Prevalencia de subtipos de cáncer de mama y su asociación con factores reproductivos / Prevalence of breast cancer subtypes and their association with reproductive factors

Introducción: Los factores reproductivos se asocian con cáncer de mama. Actualmente se estudia el comportamiento según subtipos moleculares. Objetivo: Establecer la prevalencia de estos subtipos y su asociación con factores reproductivos en mujeres atendidas en centros del nororiente colombiano. Método: Estudio observacional de corte transversal, en mujeres con cáncer de mama subtipos luminales y HER2 durante 2012-2021. Se indagaron variables sociodemográficas, factores reproductivos y estadio tumoral. Resultados: En total, 347 pacientes cumplieron criterios de elegibilidad, correspondiendo a luminal A el 49,8% (intervalo de confianza del 95% [IC95%]: 44,5-55,1), a luminal B el 29,1% (IC95%: 24,3-33,9) y a HER2 el 15,5% (IC95%: 11,7-19,4). Las mujeres con tumores de mama luminal B tenían más riesgo de tener estadios localmente avanzados (odds ratio [OR]: 1,83; IC95%: 1,11-3,01; p = 0,02). Agrupando los subtipos luminales frente a HER2 se encontró que el 40,72% de las pacientes con subtipos luminales no habían lactado, frente al 69,71% con HER2 (diferencia estadísticamente significativa a favor de luminal A; OR: 1,91; IC95%: 1,02-3,53; p = 0,041). Conclusiones: La prevalencia de tumores luminales es del 84,5%. Existe asociación diferencial entre el antecedente de lactancia materna y la aparición de subtipos luminales, es decir, las mujeres que no lactaron se corresponden con mayor frecuencia con HER2. No se estableció asociación con otros factores estudiados.

Introduction: Stimulus-estrogenic factors are associated with breast cancer. Currently, the behavior according to molecular subtypes is being studied. Objective: To establish the prevalence of these subtypes and their association with reproductive factors in women attended in centers in northeastern Colombia. Method: Observational cross-sectional study in women with breast cancer subtypes luminal and HER2 during 2012 -2021. Sociodemographic variables, stimulus-estrogenic factors and tumor stage were investigated. Results: In total, 347 patients met eligibility criteria, corresponding to luminal A 49.8% (95% confidence interval [95%CI]: 44.5-55.1), luminal B 29.1% (95%CI: 24.3-33.9) and HER2 15.5% (95%CI: 11.7-19.4). Women with luminal B breast tumors were at higher risk of having locally advanced stages (odds ratio [OR]: 1.83; 95%CI: 1.11-3.01; p = 0.02). Grouping the luminal subtypes versus HER2 showed that 40.72% of patients with luminal subtypes had not lactated, compared to 69.71% HER2 (statistically significant difference in favor of luminal A; OR: 1.91; 95%CI: 1.02-3.53; p = 0.041). Conclusions: The prevalence of luminal tumors is 84.5%. There is a differential association between the history of breastfeeding and the appearance of luminal subtypes, i.e., women who did not breastfeed are more likely to have HER2. No association was established with other factors studied.

Relevancia y prevalencia de los parámetros histopatológicos y subtipos moleculares del cáncer de mama en mujeres del área costera de Ecuador atendidas en una institución de Salud Pública / Prevalence and significance of breast cancer pathologycal subtypes in Ecuador

BACKGROUND: The success of breast cancer (BC) treatment depends largely on the clinical-histological characteristics of the patient. Immunohistochemical (IHC) Breast Cancer Subtypes are crucial for therapeutic purposes. AIM: To determine the relevance and prevalence of the histopathological parameters and molecular subtypes of BC among women attending public health services. MATERIAL AND METHODS: A retrospective cross-sectional study was carried out in 199 female patients with histopathological diagnosis of breast cancer, treated at a Guayaquil city hospital in Ecuador, from January 2014 to December 2017. RESULTS: Luminal A carcinoma was the most prevalent tumor in the studied women (54%). Thirty seven percent of patients did not have nodal involvement, 40% had one to three lymph nodes involved and 2% had 10 or more nodes involved. Most patients had a tumor size > 2 and ≤ 5 cm (72%) and moderately differentiated specifications (57%). CONCLUSIONS: The study allowed the characterization of breast cancer according to the prevalence of molecular subtypes and clinical and histological characteristics. These factors determine therapeutic behaviors that optimize the use of the limited resources of the Public Health System.

