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HER2-Low is defined as low levels of HER2 expression, based on a score of 1+ on immunohistochemical (IHC) assay or as an IHC score of 2+ and negative results on in situ hybridization (ISH or FISH). They are a heterogeneous population of breast cancers that vary in prognosis and sensitivity to systemic treatments. The frequency and clinical characteristics of pathogenic germline variants (PGVs) in HER2-Low breast cancer (BC) patients is not defined. We analyzed results from patients with BC who underwent multi-gene panel testing (MGPT) (maximum 145 genes) between 2018-2019. We reclassified HER-2 status accordingly. Relationships between the variables of interest were assessed by adopting the proportional regression Cox models. Of a total of 167 BC patients who underwent MGPT, half were hormone-receptor-positive. The median age was 45 years. About two thirds of the patients were in the earlier stage of BC. A total of 57% of the cases were reclassified as HER-2-negative or -Low. PGVs were found in 19% of the patients overall, as follows: seven BRCA1, four BRCA2, two ATM, one ATR, two CFTR, three CHEK2, one FANCA, one MERTK, one MLH1, three MUTYH, one RAD50, three RAD51C, one RECQL4, and two TP53 mutations. In HER2-Low, 26.5% of the patients had PGVs, and in the overall cohort, this was 19.8%. In conclusion, differences in the prevalence of deleterious germline mutations in HER2-Low BC patients compared to non-HER2-Low BC patients were identified. Similar alterations in BRCA were observed in this group of patients compared to the overall cohort. Germline genetic tests should be evaluated in larger cohorts of patients with HER2-Low status to better address the findings.
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OBJECTIVE: Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. METHODS: This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. RESULTS: A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. CONCLUSIONS: PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Estadificación de Neoplasias , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Inmunohistoquímica , Estimación de Kaplan-Meier , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Pronóstico , Estudios RetrospectivosRESUMEN
ABSTRACT Objective Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. Methods This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. Results A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. Conclusions PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.
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Inactivation of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene is considerably more frequent in squamous cell lung cancer (SqCLC) than in other subtypes of lung cancer and may be a promising target for this histology. Here, we present the course of diagnosis and treatment of a patient with advanced SqCLC, harboring not only CDKN2A mutation but also PIK3CA amplification, Tumor Mutational Burden-High (>10 mutations/megabase), and a Tumor Proportion Score of 80%. After disease progression on multiple lines of chemotherapy and immunotherapy, he responded favorably to treatment with the CDK4/6i Abemaciclib and later achieved a durable partial response to immunotherapy rechallenge with a combination of anti-PD-1 and anti-CTLA-4, nivolumab, and ipilimumab.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Fosfatidilinositol 3-Quinasa Clase I/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Células Epiteliales , Inmunoterapia , Ipilimumab/uso terapéutico , Neoplasias Pulmonares/genética , Mutación , Nivolumab/uso terapéuticoRESUMEN
Immune checkpoint inhibitors (ICI) have drastically changed the landscape of metastatic melanoma management, thus significantly improving survival. Clinically, assessing treatment response may be challenging in a portion of cases due to a massive influx of immune cells into the tumor microenvironment, causing a transient increase in the target lesion size. This phenomenon, coined pseudoprogression, can occur in 5-10% of metastatic patients, and it is commonly followed by a tumor regression. Its incidence, however, may be underestimated, given its ephemeral nature and often being documented in visceral metastatic lesions, which are only assessed by imaging scans every 2-3 months. More recently, ICI has been studied in the neoadjuvant setting, yielding durable pathological responses in patients with cutaneous melanoma. Here, we report a case of a large retroauricular melanoma mass with regional lymph node involvement treated with ipilimumab and nivolumab combination therapy that developed pseudoprogression. Initially documented as an increase in size along with inflammatory features, followed by a dramatic clinical improvement. A complete regression was pathologically documented after 3 months and the patient remains disease-free for 14 months after treatment initiation. In conclusion, we document a pseudoprogression case during neoadjuvant ICI treatment and raise the question of whether the incidence of this phenomenon is higher when observed in superficial lesions, which can be assessed by routine physical exam.
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BACKGROUND: Arginine is considered a semi-essential amino acid in healthy adults and the elderly. This amino acid seems to improve the immune system, stimulate cell growth and differentiation, and increase endothelial permeability, among other effects. For those reasons, it has been theorized that arginine supplementation may be used as an adjuvant to conventional cancer therapy treatments. OBJECTIVE: This review aims to evaluate the existing knowledge of the scientific community on arginine supplementation in order to improve the efficacy of current cancer treatment. RESULTS: Despite the continued efforts of science to improve treatment strategies, cancer remains one of the greatest causes of death on the planet in adults and elderly people. Chemo and radiotherapy are still the most effective treatments but at the cost of significant side effects. CONCLUSION: Thus, new therapeutic perspectives have been studied in recent years, to be used in addition to traditional treatments or not, seeking to treat or even cure the various types of cancer with fewer side effects.