Real-World Evidence of Ribociclib Plus Aromatase Inhibitors as First-Line Treatment in Advanced Breast Cancer: The BrasiLEEira Study.

PURPOSE: Cyclin inhibitors plus endocrine therapy represent the reference standard for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer (ABC). Efficacy results on hard end points such as overall survival come from well-designed randomized clinical trials (RCTs). However, a limitation of RCTs is the low external results validity, and their extrapolation to a broader population may not be appropriate. Real-world studies can overcome these limitations, also increasing the reliability of RCTs. MATERIALS AND METHODS: The BrasiLEEira was an observational, longitudinal, retrospective, multicenter study to evaluate the effectiveness and safety of ribociclib plus nonsteroidal aromatase inhibitors in Brazilian women age 18 years or older with HR+/HER2- ABC. The study was approved by the institutional review boards of all 11 hospitals. Data were collected anonymously from medical records using an electronic case report form designed by an independent academic research organization, which conducted the study considering all recommendations of international guidelines. The primary end point was 1-year progression-free survival (PFS) rate. Secondary end points included mortality, dose reduction, and safety. RESULTS: The mean age of 76 patients was 57 years, and 28.9% were Black/Brown. The most prevalent comorbidity was arterial hypertension (34.7%). About 26.0% had endocrine-resistant disease, and 54.1% had more than three metastatic sites. The PFS rate was 77.6%. Three patients died (3.9%). Dose reductions occurred in 37.7% of patients. The most common adverse event was neutropenia (68.4%). CONCLUSION: The high-quality evidence from the BrasiLEEira study corroborates the RCTs' findings, expanding its validity to a broader spectrum and underrepresented population who may benefit from ribociclib treatment.

Management of patients with recurrent/metastatic endometrial cancer: Consensus recommendations from an expert panel from Brazil.

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.

Exercise volume load in women with breast cancer: Study protocol for the ABRACE randomized clinical trial.

Background: An increased number of breast cancer patients are challenged by acute and persistent treatment side effects. Oncology guidelines have been establishing physical exercise to counteract several treatment-related toxicities throughout cancer care. However, evidence regarding the optimal dose-response, feasibility, and the minimal resistance exercise volume and/or intensity remains unclear. The ABRACE Study will assess the impact of different resistance training volumes (i.e., single or multiple sets) combined with aerobic exercise on physical and psychological outcomes of breast cancer patients undergoing primary treatment. Methods: This study is a randomized, controlled, three-armed parallel trial. A total of 84 participants, aged ≥18 years, with breast cancer stages I-III, initiating adjuvant or neoadjuvant chemotherapy (≤50% of sessions completed) will be randomized to multiple sets resistance training plus aerobic training group, single set resistance training plus aerobic training group or control group. Neuromuscular and cancer-related fatigue (primary outcomes), muscle strength, muscle thickness, muscle quality by echo intensity, body composition, cardiorespiratory capacity, functional performance, upper-body endurance and quality of life will be measured before and after the 12-week intervention. Our analysis will follow the intention-to-treat approach and per-protocol criteria, with additional sub-group analysis. Discussion: Findings support prescribing exercise during chemotherapy for breast cancer and elucidate the potential role of different resistance training volumes as a management strategy for physical and psychological impairments in women with early-stage breast cancer. Our main hypothesis is for superiority in physical and psychological outcomes for both training groups compared to the control group, with no difference between single or multiple sets groups. Trial registration: Clinical trials NCT03314168.

The impact of sociodemographic factors and health insurance coverage in the diagnosis and clinicopathological characteristics of breast cancer in Brazil: AMAZONA III study (GBECAM 0115).

PURPOSE: In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients' characteristics at diagnosis and their association with health insurance type. METHODS: This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured. RESULTS: A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II-III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p < .0001) than public, whereas Luminal B HER2-positive (19.2% vs. 14.2%, p = 0.0012) and HER2-positive (8.8% vs. 5.1%, p = 0.0009) were more common in patients with public health system coverage. Only 34% of patients were diagnosed by screening exams. Privately insured patients were more frequently diagnosed with stage I disease when compared to publicly insured patients; publicly insured patients had more stage III (33.5% vs. 14.7%; p-value < 0.0001) disease than privately insured ones. Breast cancer was detected by symptoms more frequently in publicly than in privately insured patients (74.2% vs 25.8%, respectively; p-value < 0.0001). CONCLUSIONS: Patients with public health coverage were diagnosed with symptomatic disease, later stages and more aggressive subtypes when compared to privately insured patients.

Advanced Stage at Diagnosis and Worse Clinicopathologic Features in Young Women with Breast Cancer in Brazil: A Subanalysis of the AMAZONA III Study (GBECAM 0115).