A multicenter study of the clinicopathological characteristics and a risk prediction model of early-stage breast cancer with hormone receptor-positive/human epidermal growth factor receptor 2-low expression / 中华医学杂志(英文版)

BACKGROUND@#In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model.@*METHODS@#Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors.@*RESULTS@#In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%.@*CONCLUSION@#Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events.@*REGISTRITATION@#ChiCTR.org.cn, ChiCTR2100046766.

Consensus on the clinical use of CDK4/6 inhibitors for the treatment of hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer (2023 edition) / 中华肿瘤杂志

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have led transformative breakthrough of clinical therapy for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative breast cancer patients. CDK4/6 inhibitors that have been marketed in China include Ribociclib, Palbociclib, Abemaciclib and Dalpiciclib. For HR-positive HER-2-negative locally advanced and metastatic breast cancer, CDK4/6 inhibitors combined with endocrine therapy have become standard regimen, which can prolong the survival of patients. In the adjuvant treatment stage of early breast cancer, CDK4/6 inhibitors have also achieved positive results and been approved for indications. At present, CDK4/6 inhibitors have been widely used in clinical practice in China. In order to further improve the standardized application of CDK4/6 inhibitors in China, the Breast Cancer Expert Committee of the National Center for Cancer Quality Control and the Professional Committee of Clinical Research of Cancer Drugs of the Chinese Anti-Cancer Association organized the related expert to update the consensus based on the "CDK4/6 inhibitor consensus on clinical application of in the treatment of hormone receptor positive human epidermal growth factor receptor 2 negative advanced breast cancer (2021 edition)" . The updated consensus systematically introduces the pharmacological characteristics, drug monitoring and adverse event management, etc., of CDK4/6 inhibitors to promote the accuracy of clinical decision-making with the ultimate goal to prolong the overall survival of patients and improve the quality of life.

Chinese expert consensus on multigene testing for adjuvant treatment of HR-positive, HER-2 negative early breast cancer(2023 edition) / 中华肿瘤杂志

Breast cancer is the most common malignant tumor in women, of which the majority is early breast cancer (EBC). The strategy of postoperative adjuvant treatment relies mainly on the clinicopathologic characteristics of patients, but there are certain deficiencies if only depending on it to assess treatment benefits and disease prognosis. Multigene testing tools can evaluate the prognosis and predict therapeutic effects of breast cancer patients to guide the clinical decision-making on whether to use adjuvant chemotherapy, radiotherapy, and endocrine therapy by detecting the expression levels of specific genes. The consensus-writing expert group, based on the characteristics, validation results, and accessibility of the multigene testing tools and combined with clinical practice, described the result interpretation and clinical application of OncotypeDx(®) (21-gene), Mammaprint(®) (70-gene), RecurIndex(®) (28-gene), EndoPredict(®)(12-gene), and BreastCancerIndex(®) (BCI, 7-gene) for hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC. The development and validation process of each tool was also briefly introduced. It is expected that the consensus will help guide and standardize the clinical use of multigene testing tools and further improve the level of precise treatment for EBC.

Efficacy and clinical outcome of chemotherapy and endocrine therapy as first-line treatment in patients with hormone receptor-positive HER2-negative metastatic breast cancer / 中华医学杂志(英文版)

BACKGROUND@#Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC.@*METHODS@#Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed.@*RESULTS@#Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS.@*CONCLUSIONS@#ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.

Advances in Diagnosis and Treatment of HER2-positive Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.
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Treatment of palbociclib in hormone receptor positive breast cancer: a real-world study and efficacy prediction model / 中华肿瘤杂志

