Selection of neoadjuvant treatment based on the 21-GENE test results in luminal breast cancer.

Neoadjuvant chemotherapy (NAC) is an optimal option in early breast cancer, but in ER-positive/HER2-negative (luminal) is still controversial, although a survival benefit has recently been observed when a histological response by Symmans' method type 0 or I is achieved. The 21-gene Oncotype DX Breast Recurrence Score® assay (Oncotype DX®) is a validated test to assess the survival benefit of adjuvant chemotherapy in these patients but its role in the neoadjuvant setting is less established. We analyzed the results of the Oncotype DX® test in a cohort of 122 consecutive patients selected to receive NAC based on classical clinicopathological parameters and the correlation between the Oncotype DX® results and the pathological response assessed by Symmans' method. Median age was 56.5 (range 31-84) years. Initial tumor size was T1 (<20 mm) in 46 patients (37.7%), 57 (46.7%) had a T2 tumor (20-50 mm), and 19 (15.6%) had a tumor size more than 50 mm. 59 (48.4%) had axillary node involvement. The median expression estrogen and progesteron receptors by immunohistochemistry was 280 and 120 respectively and median Ki67 index was 28%. The Recurrence Score (RS) results were <11 in 21 patients (17.2%) patients, RS 11 to 25 in 58 (47.5%), and RS > 25 in 43 (35.2%). Considering the Oncotype DX test results, neoadjuvant chemotherapy was administered to 60 patients (49%), 11 (9%) received adjuvant chemotherapy and 51 (42%) no chemotherapy. Testing with the assay has therefore led to 42% fewer chemotherapy treatments. Among 60 patients receiving NAC, pathologic response was achieved for 5 patients (8.3%) with RCB-0 and 15 RCB-1 (25%). We did not find any pathological response RCB-0 and RCB-I in the 20 patients who received NAC and had a Recurrence Score result <21 for the premenopausal group, or a RS result <25 for the postmenopausal group. For patients with highest Recurrence Score results (RS > 21 or 25 according to menopausal status) it was 12% (5/40) RCB-0 and 40% (16/40) RCB-I. CONCLUSIONS: The Oncotype DX test could be a useful tool to select patients candidates for neoadjuvant chemotherapy in luminal breast cancer. Neoadjuvant chemotherapy could be avoided in 42% of patients. We found a correlation between Recurrence Score results and pathological response with 14% of RCB-0 and a total of 47% of significant pathological response type RCB-0 and RCB-I in patients with highest Recurrence Score results. Interestingly, patients with a Recurrence Score result inferior to 32 did not get any histological response type 0 and only 5% RCB-I.

Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: a pilot clinical trial.

BACKGROUND: Preclinical research suggests that the efficacy of immune checkpoint inhibitors in breast cancer can be enhanced by combining them with antiangiogenics, particularly in a sequential fashion. We sought to explore the efficacy and biomarkers of combining the anti-PD-L1 durvalumab plus the antiangiogenic bevacizumab after bevacizumab monotherapy for advanced HER2-negative breast cancer. METHODS: Patients had advanced HER2-negative disease that progressed while receiving single-agent bevacizumab maintenance as a part of a previous chemotherapy plus bevacizumab regimen. Treatment consisted of bi-weekly durvalumab plus bevacizumab (10 mg/kg each i.v.). Peripheral-blood mononuclear cells (PBMCs) were obtained before the first durvalumab dose and every 4 weeks and immunophenotyped by flow-cytometry. A fresh pre-durvalumab tumor biopsy was obtained; gene-expression studies and immunohistochemical staining to assess vascular normalization and characterize the immune infiltrate were conducted. Patients were classified as "non-progressors" if they had clinical benefit (SD/PR/CR) at 4 months. The co-primary endpoints were the changes in the percentage T cell subpopulations in PBMCs in progressors versus non-progressors, and PFS/OS time. RESULTS: Twenty-six patients were accrued. Median PFS and OS were 3.5 and 11 months; a trend for a longer OS was detected for the hormone-positive subset (19.8 versus 7.4 months in triple-negatives; P = 0.11). Clinical benefit rate at 2 and 4 months was 60% and 44%, respectively, without significant differences between hormone-positive and triple-negative (P = 0.73). Non-progressors' tumors displayed vascular normalization features as a result of previous bevacizumab, compared with generally abnormal patterns observed in progressors. Non-progressors also showed increased T-effector and T-memory signatures and decreased TREG signatures in gene expression studies in baseline-post-bevacizumab-tumors compared with progressors. Notably, analysis of PBMC populations before durvalumab treatment was concordant with the findings in tumor samples and showed a decreased percentage of circulating TREGs in non-progressors. CONCLUSIONS: This study reporting on sequential bevacizumab+durvalumab in breast cancer showed encouraging activity in a heavily pre-treated cohort. The correlative studies agree with the preclinical rationale supporting an immunopriming effect exerted by antiangiogenic treatment, probably by reducing TREGs cells both systemically and in tumor tissue. The magnitude of this benefit should be addressed in a randomized setting. TRIAL REGISTRATION: (www.clinicaltrials.gov): NCT02802098 . Registered on June 16, 2020.

