RESUMO
Immune checkpoint inhibition (ICI) with chemotherapy is now the standard of care for stage II-III triple-negative breast cancer; however, it is largely unknown for which patients ICI without chemotherapy could be an option and what the benefit of combination ICI could be. The adaptive BELLINI trial explored whether short combination ICI induces immune activation (primary end point, twofold increase in CD8+ T cells or IFNG), providing a rationale for neoadjuvant ICI without chemotherapy. Here, in window-of-opportunity cohorts A (4 weeks of anti-PD-1) and B (4 weeks of anti-PD-1 + anti-CTLA4), we observed immune activation in 53% (8 of 15) and 60% (9 of 15) of patients, respectively. High levels of tumor-infiltrating lymphocytes correlated with response. Single-cell RNA sequencing revealed that higher pretreatment tumor-reactive CD8+ T cells, follicular helper T cells and shorter distances between tumor and CD8+ T cells correlated with response. Higher levels of regulatory T cells after treatment were associated with nonresponse. Based on these data, we opened cohort C for patients with high levels of tumor-infiltrating lymphocytes (≥50%) who received 6 weeks of neoadjuvant anti-PD-1 + anti-CTLA4 followed by surgery (primary end point, pathological complete response). Overall, 53% (8 of 15) of patients had a major pathological response (<10% viable tumor) at resection, with 33% (5 of 15) having a pathological complete response. All cohorts met Simon's two-stage threshold for expansion to stage II. We observed grade ≥3 adverse events for 17% of patients and a high rate (57%) of immune-mediated endocrinopathies. In conclusion, neoadjuvant immunotherapy without chemotherapy demonstrates potential efficacy and warrants further investigation in patients with early triple-negative breast cancer. ClinicalTrials.gov registration: NCT03815890 .
RESUMO
BACKGROUND: A hibernoma is a rare benign lipomatous tumour, consisting of brown and white fat cells. In general, a hibernoma is an asymptomatic swelling that increases slowly in size, but it can sometimes cause pain. CASE DESPRIPTION: A 62-year-old woman presented at the breast clinic with a painful swelling in the right breast that was increasing in size. Radiological examination initially suggested a hamartoma. However, on the basis of histological examination of a biopsy, the diagnosis of hibernoma was made. The hibernoma was removed surgically. CONCLUSION: A hibernoma of the breast can grow to such a size that pain can arise due to compression of the mammary parenchyma. Surgical resection is only indicated if the hibernoma causes symptoms or for cosmetic reasons.
Assuntos
Neoplasias da Mama/diagnóstico , Lipoma/diagnóstico , Dor/etiologia , Biópsia , Neoplasias da Mama/complicações , Diagnóstico Diferencial , Feminino , Humanos , Lipoma/complicações , Pessoa de Meia-Idade , Dor/diagnósticoRESUMO
European Breast Cancer Council manifesto and supporting article on genetic risk prediction testing in breast cancer, presented at the 11th European Breast Cancer Conference in Barcelona, Spain.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Triagem e Testes Direto ao Consumidor , Detecção Precoce de Câncer , Testes Genéticos , Mutação , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Consenso , Feminino , Aconselhamento Genético , Predisposição Genética para Doença , Hereditariedade , Humanos , Terapia de Alvo Molecular , Linhagem , Fenótipo , Medicina de Precisão , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: The current debate on overdiagnosis and overtreatment of screen-detected ductal carcinoma in situ (DCIS) urges the need for prospective studies to address this issue. A substantial number of DCIS lesions will never form a health hazard, particularly if it concerns non- to slow-growing low-grade DCIS. The LORD study aims to evaluate the safety of active surveillance in women with low-risk DCIS. DESIGN: This is a randomised, international multicentre, open-label, phase III non-inferiority trial, led by the Dutch Breast Cancer Research Group (BOOG 2014-04) and the European Organization for Research and Treatment of Cancer (EORTC-BCG 1401). Standard treatment will be compared to active surveillance in 1240 women aged ⩾ 45 years with asymptomatic, screen-detected, pure low-grade DCIS based on vacuum-assisted biopsies of microcalcifications only. Both study arms will be monitored with annual digital mammography for a period of 10 years. The primary end-point is 10-year ipsilateral invasive breast cancer free percentage. Secondary end-points include patient reported outcomes, diagnostic biopsy rate during follow-up, ipsilateral mastectomy rate and translational research. FEASIBILITY: To explore interest in and feasibility of the LORD study we conducted a survey among EORTC and BOOG centres. A vast majority of EORTC and BOOG responding centres expressed interest in participation in the LORD study. The proposed study design is endorsed by nearly all centres.