Objective: To summarize the clinical use of palbociclib and evaluate its efficacy and safety in hormone-receptor (HR)-positive advanced breast cancer patients. Methods: We retrospectively analyzed data from 66 HR-positive metastatic breast cancer patients treated with palbociclib and endocrine therapy at the Department of Oncology in the First Affiliated Hospital with Nanjing Medical University between 2018 and 2020. We evaluated the factors affecting the efficacy of palbociclib using Kaplan-Meier method and Log-rank test for survival analysis and Cox regressions for multivariate analysis. Nomogram model was built for predicting prognosis among HR-positive breast cancer patients who received palbociclib. Concordance index (C-index) and calibration curve were used for internal validation to assess the predictive ability and conformity of the model. Results: Of the 66 patients treated with palbociclib, 33.3%(22), 42.4%(28) and 24.2%(16) patients were treated without endocrine therapy, first-line endocrine therapy, second-line or above endocrine therapy after recurrence, respectively. 36.4%(24) patients had hepatic metastasis, 16.7% (11) patients were sensitive to previous endocrine therapy, 27.3%(18/66) patients had primary resistance to endocrine therapy, while 56.1% (37) patients had secondary resistance to endocrine therapy. The overall response rate was 14.3% (95% CI: 6.7%, 25.4%) and clinical benefit rate was 58.7% (95% CI: 45.6%, 71.0%). Better clinical outcomes were associated with non-hepatic metastasis (P=0.001), sensitive/secondary resistant to previous endocrine therapy (P=0.004), no or only one line of chemotherapy for metastatic breast cancer (P=0.004), recent pathological confirmation of immunohistochemical analysis (P=0.025). Hepatic metastasis (P=0.005) and primary resistance to endocrine therapy (P=0.016) were the independent risk factors of progression free survival. The C-index of predictive probability for the nomogram constructed from the patient clinical characteristics (whether liver metastasis, whether primary endocrine resistance, lines of chemotherapy after metastasis, lines of endocrine therapy, number of metastatic sites, and time to last immunohistochemistry) to predict the progression-free survival at 6 and 12 months for patients was 69.7% and 72.1%, respectively. The most common adverse events were hematologic toxicities. Conclusions: Our report indicates that palbociclib combined with endocrine therapy for HR-positive recurrent metastatic breast cancer is effective and safe; patients with hepatic metastases and primary resistance to endocrine therapy have worse prognoses and are independent risk factors for progression after palbociclib therapy. The constructed nomogram could help predict the survival and guide the use of palbociclib.

Effects of adjuvant trastuzumab on long-term survival of T1N0M0 stage human epidermal growth factor receptor 2 positive breast cancer: a real-world study / 中华肿瘤杂志

Objective: To investigate the prognosis impact of adjuvant trastuzumab treatment on human epidermal growth factor receptor 2 (HER-2) positive early breast cancer patients. Methods: A retrospective study was conducted, HER-2-positive T1N0M0 stage breast cancer patients who underwent surgery in the Affiliated Tumor Hospital of Xinjiang Medical University from January 2010 to December 2019 were divided into treatment group and control group according to whether they were treated with trastuzumab or not. Propensity score matching (PSM) was used to balance the confounding bias caused by differences in baseline characteristics between the two groups. Cox proportional hazards model was used to analyze the risk factors affecting disease-free survival (DFS). The Kaplan-Meier method was used to estimate the 3- and 5-year DFS and overall survival (OS) rates of the two groups before and after PSM. Results: There were 291 patients with HER-2 positive T1N0M0 stage breast cancer, including 21 cases in T1a (7.2%), 61 cases in T1b (21.0%), and 209 cases in T1c (71.8%). Before PSM, there were 132 cases in the treatment group and 159 cases in the control group, the 5-year DFS rate was 88.5%, and the 5-year OS rate was 91.5%. After PSM, there were 103 cases in the treatment group and 103 cases in the control group, the 5-year DFS rate was 86.0%, and the 5-year OS rate was 88.5%. Before PSM, there were significant differences in tumor size, histological grade, vascular invasion, Ki-67 index, postoperative chemotherapy or not and radiotherapy between the treatment group and the control group (P<0.05). After PSM, there were no significant difference in clinicopathological features between the treatment group and the control group (P>0.05). Multivariate analysis showed that histological grade (HR=2.927, 95 CI: 1.476, 5.805; P=0.002), vascular invasion (HR=3.410, 95 CI: 1.170, 9.940; P=0.025), menstrual status (HR=3.692, 95 CI: 1.021, 13.344, P=0.046), and chemotherapy (HR=0.238, 95 CI: 0.079, 0.720; P=0.011) were independent factors affecting DFS. After PSM, the 5-year DFS rate of the treatment group was 89.2%, while that of the control group was 83.5%(P=0.237). The 5-year OS rate of the treatment group was 96.1%, while that of the control group was 84.7%(P=0.036). Conclusion: Postoperative targeted therapy with trastuzumab can reduce the risk of recurrence and metastasis in patients with HER-2-positive T1N0M0 stage breast cancer.