Randomized Phase 0/I Trial of the Mitochondrial Inhibitor ME-344 or Placebo Added to Bevacizumab in Early HER2-Negative Breast Cancer.

PURPOSE: We previously demonstrated that mitochondrial inhibitors' efficacy was restricted to a metabolic context in which mitochondrial respiration was the predominant energy source, a situation achievable by inducing vascular normalization/hypoxia correction with antiangiogenics. Vascular normalization can be tracked with 2[18F]fluoro-2-deoxy-d-glucose (FDG)-PET. We tested the efficacy of the mitochondrial inhibitor ME-344 or placebo added to bevacizumab in early breast cancer. PATIENTS AND METHODS: Treatment-naïve HER2-negative patients with T > 1 cm (any N) underwent a breast-centered 18F-fluorodeoxyglucose (FDG)-PET (day 1) and received a single dose of bevacizumab (15 mg/kg), followed by a second FDG-PET (day 8). Patients were then randomized (1:1) to Arm A (ME-344 10 mg/kg intravenous on days 8, 15, and 21) or Arm B (placebo). Tumors were biopsied on days 0 and 29. Succinate dehydrogenase enzyme histochemistry (SDH-EHC), confocal microscopy of vessel architecture, and HIF1α staining were performed in pre- and posttreatment biopsies to assess the pharmacodynamics, vessel normalization, and tissue re-oxygenation by bevacizumab, respectively. RESULTS: ME-344 displayed significant biological activity versus placebo: compared with a 186% increase in Arm B, Ki67 decreased by 23.4% from days 0 to 28 in Arm A (P < 0.001) (N = 42 patients). FDG-PET predicted vascular normalization in about one-third of the patients in each arm, which was confirmed using confocal microscopy and HIF1α staining. In the subgroup with vascular normalization, ME-344 induced a Ki67 decrease of 33.4% (placebo: 11.8 increase). SDH-EHC suggested on-target effects of ME-344. CONCLUSIONS: ME-344 has significant biological antitumor activity in HER2-negative breast cancer, particularly after induction of vascular normalization and tissue reoxygenation with bevacizumab.

Prevalencia de la adherencia terapéutica a opioides mayores en una muestra de pacientes oncológicos avanzados. Estudio piloto / Prevalence of the therapeutic adherence to strong opioids analgesics in a sample of advanced cancer patients. A pilot study

OBJETIVO: Determinar la prevalencia de adherencia terapéutica a opioides mayores de la escala analgésica de la Organización Mundial de la Salud (OMS) medida con el test 4-ítem Morisky Medication Adherence Scale (MMAS-4), en una muestra de pacientes oncológicos avanzados. Conocer los factores asociados a adherencia terapéutica en este tipo de paciente. MATERIAL Y MÉTODO: Estudio observacional prospectivo realizado en la Región Sanitaria de Lleida entre septiembre de 2013 y marzo de 2014. Se incluyeron 89 pacientes oncológicos avanzados consecutivamente, atendidos por equipos específicos de fin de vida, ya sea en el domicilio (PADES) o bien en la consulta externa de ámbito hospitalario (UFISS). Se utilizó el test autoadministrado MMAS-4. RESULTADOS: Se incluyeron un total de 89 pacientes de los cuales 48 (54 %) fueron atendidos por PADES y 41 (46 %) por UFISS. Media de edad (70,3 ± 14,1 años). Pacientes varones 64 (72 %). La dosis equivalente de morfina diaria (MEDD) fue de 76,26 ± 74,73 mg. Un total de 47 pacientes (52,8 %) presentaron adherencia al tratamiento. Haber recibido analgésicos por vía transdérmica es un factor que contribuye a la mala adherencia terapéutica (p = 0,006) y fallar la pregunta D del MMAS-4 junto con género femenino contribuye a la mala adherencia terapéutica (p = 0,027). DISCUSIÓN: Se detecta un 52,8 % de adherencia terapéutica a opioides del tercer escalón de la OMS en la muestra estudiada

