The somatic mutation profile of estrogen receptor-positive HER2-negative metastatic breast cancer in Brazilian patients.

Background: Breast cancer is the leading cause of cancer death among women worldwide. Studies about the genomic landscape of metastatic breast cancer (MBC) have predominantly originated from developed nations. There are still limited data on the molecular epidemiology of MBC in low- and middle-income countries. This study aims to evaluate the prevalence of mutations in the PI3K-AKT pathway and other actionable drivers in estrogen receptor (ER)+/HER2- MBC among Brazilian patients treated at a large institution representative of the nation's demographic diversity. Methods: We conducted a retrospective observational study using laboratory data (OC Precision Medicine). Our study included tumor samples from patients with ER+/HER2- MBC who underwent routine tumor testing from 2020 to 2023 and originated from several Brazilian centers within the Oncoclinicas network. Two distinct next-generation sequencing (NGS) assays were used: GS Focus (23 genes, covering PIK3CA, AKT1, ESR1, ERBB2, BRCA1, BRCA2, PALB2, TP53, but not PTEN) or GS 180 (180 genes, including PTEN, tumor mutation burden [TMB] and microsatellite instability [MSI]). Results: Evaluation of tumor samples from 328 patients was undertaken, mostly (75.6%) with GS Focus. Of these, 69% were primary tumors, while 31% were metastatic lesions. The prevalence of mutations in the PI3K-AKT pathway was 39.3% (95% confidence interval, 33% to 43%), distributed as 37.5% in PIK3CA and 1.8% in AKT1. Stratification by age revealed a higher incidence of mutations in this pathway among patients over 50 (44.5% vs 29.1%, p=0.01). Among the PIK3CA mutations, 78% were canonical (included in the alpelisib companion diagnostic non-NGS test), while the remaining 22% were characterized as non-canonical mutations (identifiable only by NGS test). ESR1 mutations were detected in 6.1%, exhibiting a higher frequency in metastatic samples (15.1% vs 1.3%, p=0.003). Additionally, mutations in BRCA1, BRCA2, or PALB2 were identified in 3.9% of cases, while mutations in ERBB2 were found in 2.1%. No PTEN mutations were detected, nor were TMB high or MSI cases. Conclusion: We describe the genomic landscape of Brazilian patients with ER+/HER2- MBC, in which the somatic mutation profile is comparable to what is described in the literature globally. These data are important for developing precision medicine strategies in this scenario, as well as for health systems management and research initiatives.

Implications of tumor-infiltrating lymphocytes in early-stage triple-negative breast cancer: clinical oncologist perspectives.

Breast cancer (BC) is the most common neoplasm in women worldwide and one of the leading causes of female death. The triple-negative subtype, characterized by the absence of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2), tends to occur in younger patients, be more aggressive and less differentiated. Furthermore, this subtype is considered the most immunogenic and associated with higher levels of tumor cell infiltration, mainly lymphocytes. Tumor-infiltrating lymphocytes (TILs) play a crucial role in the interaction of the host's immune system and cancer cells. The microenvironment is critical in tumor development and progression. Assessment of infiltrating lymphocytes can provide valuable information about the immune response and, given the lack of biomarkers to guide treatment decisions and predict outcomes in triple-negative tumors and can be considered as a potential biomarker. Some evidence suggests that higher levels of these lymphocytes are associated with better responses to systemic treatment, longer progression-free survival and overall survival (OS). However, treatment escalation or de-escalation strategies for triple-negative BC (TNBC) currently do not consider the presence or density of TILs for therapeutic decisions. TILs appear to be useful predictive and prognostic indicators. Further clinical studies are needed to confirm these relationships and integrate TILs as a biomarker consistently into clinical practice. This article summarizes key concepts relating to the role of the immune infiltrate in BC, along with the current status and future prospects regarding TILs as a predictive and prognostic biomarker.

Metachronous breast neoplasms: squamous cell carcinoma and lobular carcinoma in situ within a fibroadenoma

Breast squamous cell carcinoma are rare, occurring in less than 0.1% of all breast carcinomas. This report describes the oncological conduct performed on a patient with a triple negative squamous cell carcinoma in the upper outer quadrant of the right breast. The same patient presented a lobular carcinoma in situ within a fibroadenoma of the contralateral breast, during the follow up period. The association of these two diseases in the same patient has not yet been described in the literature.