Use of artificial intelligence to predict response to neoadjuvant chemotherapy in breast cancer

:Breast cancer is the object of thousands of studies worldwide. Nevertheless, few tools are available to corroborate prediction of response to neoadjuvant chemotherapy. Artificial intelligence is being researched for its potential utility in several fields of knowledge, including oncology. The development of a standardized Artificial intelligence-based predictive model for patients with breast cancer may help make clinical management more personalized and effective. We aimed to apply Artificial intelligence models to predict the response to neoadjuvant chemotherapy based solely on clinical and pathological data. Methods: Medical records of 130 patients treated with neoadjuvant chemotherapy were reviewed and divided into two groups: 90 samples to train the network and 40 samples to perform prospective testingand validate the results obtained by the Artificial intelligence method. Results: Using clinicopathologic data alone, the artificial neural network was able to correctly predict pathologic complete response in 83.3% of the cases. It also correctly predicted 95.6% of locoregional recurrence, as well as correctly determined whether patients were alive or dead at a given time point in 90% of the time. To date, no published research has used clinicopathologic data to predict the response to neoadjuvant chemotherapy in patients with breast cancer, thus highlighting the importance of the present study. Conclusions: Artificial neural network may become an interesting tool for predicting response to neoadjuvant chemotherapy, locoregional recurrence, systemic disease progression, and survival in patients with breast cancer (AU)

Using the analytic hierarchy process to elicit patient preference in the evaluation of first-line treatment of HER2-overexpressing metastatic breast cancer / Uso do processo analítico hierárquico para eleger a preferência do paciente na avaliação da primeira linha de tratamento do câncer de mama metastático her2 hiperexpresso

Abstract Background The many combinations of chemotherapeutic agents and biologicals available in the Brazilian National Health System for the treatment of metastatic breast cancer require analysis that contribute to decision making. Objective The study's primary aim was to evaluate the first-line treatment of HER2- overexpressing metastatic breast cancer from the Brazilian Unified Health System perspective using multicriteria decision analysis (MCDA). Method The treatment options evaluated were (a) pertuzumab combined with trastuzumab and docetaxel, and (b) trastuzumab in combination with docetaxel. Using the hierarchical analytical method, medical oncologists compared the relevance of five predefined criteria: overall survival, response to treatment, adverse events, cost- effectiveness, and budget impact. Results The therapeutic scheme considered more appropriate by the model was pertuzumab combined with trastuzumab and docetaxel. The most sensitive criteria were adverse events, cost-effectiveness, and budget impact. The results suggest that the classification has a close relationship with the perspective of healthcare professionals participating in the questionnaire. Conclusion Defining the treatment of an incurable disease associated with a short survival time and high-cost treatment options necessitates complex decision-making. MCDA allows the weighting of criteria and considering criteria that would be difficult to measure in other methods, such as cost-effectiveness. These aspects differ from economic models and contribute to a broader evaluation of health decision-making.

Resumo Introdução As diversas combinações de agentes quimioterápicos e biológicos disponíveis no Sistema Único de Saúde brasileiro para o tratamento do câncer de mama metastático requerem análises que contribuam para a tomada de decisões. Objetivo O objetivo principal deste estudo foi avaliar o tratamento de primeira linha para câncer de mama metastático HER2 hiperexpresso sob a perspectiva do Sistema Único de Saúde, utilizando a análise de decisão multicritérios (MCDA). Método As opções de tratamento avaliadas foram: (a) pertuzumabe em combinação com trastuzumabe e docetaxel, e (b) trastuzumabe em combinação com docetaxel. Usando o método analítico hierárquico, médicos oncologistas compararam a relevância dos cinco critérios predefinidos: sobrevida global, resposta ao tratamento, eventos adversos, custo-efetividade e impacto orçamentário. Resultados O esquema terapêutico considerado mais apropriado pelo modelo foi pertuzumabe em combinação com trastuzumabe e docetaxel. Os critérios mais sensíveis foram eventos adversos, custo-efetividade e impacto orçamentário. Os resultados sugerem que a classificação está associada à perspectiva do profissional de saúde participante do questionário. Conclusão Definir o tratamento de uma doença incurável associada a um tempo de sobrevida curto e opções de tratamento de alto custo requer uma tomada de decisão complexa. O MCDA permite ponderar e considerar critérios que seriam difíceis de medir em outros modelos de decisão. Esses aspectos contribuem para uma avaliação mais ampla da tomada de decisões em saúde.