PURPOSE: Breast cancer (BC) in young women is uncommon and tends to present with more aggressive characteristics. To better understand and characterize this scenario in Brazil through real-world data, we performed a subanalysis of AMAZONA III study (ClinicalTrials.gov identifier: NCT02663973). METHODS: The AMAZONA III study (GBECAM 0115) is a prospective registry that included 2,950 women newly diagnosed with invasive BC in Brazil from January 2016 until March 2018 at 22 sites. Valid data were obtained from 2,888 patients regarding age at diagnosis and complete baseline information. To compare epidemiologic and clinicopathological features at the time of diagnosis, patients with BC were divided into two groups according to age: ≤ 40 years and > 40 years. Quantitative variables were described as means, and categorical variables were described as frequencies and percentages and compared using the Pearson's χ2 test. RESULTS: Of 2,888 women diagnosed with BC, 486 (17%) were ≤ 40 years old. Young women had higher educational level, most were employed and a significant number were married (P < .001 for all associations). Younger patients were more symptomatic at BC diagnosis (P < .001), and they also presented more frequently with stage III, T3/T4, grade 3 tumors, HER-2-positive, luminal B, and triple-negative subtypes. CONCLUSION: Brazilian women younger than age 40 years have unfavorable clinicopathological features of BC at diagnosis, with more aggressive subtypes and advanced stage when compared with older women. These differences are not explained by socioeconomic or ethnic imbalances. The causes of a higher prevalence of BC among young women in Brazil deserve additional investigation.

Clinical and genetic characterization of basal cell carcinoma and breast cancer in a single patient.

INTRODUCTION: Multiple environmental and genetic factors are involved with the development of basal cell carcinomas (BCC), as well as with breast cancers. Tumor initiation and progression are often associated with genomic instability such as aneuploidies, and gains or losses of large chromosomal segments, known as copy number alterations (CNAs). CNAs have been successfully detected using the microarray comparative genomic hybridization technique (array-CGH) at high resolution. Data thus obtained are useful to identify specific genomic aberrations, to classify tumor stages, and to stratify subgroups of patients with different prognosis and clinical behaviors. CASE DESCRIPTION: Clinical study of a 66-year-old white female identified two primary tumors, a ductal invasive grade-II carcinoma of the breast, and one nodular BCC. Germline and tumor genomic survey utilized the 180 K array-CGH analysis to investigate chromosomal alterations. DISCUSSION AND EVALUATION: Several chromosomal anomalies were detected in the breast tumor genome, including focal ~422 Kb 13q13.3 microdeletion. In the BCC, amplification of a chromosome 6 spanning the centromere region between the cytobands 6p23 and 6q12 was identified. Several 6p amplified genes correspond to families of histone and human leukocyte antigen genes, whereas some of the CNAs found in the breast tumor are uncommon. No germline CNA was detected in the normal skin of the patient at this technical resolution. CONCLUSION: CNAs found in the two different tumors of the patient constitute independent events arisen in the somatic lineage. Relevant genes to both carcinogenesis and progression are to be affected by these CNAs.

Idade como fator prognóstico no câncer de mama em estádio inicial / Edad como factor pronóstico en el cáncer de mama en fase inicial / Age as a prognostic factor in early breast cancer

OBJETIVO: Analisar a idade como fator prognóstico no câncer de mama em estádio clínico inicial. MÉTODOS: Estudo retrospectivo que analisou as características clínicas e a sobrevida livre de doença de 280 pacientes entre 25 e 81 anos com câncer de mama estágio clínico I e II com acompanhamento em hospital de Porto Alegre (RS), de 1995 a 2000. Dados clínicos, patológicos, tratamento e desfechos foram extraídos dos prontuários das pacientes. As pacientes foram divididas em dois grupos conforme a idade ao diagnóstico (<40 anos e >40 anos). Os dois grupos foram comparados quanto ao estágio clínico, histologia, expressão de receptores hormonais, terapia e radioterapia utilizando o teste qui-quadrado e/ou exato de Fisher e para análise de sobrevida, o teste de long-rank e método de Kaplan-Meier. RESULTADOS: Do total de 280 mulheres estudadas, 54 (19,3 por cento) tinham até 40 anos de idade. Ambos os grupos de pacientes eram similares em estágio clínico, histologia e expressão de receptores hormonais. A proporção de pacientes com sobrevida livre de doença em seguimento de 56 meses foi significativamente maior nas pacientes acima de 40 anos (84 por cento versus 70 por cento). Proporcionalmente, as pacientes mais jovens receberam mais terapia adjuvante (88,8 por cento versus 77,8 por cento). Houve diferença significativa na probabilidade das mulheres acima de 40 anos de permanecerem livre de doença (84 por cento), sendo mais evidente quando comparadas às pacientes com < 40 anos em estágio clínico I. CONCLUSÕES: Os achados confirmam que mulheres de até 40 anos com câncer de mama inicial apresentam um pior prognóstico. Entretanto, tal prognóstico parece não estar relacionado a maior número de casos com receptores hormonais negativos. Pacientes jovens que permaneceram livre de doença receberam mais terapia adjuvante, sugerindo efeito positivo da quimioterapia e hormonioterapia.