Reconstrução mamária em paciente com complexo aréolo-papilar supranumerário / Breast reconstruction in patient with supernumerary nipple-areola complex

Numerosas técnicas de reconstrução mamária são utilizadas como alternativas para pacientes submetidas à mastectomia. Uma das fases desse processo é a confecção cirúrgica do complexo aréolo-papilar (CAP), seguida de tatuagem para criação de nova aréola. Este relato descreve a conduta cirúrgica realizada em uma paciente com carcinoma ductal invasivo (triplo negativo), localizado na junção dos quadrantes superiores (JQS) da mama direita, na qual foi utilizado retalho cutâneo caudal contendo um CAP supranumerário na cobertura da reconstrução mamária que incluiu músculo grande dorsal e expansor tecidual.

Numerous breast reconstruction techniques are used as alternatives to patients submitted to mastectomy. One of the stages to breast reconstruction is surgical confection of nipple-papillary complex followed by tattooing to create a new areola. This report describes the surgical treatment in a patient with invasive ductal carcinoma (triple-negative), located at the junction of the upper quadrants of the right breast; where was utilized caudal cutaneous flap, containing a supernumerary nipple-papillary complex; in the coverage of breast reconstruction that included the latissimus dorsi flap and tissue expander.

O impacto da biópsia do linfonodo sentinela na qualidade de vida de mulheres submetidas à cirurgia conservadora de mama / Impact of sentinel lymph node biopsy in quality of life of women submitted to breast conservative surgery

Objetivo: Comparar técnicas de setorectomia somada à biópsia de linfonodo sentinela (SBLS) e de setorectomia somada à linfadenectomia axilar total (SLAT) quanto ao impacto na qualidade de vida (QV) de pacientes com câncer de mama (CM). Métodos: Estudo transversal comparando QV entre pacientes submetidas a diferentes técnicas de cirurgia conservadora de mama, em Chapecó, mediante aplicação de Questionário de Qualidade de Vida para Pacientes Mastectomizadas (QQVPM), elaborado pela Organização Europeia para a Pesquisa e Tratamento do Câncer (EORTC). Participaram da pesquisa pacientes diagnosticadas com carcinoma de mama submetidas à cirurgia conservadora entre os anos de 2004 e 2009, divididas em grupo caso (bi- ópsia de linfonodo sentinela) e grupo controle (linfadenectomia axilar total), com 49 pacientes em cada grupo. Resultados: A média de escores de QV foi: linfonodo sentinela=6,32; linfadenectomia=5,35; as médias de escores em cada domínio foram: imagem corporal (linfonodo sentinela=3,92; linfadenectomia=3,82), medo de recorrência (linfonodo sentinela=3,15; linfadenectomia=3,00), satisfação com o tratamento (linfonodo sentinela=1,22; linfadenectomia=1,46), resultados estéticos (linfonodo sentinela=2,14; linfadenectomia=2,85). Conclusões: Pacientes submetidas à setorectomia somada à biópsia de linfonodo sentinela referiram melhores escores de QV; também proporcionando menor medo de recorrência. Pacientes mais idosas apresentaram melhor percepção da imagem corporal, menor medo de recorrência da doença e sentiram-se mais satisfeitas com o tratamento. A QV foi afetada negativamente pelo maior defeito cirúrgico (tamanho do espécime excisado) e pela localização central da lesão primária mamária.

Objective: To compare setorectomia techniques coupled with sentinel lymph node biopsy and setorectomia added to the total axillary lymphadenectomy about the impact on quality of life of patients with breast cancer. Methods: Cross-sectional study comparing quality of life among patients undergoing different techniques of conservative breast surgery, in Chapecó, through application of Quality of Life Questionnaire for mastectomy patients, prepared by the European Organization for Research and Treatment of Cancer. The participants were patients diagnosed with breast carcinoma underwent conservative surgery between the years 2004 and 2009, divided into case group (sentinel node biopsy) and control group (axillary lymphadenectomy total), with 49 patients in each group. Results: The mean scores of quality of life was (sentinel lymph node=6,32; lymphadenectomy=5,35), the mean scores of each domain were: body image (sentinel lymph node=3,92; lymphadenectomy=3,82), fear of recurrence (sentinel lymph node=3,15; lymphadenectomy=3,00), satisfaction with treatment (sentinel lymph node=1,22; lymphadenectomy=1,46), aesthetic results (sentinel lymph node=2,14; lymphadenectomy=2,85). Conclusions: Patients undergoing setorectomia coupled with sentinel lymph node biopsy related better quality of life scores, which also caused less fear of recurrence. Older patients have better perception of their body image; have less fear of recurrence and feel more satisfied with treatment. Quality of life was affected negatively by the greater weight of the excised specimen and the location of the tumor in the center of the breast.