Indicaciones para el uso de pertuzumab en cáncer de mama HER2 positivono metastásico en los escenarios neoadyuvante y adyuvante. Revisión de la evidencia y abordaje terapéutico en el Instituto Nacional de Cancerología - Colombia / Indications for the use of pertuzumab in non-metastatic HER2-positive breast cancer in the neoadjuvant and adjuvant. Review of the literature and therapeutic approach at the Instituto Nacional de Cancerología - Colombia

La adición de la terapia dirigida a la quimioterapia citotóxica en pacientes con cáncer de mama ha mejorado significativamente los desenlaces oncológicos en las pacientes con tumores HER2 positivo. El uso de pertuzumab durante el manejo neoadyuvante incrementa significativamente la respuesta patológica completa y en la actualidad permite emplear regímenes libres de antraciclinas con una eficacia similar y menores efectos cardiovasculares (en especial sobre la fracción de eyección). El beneficio en supervivencia libre de enfermedad invasiva, de adicionar pertuzumab en el escenario adyuvante en las pacientes sin tratamiento anti HER2 previo, está limitado a aquellas con ganglios positivos. La implementación de esquemas con bloqueo dual anti HER2, durante el tratamiento inicial del cáncer de mama HER2 positivo, mejora significativamente el pronóstico oncológico en este grupo de pacientes.

The addition of targeted therapy to cytotoxic chemotherapy in patients with breast cancer has significantly improved oncologic outcomes in patients with HER2-positive tumors. The use of pertuzumab during neoadjuvant management significantly increases the complete pathological response and currently allows the use of anthracycline-free regimens with similar efficacy and fewer cardiovascular effects (especially on ejection fraction). The benefit of pertuzumab in disease-free survival in the adjuvant setting for patients without prior anti-HER2 treatment is limited to those with positive nodes. The implementation of schemes with dual anti-HER2 blockade during the initial treatment of HER2-positive breast cancer significantly improves the oncological outcomes in this group of patients.

Análisis de la coexpresión de HER2/GRB7 y su asociación con variables clinicopatológicas en un grupo de mujeres colombianas con diagnóstico de cáncer de mama invasivo / Analysis of HER2/GRB7 co-expression and its association with clinicopathological variables in a group of Colombian women diagnosed with invasive breast cancer

Objetivo. Analizar las diferencias en la presentación de variables clínico-patológicas, de acuerdo con la expresión proteica de GRB7, en tumores HER2 positivos en mujeres colombianas con cáncer de mama invasivo, diagnosticado entre los años 2013 y 2015 en el Instituto Nacional de Cancerología E.S.E (INC). Métodos. Se incluyeron 158 pacientes con diagnóstico confirmado de cáncer de mama ductal invasivo. Se evaluó la expresión de los receptores hormonales (receptor de estrógeno (RE) y de progesterona (RP)), HER2, Ki67 y GRB7, mediante inmunohistoquímica (IHQ), y a partir de estos, se clasificaron los tumores en subtipos intrínsecos. Los análisis estadísticos incluyeron las pruebas de Chi-cuadrado/test exacto de Fisher para las variables categóricas, y la prueba U Mann Whitney/ Kruskal Wallis para las variables cuantitativas. Se evaluó la supervivencia global (SG) y libre de enfermedad (SLR) según la coexpresión de HER2/GRB7 usando el método de Kaplan-Meier y el test de log-rank. Resultados. La expresión de GRB7 se observó exclusivamente en tumores HER2-positivos (luminal B/HER2+ y HER2-enriquecidos: p<0,001). Los casos HER2+/GRB7+ mostraron una mayor expresión de Ki67 (40% vs. 27,5%, p=0,029), pero una tendencia a presentar un menor tamaño tumoral (30 mm vs. 51 mm, p=0,097), comparado con los tumores HER2+/GRB7-. No obstante, no se observaron diferencias en la supervivencia según la coexpresión de HER2/GRB7 (SG: p=0,6; SLR: p=0,07). Conclusiones. En nuestra muestra de estudio, la expresión de GRB7 en tumores HER2+ no se asoció con características clínico-patológicas de pronóstico desfavorable.

Objective: To analyze differences in the presentation of clinicopathological variables according to GRB7 protein expression in HER2-positive tumors in Colombian patients with invasive ductal breast carcinomas diagnosed between 2013 and 2015 at the Instituto Nacional de Cancerología (Bogotá, Colombia).Methods: A total of 158 breast cancer patients were included with a confirmed diagnosis of invasive ductal carcinoma. A single pathologist evaluated the protein expression of hormone receptors (estrogen (ER) and progesterone receptor (PR)), HER2, Ki67, and GRB7 by immunohistochemistry (IHC). The chi-square and Fisher's exact tests were used to assess differences between categorical variables, as well as the Mann-Whitney/Kruskal-Wallis U test for numerical variables. Overall (OS) and disease-free (DFS) survival were evaluated according to HER2/GRB7 co-expression using the Kaplan-Meier method and log-rank test.Results:GRB7 expression was observed exclusively in HER2-positive tumors (luminal B/HER2+ and HER2-enriched: p<0.001). HER2+/GRB7+ cases showed higher Ki67 expression (40% vs. 27.5%, p=0.029) and a tendency to present a smaller tumor (30 mm vs. 51 mm, p=0.097) compared to HER2+/GRB7- tumors. However, no differences in OS or DFS were observed by HER2/GRB7 co-expression (OS: p=0.6; DFS: p=0.07).Conclusions:Our results in Colombian patients indicate that GRB7 expression in HER2-positive breast tumors is not associated with unfavorable clinicopathological features.

