Race, Gene Expression Signatures, and Clinical Outcomes of Patients with High-Risk Early Breast Cancer

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. Design, Setting, and Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure: Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. Main Outcomes and Measures: The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. Results: The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P =.87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P =.01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P =.007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P =.01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P =.008). A transforming growth factor β signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. Conclusions and Relevance: The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.. © 2023 American Medical Association. All rights reserved.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Cerebral mass lesion due to cytomegalovirus in a patient with AIDS: case report and literature review Lesão expansiva cerebral devida a citomegalovírus: relato de caso e revisão da literatura

Cytomegalovirus (CMV) disease in acquired immunodeficiency syndrome (AIDS) patients most commonly presents as chorioretinitis and gastro-intestinal infection. Neurological involvement due to CMV may cause several clinical presentations: polyradiculitis, myelitis, encephalitis, ventriculo-encephalitis, and mononeuritis multiplex. Rarely, cerebral mass lesion is described. We report a 39 year-old woman with AIDS and previous cerebral toxoplasmosis. She presented with fever, seizures, and vulval ulcers. Her chest X-ray showed multiple lung nodules, and a large frontal lobe lesion was seen in a brain computed tomography scan. She underwent a brain biopsy through a frontal craniotomy, but her condition deteriorated and she died in the first postoperative day. Histopathological studies and immunohistochemistry disclosed CMV disease, and there was no evidence of cerebral toxoplasmosis, bacterial, mycobacterial or fungal infection. CMV disease should be considered in the differential diagnosis of cerebral mass lesion in AIDS patients. High suspicion index, timely diagnostic procedures (surgical or minimally invasive), and proper utilization of prophylactic and therapeutic medication could improve outcome of these patients.<br>As doenças causadas pelo citomegalovírus (CMV) em pacientes com a síndrome da imunodeficiência adquirida apresentam-se principalmente como corioretinite ou comprometimento gastrointestinal. No sistema nervoso central, o CMV pode causar diversas síndromes clínicas: poliradiculite, mielite, encefalite, ventrículo-encefalite e mononeurite múltipla. Raramente, lesões expansivas cerebrais são descritas. Os autores relatam o caso de uma paciente de 39 anos com antecedentes de infecção pelo HIV e toxoplasmose cerebral, que apresentou-se com febre, convulsões e úlceras vulvares. O raios-X de tórax demonstrou múltiplos nódulos pulmonares e a tomografia computadorizada de crânio evidenciou extensa lesão no lobo frontal esquerdo. Após ser submetida à craniotomia, evoluiu com piora clínica, falecendo no primeiro dia de pós-operatório. Os estudos histopatológicos e imunohistoquímicos demonstraram doença citomegálica. Foram excluídas toxoplasmose cerebral e infecção bacteriana, micobacteriana ou fúngica. Concluímos que, embora seja extremamente raro, o CMV deve ser considerado no diagnóstico diferencial das lesões expansivas cerebrais em pacientes com infecção pelo HIV. Um elevado índice de suspeita, procedimentos diagnósticos oportunos (cirúrgicos ou minimamente invasivos), e o adequado uso de antivirais (terapêuticos e profiláticos) podem melhorar o prognóstico desta letal manifestação