, CD31-positive. The patient was treated with neoadjuvant systemic chemotherapy based on cisplatin, doxorubicin, and paclitaxel, given concurrently with thalidomide. After treatment completion, the patient underwent radical mastectomy. Pathologic complete response in the breast and axillary lymph nodes was achieved. The patient has no evidence of disease recurrence 6 months after her initial diagnosis. CONCLUSION: Anti-angiogenic therapy may be considered as part of the management of primary angiosarcoma of the breast.