Predictores histopatológicos de respuesta a tratamiento en pacientes con cáncer de mama receptores hormonales positivos her2 negativo. Un estudio de centro único / Histopathological predictors of response to treat-ment in patients with hormone receptor positive her2 negative breast cancer. A single center study

In troducción: Una de cada 18 mujeres desarrolla a lo largo de su vida cáncer de mama, siendo esta la principal causa de muerte por cáncer en mujeres.El propósito del presente estudio fue establecer el valor predictivo de los factores histopatológicos presentes en tumores malignos de mama con recepto-res hormonales positivos Her2 negativo de un grupo de pacientes en un centro de referencia oncológico.Met odología: Este estudio longitudinal se realizó en el Instituto Oncológico Nacional "Dr Juan TancaMa-rengo", de Guayaquil -Ecuador. El período de inclusión del 2007 al 2009 con período de observación hasta diciembre del 2020. Con una muestra no probabilística, se incluyeron mujeres con cáncer de mama, hormonal positivo Her2Neu negativo, que hayan recibido tratamiento adyuvante durante un pe-riodo de seguimiento. Se midieron variables demográficas, clínicas, relacionadas al tumor, clasificación TNM y sobrevida.Se realiza un análisis univariado descriptivo de la muestra, un análisis bivariado, com-parando el grupo de pacientes fallecidas con el grupo de pacientes vivas; un análisis de correlación entre variables en escala; un análisis de supervivencia y finalmente se presenta una regresión COX para pre-decir la supervivencia en base a las variables.R esultados: Ingresaron al estudio 105 pacientes, de 54.1 ± 11.4 años. 58.1% de casos en etapa temprana y 41.9% en etapa localmente avanzada. La sobrevida global (SG) fue de 67.6%a 14 añosy la sobrevida librede progresión (SLP) del 59.05%. La terapia de bloqueo hormonal se asoció con la SLP (R=0.544, P<0.01) y con SG (R=0.399, P<0.05). El compromiso ganglionar en estadio N0 tuvo una SLP de 11.9 ± 0.4 años, en estadio N3 fue de 6.8 ± 1.6 años (P<0.01). El modelo de regresión de Cox para predecir el tiempo de vida libre de progresión o enfermedad fue estadísticamente significativo con la terapia de bloqueo hormonal (R2=0.607, P<0.001) Conclusión: Laterapia de bloqueo hormonal mantenida por más de 5 años tiene un impacto positivo en la supervivencia de las pacientes con cáncer de mama hormonal positivo Her2 Neu negativo

In troduction:One in 18 women develops breast cancer throughout her life, this being the leading cause of death from cancer in women. The purpose of the present study was to establish the predictive value of the histopathological factors present in malignant breast tumors with positive hormone receptors Her2 negative in a group of patients in an oncology reference center.Met hodology: This longitudinal study was conducted at the "Dr. Juan Tanca Marengo" National Oncology Institute in Guayaquil -Ecuador. The inclusion period was from 2007 to 2009, with an observation period until December 2020. With a non-probabilistic sample, women with hormone-positive Her2 Neu negative breast cancer who had received adjuvant treatment during a follow-up period were included. Demo-graphic, clinical, tumor-related, TNM classification and survival variables were measured. A descriptive univariate analysis of the sample is performed, a bivariate analysis comparing the group of deceased patients with the group of living patients; a correlation analysis between variables in scale; a survival analysis; and a COX regression is presented to predict survival based on the variables.R esults: 105 patients,54.1 ± 11.4 years old, entered the study. 58.1% of cases are in the early stage, and 41.9% are in a locally advanced stage. Overall survival (OS) was 67.6% at 14 years, and progression-free survival (PFS) was 59.05%. Hormone blocking therapy was associated with PFS (R=0.544, P<0.01) and OS (R=0.399, P<0.05). Lymph node involvement in stage N0 had a PFS of 11.9 ± 0.4 years; stage N3 was 6.8 ± 1.6 years (P<0.01). The Cox regression model to predict progression-free or disease-free life was statistically significant with hormone blockade therapy (R2=0.607, P<0.001).C o nclusion: Hormone blockade therapy maintained for more than five years positively impacts the sur-vival of patients with hormone-positive Her2 Neu negative breast cancer.

