Estudio de concordancia entre el 8-gene Score y otros test moleculares comerciales (MammaPrint®, Oncotype DX®) para decidir la necesidad de quimioterapia adyuvante en pacientes con cáncer de mama positivo para receptores hormonales

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 22-06-2017El CM infiltrante es el tumor maligno más frecuente en la mujer en los países occidentales y constituye un grupo heterogéneo de neoplasias. La QT adyuvante se administra en muchos casos tras la cirugía con el fin de reducir el riesgo de recaída. La decisión sobre qué pacientes deben recibir estos tratamientos se establece según criterios clínico-patológicos clásicos que son poco precisos, de manera que para complementar la información suministrada por estos criterios se han introducido herramientas predictivas basadas en perfiles de expresión génica. Tales instrumentos permiten un uso de la QT adyuvante restringido a las pacientes con mayor riesgo. En nuestro entorno, los perfiles génicos de mayor recorrido son Oncotype DX® y MammaPrint®. En el presente estudio se examinó la concordancia entre estos perfiles clásicos y el 8-gene Score, un nuevo perfil génico desarrollado por el equipo investigación de Biología Molecular del HULP. El principal hallazgo del trabajo fue que existe poca correlación entre perfiles génicos, especialmente a la hora de identificar a las pacientes de alto riesgo, lo que supondría prescindir de la QT en este grupo de peor pronóstico. Por lo tanto, y en ausencia de estudios de validación adecuados, no se puede recomendar la utilización de 8-gene Score en la práctica clínica diaria. Los resultados se sitúan en la línea de otros trabajos que han comparado plataformas génicas y que también han encontrado escasa concordancia. Por otro lado, se analizó la influencia que tenía el resultado de los perfiles génicos en cuanto a la administración de QT. El porcentaje de cambio fue del 32%, con una reducción del uso de la QT de un 14%. Finalmente, se comprobó que las técnicas de IHQ para determinar los receptores hormonales y HER2 tienen la misma fiabilidad que la determinación por expresión génica

Increased quality of life in patients with breakthrough cancer pain after individualized therapy : the CAVIDIOM study

Aim: To evaluate the quality of life (QoL) in patients with breakthrough cancer pain (BTcP) in Spanish medical oncology departments. Patients & methods: In a prospective, observational, multicenter study, we assessed QoL using the EQ-5D-5L instrument at baseline and after 15 and 30 days of individualized BTcP therapy, as well as BTcP characteristics and treatment. Results: Patients (n = 118) were mainly women, over 64 years old and with advanced cancer. QoL improved at 15 (p = 0.013) and 30 days (p = 0.011) versus baseline. Individualized BTcP therapy consisted mostly of rapid-onset opioids (transmucosal fentanyl at doses of 67-800 μg) according to the physician evaluation. BTcP improved, including statistically significant reductions in intensity, duration, number of episodes in the last 24 h and time to onset of BTcP relief. Conclusion: QoL increased after individualized pain therapy in patients with advanced cancer and BTcP in medical oncology departments. Keywords: breakthrough cancer pain; medical oncology; quality of life; rapid-onset opioids; transmucosal fentanyl

Evaluation of ERBB2 mRNA Expression in HER2-Equivocal (2+) Immunohistochemistry Cases

Xpert Breast Cancer STRAT4 is a RT-qPCR platform that studies the mRNA expression of ESR1, PGR, MKI67 and ERBB2, providing a positive or negative result for each of these breast cancer biomarkers. Its concordance with immunohistochemistry (IHC) and in situ hybridization (ISH) has been previously demonstrated, but none of the previous works was focused on HER2-equivocal (2+) cases identified by IHC. Thus, we studied the concordance between IHC/ISH and STRAT4 results for 112 HER2 2+ IBC samples, using 148 HER2 0+, 1+ and 3+ (no-HER2 2+) samples for comparison. We found 91.3% accuracy for the determination of HER2 status globally, 99.3% for no-HER2 2+ samples and 80.7% for HER2 2+ samples. Regarding the other biomarkers, we obtained 96.4% accuracy for estrogen receptor, 84.1% for progesterone receptor and 58.2% for Ki67. Our results suggest that the use of ERBB2 mRNA for the evaluation of HER2 2+ cases is not a reliable reflex method to assess the ERBB2 amplification status.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project “PI22/01892” and co-funded by the European Union. Developed with the financial support of Immune4ALL Project (PMP22/00054), with European funds of the Recovery, Transformation and Resilence Plan, and financed by the Instituto de Salud Carlos IIII. Funden by CIBERONC (grants CB16/12/00316 and CB16/12/00295) and the European Development Regional Fund “A way to achieve Europe” (FEDER). Cepheid provided material support for this study

Discordant Humoral and T-Cell Response to mRNA SARS-CoV-2 Vaccine and the Risk of Breakthrough Infections in Women with Breast Cancer, Receiving Cyclin-Dependent Kinase 4 and 6 Inhibitors

Few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). We conducted a prospective, single-center study of patients with breast cancer treated with CDK4/6i who received mRNA-1273 vaccination, as well as a comparative group of healthcare workers. The primary endpoint was to compare the rate and magnitude of humoral and T-cell response after full vaccination. A better neutralizing antibody and anti-S IgG level was observed after vaccination in the subgroup of women receiving CDK4/6i, but a trend toward a reduced CD4 and CD8 T-cell response in the CDK4/6i group was not statistically significant. There were no differences in the rate of COVID-19 after vaccination (19% vs. 12%), but breakthrough infections were observed in those with lower levels of anti-S IgG and neutralizing antibodies after the first dose. A lower rate of CD4 T-cell response was also found in those individuals with breakthrough infections, although a non-significant and similar level of CD8 T-cell response was also observed, regardless of breakthrough infections. The rate of adverse events was higher in patients treated with CDK4/6i, without serious adverse events. In conclusion, there was a robust humoral response, but a blunted T-cell response to mRNA vaccine in women receiving CDK4/6i, suggesting a reduced trend of the adaptative immune response

Broad consensus on the optimal sequence for the systemic treatment of metastatic breast cancer: results from a survey of spanish medical oncologists

Objective: The aim of this survey conducted by 20 leading Spanish oncologists was to analyze the concurrence between Spanish clinical practice and the recently published definition of the optimal sequence for the systemic treatment of metastatic breast cancer (MBC) according to patient profiles. Methods: A self-administered questionnaire was developed, divided into five sections comprising 34 specific questions related to sequential treatments, plus three additional general questions. Respondents were asked to justify negative answers. Participants were recruited randomly by invitation out of a total of 619 oncologists. The questionnaire was sent and collected via e-mail between October 2015 and May 2016. A total of 191 completed questionnaires were received. Results: Overall, 70% of oncologists would keep the three patient profiles exactly as proposed (hormone receptor-positive and HER2-negative, HER2-positive, and triple negative breast cancer). Affirmative answers to questions regarding treatment sequences for these patient profiles (1-34) ranged from 77.8-99.5%, with an average of 90.9% of oncologists being in agreement with the recommended sequential treatments. The lowest degree of consensus was observed for endocrine treatments in pre-menopausal women and for chemotherapy options in hormone-resistant patients, whilst the highest degree of consensus was reached for targeted therapies in HER2-positive patients and for endocrine therapy in post-menopausal women. In their comments, participants revealed a number of economic constraints that prevented them from implementing some of the best treatment options. Conclusions: In conclusion, despite the complexity of MBC treatment, there is general agreement on the optimal treatment sequences