OBJECTIVE: To analyze age as a prognostic factor in early breast cancer. METHODS: Retrospective study analyzing the clinical profile and disease-free survival in a group of 280 subjects aged 25 to 81 years with stage I and II breast cancer followed-up in Porto Alegre, southern Brazil, from 1995 to 2000. Clinical, pathological, treatment and outcome data were obtained from medical records. Subjects were divided into two groups according to age at diagnosis (<40 years and >40 years). The two groups were compared for clinical stage, histology, hormone receptor expression, therapy and radiotherapy using the chi-square and/or Fisher's exact test and for analysis of survival the Kaplan-Meier method with a long-rank test. RESULTS: Of 280 women studied, 54 (19.3 percent) were younger than 40 years. Both groups were similar regarding clinical stage, histology, and hormone receptor expression. The proportion of subjects with disease-free survival in the 56-month follow-up was significantly higher in those over 40 years (84 percent versus 70 percent). Proportionally, younger subjects received more adjuvant therapy (88.8 percent vs. 77.8 percent). Those women over 40 years were significantly more likely to remain disease-free (84 percent), and this difference was more remarkable when they were compared to those over 40 years at stage I breast cancer. CONCLUSIONS: The study findings confirm that women younger than 40 years with early breast cancer have a poorer prognosis. However, this prognosis does not seem to be related to increased number of hormone receptor-negative cases. Younger patients who remained disease-free received more adjuvant therapy, suggesting a positive effect of chemotherapy and endocrine therapy.

OBJETIVO: Analizar la edad como factor pronóstico en el cáncer de mama en fase clínico inicial. MÉTODOS: Estudio retrospectivo que analizó las características clínicas y la sobrevida libre de enfermedad de 280 pacientes entre 25 y 81 años con cáncer de mama fase clínica I y II con acompañamiento en hospital de Porto Alegre (Sur de Brasil), de 1995 a 2000. Datos clínicos, patológicos, tratamiento y resultados fueron extraídos de los prontuarios de las pacientes. Las pacientes fueron divididas en dos grupos conforme la edad al diagnóstico (<40 anos y >40 anos). Los dos grupos fueron comparados con relación a la fase clínica, histología, expresión de receptores hormonales, terapia y radioterapia utilizando la prueba chi-cuadrado y/o exacto de Fisher y para análisis de sobrevida, la prueba de long-rank y método de Kaplan-Meier. RESULTADOS: Del total de 280 mujeres estudiadas, 54 (19,3 por ciento) tenían hasta 40 años de edad. Ambos grupos de pacientes eran similares en fase clínica, histología y expresión de receptores hormonales. La proporción de pacientes con sobrevida libre de enfermedad en seguimiento de 56 meses fue significativamente mayor en las pacientes mayores de 40 años (84 por ciento vs. 70 por ciento). Proporcionalmente, las pacientes más jóvenes recibieron más terapia adyuvante (88,8 por ciento vs. 77,8 por ciento). Hubo diferencia significativa en la probabilidad de las mujeres mayores de 40 años de permanecer libre de enfermedad (84 por ciento), siendo más evidente cuando se compararon con las pacientes con < 40 años en fase clínica I. CONCLUSIONES: Los resultados confirman que mujeres de hasta 40 años con cáncer de mama inicial presentan un peor pronóstico. Sin embargo, tal pronóstico parece no estar relacionado con el mayor número de casos con receptores hormonales negativos. Pacientes jóvenes que permanecieron libres de enfermedad recibieron más terapia adyuvante, sugiriendo efecto positivo de la quimioterapia y hormonaterapia.

[Age as a prognostic factor in early breast cancer]. / Idade como fator prognóstico no câncer de mama em estádio inicial.

OBJECTIVE: To analyze age as a prognostic factor in early breast cancer. METHODS: Retrospective study analyzing the clinical profile and disease-free survival in a group of 280 subjects aged 25 to 81 years with stage I and II breast cancer followed-up in Porto Alegre, southern Brazil, from 1995 to 2000. Clinical, pathological, treatment and outcome data were obtained from medical records. Subjects were divided into two groups according to age at diagnosis (< or = 40 years and > 40 years). The two groups were compared for clinical stage, histology, hormone receptor expression, therapy and radiotherapy using the chi-square and/or Fisher's exact test and for analysis of survival the Kaplan-Meier method with a long-rank test. RESULTS: Of 280 women studied, 54 (19.3%) were younger than 40 years. Both groups were similar regarding clinical stage, histology, and hormone receptor expression. The proportion of subjects with disease-free survival in the 56-month follow-up was significantly higher in those over 40 years (84% versus 70%). Proportionally, younger subjects received more adjuvant therapy (88.8% vs. 77.8%). Those women over 40 years were significantly more likely to remain disease-free (84%), and this difference was more remarkable when they were compared to those over 40 years at stage I breast cancer. CONCLUSIONS: The study findings confirm that women younger than 40 years with early breast cancer have a poorer prognosis. However, this prognosis does not seem to be related to increased number of hormone receptor-negative cases. Younger patients who remained disease-free received more adjuvant therapy, suggesting a positive effect of chemotherapy and endocrine therapy.

Câncer de mama em mulheres jovens / Breast neoplasms in young women

Os autores fazem uma revisão bibliográfica sobre o câncer de mama em mulheres com menos de 35 anos de idade, considerada uma doença de manifestação precoce nesta faixa etária. Abordaremos o diagnóstico, as opções terapêuticas e as implicações da doença na vida destas pacientes