Grado de infiltración linfocitaria tumoral al diagnóstico como factor pronóstico de recidiva en cánceres de mama de tipos moleculares rico en Her2 y triple negativo: Revisión Narrativa / Tumor infiltrating lymphocyte grade as prognostic factor of recurrence in molecular subtypes of breast cancer (triple negative and Her2): A narrative review

El carcinoma de mama es una enfermedad común, con efectos negativos significativos en la salud predominantemente femenina. Los linfocitos infiltrantes al tumor (TILs) son una manifestación de la respuesta inmune del huésped al cáncer. Este estudio revisa y resume los reportes bibliográficos relacionados con la eficacia pronóstica del porcentaje alto de TILs en cánceres de mama de tipos moleculares rico en HER2 y triple negativo. Se incluyeron estudios y revisiones en inglés buscados en la base de datos PubMed. Un mayor nivel de TILs se corresponde con mejor supervivencia libre de enfermedad tanto en los cánceres triple negativo como los ricos en HER2; por tanto, constituye un marcador histológico que debería ser utilizado rutinariamente en los análisis microscópicos de biop-sias de mama.

Breast cancer is a common disease affecting women, with significant health-related negative effects. Tumor-infiltrating lymphocytes (TILs) are recognized as manifestations of the host's antitumor im-munity. The following study reviews and summarizes reports on the effectiveness of prognosis of high levels of tumor-infiltrating lymphocytes on triple negative and HER2-enriched breast cancer molecular subtypes. Studies and reviews in English from Pubmed's database were included. A higher percentage of tumor- infiltrating lymphocytes is associated with better prognosis and survival rate of triple negative and HER2-enriched breast cancer. Consequently, such histological marker should be routinely used in the microscopic analysis of breast biopsies.

An easy and practical prognostic parameter: tumor-stroma ratio in Luminal, Her2, and triple-negative breast cancers

SUMMARY OBJECTIVE: The stroma surrounding the tumor cells is important in tumor progression and treatment resistance, besides the properties of tumor cells. Studies on the tumor stroma characteristics will contribute to the knowledge for new treatment approaches. METHODS: A total of 363 breast cancer patients were evaluated for the tumor-stroma ratio. The percentage of stroma was visually assessed on hematoxylin-eosin stained slides. The cases of tumor-stroma ratio more than 50% were categorized as tumor-stroma ratio high, and those less than 50% and below were categorized as tumor-stroma ratio low. RESULTS: Tumor-stroma ratio-high tumors had shorter overall survival (p=0.002). Disease-free survival tended to be shorter in tumor-stroma ratio-high tumors (p=0.082) compared with tumor-stroma ratio-low tumors. Tumor-stroma ratio was an independent prognostic parameter for the total group of patients (p=0.003) and also axillary lymph node metastasis and tumor-stroma ratio was statistically associated (p=0.004). Also, tumor-stroma ratio was an independent prognostic parameter in node-positive Luminal A and B subgroups for overall survival (p<0.001). CONCLUSION: Tumor-stroma ratio is an independent prognostic parameter that can be evaluated quite easily in all molecular subtypes of all breast cancers and does not require extra cost and time to evaluate.

A real world study on the relationship between drug resistance of targeted therapy and prognosis of HER-2-positive advanced breast cancer / 中华肿瘤杂志

Objective: To explore the effect of primary and acquired resistance to anti-human epidermal growth factor receptor 2 (HER-2) on the overall survival of patients with HER-2 positive advanced breast cancer. Methods: The clinical characteristics of HER-2 positive patients with advanced breast cancer admitted to Cancer Hospital of Chinese Academy of Medical Sciences from January 1998 to December 2018 were collected, and their neoadjuvant/adjuvant and advanced three-line chemotherapy were summarized. Among them, targeted drugs for HER-2 included trastuzumab, pertuzumab, T-DM1, RC48-ADC, lapatinib, pyrotinib, allitinib, sipatinib, seratinib. Based on the duration of benefit from anti HER-2 treatment, the patients were divided into two groups: primary anti HER-2 resistance group and acquired anti HER-2 resistance group. In this study, the overall survival (OS) was used as the main end point. Kaplan-Meier analysis and Cox proportional risk regression model were used to analyze the effects of different drug resistance mechanisms on the overall survival. Results: The whole group of 284 patients were included. The median age of recurrence and metastasis was 48 years old, 155 (54.6%) were hormone receptor (HR) positive and 129 (45.4%) were HR negative, 128 cases (45.1%) were premenopausal and 156 cases (54.9%) were postmenopausal, 277 cases (97.5%) had a score of 0-1 in ECoG PS and 7 cases (2.5%) had a score of more than 2 in the first diagnosis of relapse and metastasis. There were 103 cases (36.3%) in the primary drug resistance group and 181 cases (63.7%) in the secondary drug resistance group. The median overall survival time of the two groups was 24.9 months and 40.4 months, respectively, with statistical significance (P<0.001). Conclusion: Primary resistance to HER-2 is one of the factors of poor prognosis in HER-2 positive breast cancer, and its mechanism needs to be further explored.