AIM: To determine the prevalence of the therapeutic adherence to strong opioids analgesics (third step of the analgesic ladder of the World Health Organization [WHO]) in a sample of advanced cancer patients using the Morisky-Green-Levine tool (MMAS-4) and to know the factors associated. METHODS: Observational and prospective study carried out in the Sanitary Region of Lleida between September 2013 and March 2014. A total of 89 advanced cancer patients consecutively attended by end-of-life specific teams both at home (PADES) and at the hospital (UFISS) were included. The self-administered 4-items Morisky-Green-Levine test was used. RESULTS: Mean of age (70, 3 ± 14, 1 years). Man 64 (72 %). Patients attended by the Home care Team 48 patients (54 %). The Morphine Equivalent Daily Dose (MEDD) was 76.26 ± 74.73 mg. The therapeutic adherence was detected in 47 patients (52.8 %). Factors related to the route of administration of the analgesic (transdermal, p = 0,006) and between female genre and to fail to question D of the MMAS-4 (p = 0,027) were detected in the multivariate analysis. DISCUSSION: We detected a prevalence of therapeutic adherence to the analgesics of the third ladder of the WHO of 52,8 % in the sample studied

Erupción cutánea en una paciente con neoplasia y neutropenia febril / A skin rash in a febrile neutropenic cancer patient

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Virus del papiloma humano en cáncer de pulmón no microcítico. Impacto de mutaciones del EGFR o respuesta a erlotinib / Human Papillomavirus in Non-Small-Cell Lung Cancer: The Impact of EGFR Mutations and the Response to Erlotinib

Se ha sugerido que el virus del papiloma humano (HPV) puede originar cáncer de pulmón no microcítico (NSCLC). La tasa de infección HPV es mayor en NSCLC de asiáticos, no fumadores, con adenocarcinoma o respuesta a inhibidores tirosín-cinasa del receptor del factor de crecimiento epidérmico (EGFR-TKI). Hemos explorado retrospectivamente la relación entre mutaciones EGFR o respuesta a EGFR-TKI e infección HPV en 40pacientes con NSCLC, considerando el impacto del sexo, de la edad, del subtipo histológico, del tabaquismo y del tipo de muestra. La tasa de infección HPV fue del 2,5%, y no influía ninguna variable analizada, aunque el escaso tamaño muestral no permite conclusiones definitivas. La tasa de infección HPV en NSCLC debería revisarse en pacientes con mutaciones EGFR o tendencia a presentarlas(AU)

It has been suggested that human papillomavirus (HPV) could participate in the development of non-small-cell lung cancer (NSCLC). A higher HPV infection rate has been reported in the NSCLC samples from Asian non-smoker patients, with adenocarcinomas or responders to EGFR tyrosine kinase inhibitors (EGFR-TKI). We explored a potential relationship between EGFR mutation, response to EGFR-TKI and HPV infection in Western NSCLC patients. We retrospectively analyzed 40 NSCLC samples and the impact of age, gender, histology, tobacco habit and sample type. HPV infection rate was 2.5% and it was not statistically modified by any analyzed variable, although the limited sample size did not provide definitive conclusions. The rate of HPV infection in NSCLC should be studied in patients with EGFR mutations or a tendency towards presenting them(AU)

Human papillomavirus in non-small-cell lung cancer: the impact of EGFR mutations and the response to erlotinib.

It has been suggested that human papillomavirus (HPV) could participate in the development of non-small-cell lung cancer (NSCLC). A higher HPV infection rate has been reported in the NSCLC samples from Asian non-smoker patients, with adenocarcinomas or responders to EGFR tyrosine kinase inhibitors (EGFR-TKI). We explored a potential relationship between EGFR mutation, response to EGFR-TKI and HPV infection in Western NSCLC patients. We retrospectively analyzed 40 NSCLC samples and the impact of age, gender, histology, tobacco habit and sample type. HPV infection rate was 2.5% and it was not statistically modified by any analyzed variable, although the limited sample size did not provide definitive conclusions. The rate of HPV infection in NSCLC should be studied in patients with EGFR mutations or a tendency towards presenting them.