Chinese expert consensus on multigene testing for postoperatively adjuvant treatment of hormone receptor-positive, HER2-negative early breast cancer / 中华肿瘤杂志

Breast cancer is the most common malignant tumor in women, of which early-stage (stages Ⅰ-Ⅱ) breast cancer (EBC) accounts for 73.1%. The strategy of postoperative adjuvant treatment relies mainly on the clinicopathologic characteristics of patients, but there are certain deficiencies in the assessment of treatment benefits and disease prognosis. Multigene testing tools can evaluate the prognosis and predict therapeutic effects of breast cancer patients to guide the clinical decision-making on whether to use adjuvant chemotherapy, radiotherapy, and endocrine therapy by detecting the expression levels of specific genes. The consensus-writing expert group, based on the characteristics, validation results, and accessibility of the multigene testing tools and combined with clinical practice, described the result interpretation and clinical application of OncotypeDx(®) (21-gene), MammaPrint(®) (70-gene), RecurIndex(®) (28-gene), and BreastCancerIndex(®) (BCI, 7-gene) for hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC. The development and validation process of each tool was also briefly introduced. It is expected that the consensus will help to guide and standardize the clinical application of multigene testing tools and further improve the level of precise treatment for EBC.

Searching for the emotional roots of breast cancer: A cross-disciplinary analysis integrating psychology, Chinese medicine, and oncology biomarkers / 中西医结合学报

OBJECTIVE@#We employed a multidisciplinary approach incorporating theoretical ideas, clinical experience, psychology, physiology, traditional Chinese medicine (CM), modern practice of CM, and oncology to explore the effect of patients' repression of negative emotions and traumatic events on breast cancer (BC) pathogenesis.@*METHODS@#BC female patients, older than 18 years of age, with available pathology reports who were treated at Rabin Medical Center were recruited. All participants completed questionnaires regarding medical history, behavioral tendencies, negative emotions, trauma, symptoms, and pathology (from a CM perspective). Data on tumor characteristics were collected from the pathology reports. The associations were examined using hierarchical binary logistic regressions.@*RESULTS@#A total of 155 BC patients were enrolled. The median age was 52 years, with a range of 26-79; 95% were mothers; 28% had estrogen receptor (ER)-negative BC, 52% had progesterone receptor (PR)-negative BC, 48% had human epidermal growth factor receptor 2-negative BC, and antigen Ki-67 ≥ 20% was reported for 52% of tumors. Statistically significant associations were found between the emotional markers (sense of motherhood failure, and lack of self-fulfillment), avoidance behavior, and physical symptoms that are related to emotional repression based on CM. Significant associations were also found between variables associated with physical symptoms of emotional repression, which involves the production and accumulation of non-substantial phlegm (i.e., "high-lipid Qi-like microscopic phlegm"), avoidance behavior which unconsciously uses "high-lipid Qi-like microscopic phlegm" in order to achieve emotional repression, and tumor parameters including tumor grade, PR status, and Ki-67. Patients with higher levels of "high-lipid Qi-like microscopic phlegm" were more likely to have tumors with worse prognosis (PR-negative, higher grade, and higher Ki-67).@*CONCLUSION@#We demonstrated a relationship between emotional parameters, behavioral tendencies, CM parameters, and oncologic parameters in BC. Additional research is warranted to explore these associations and their relevance to clinical practice.

Multicenter study of the clinicopathological features and recurrence risk prediction model of early-stage breast cancer with low-positive human epidermal growth factor receptor 2 expression in China (Chinese Society of Breast Surgery 021) / 中华医学杂志(英文版)

BACKGROUND@#: Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.@*METHODS@#: Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed.@*RESULTS@#: Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880).@*CONCLUSIONS@#: Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.@*TRIAL REGISTRATION@#: ChiCTR.org.cn, ChiCTR2100046766.