Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer.

Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.

Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain.

OBJECTIVE: Patients' psychological reactions to multigene cancer panel testing might differ compared with the single-gene testing reactions because of the complexity and uncertainty associated with the different possible results. Understanding patients' preferences and psychological impact of multigene panel testing is important to adapt the genetic counselling model. METHODS: One hundred eighty-seven unrelated patients with clinical suspicion of hereditary cancer undergoing a 25-gene panel test completed questionnaires after pretest genetic counselling and at 1 week, 3 months, and 12 months after results to elicit their preferences regarding results disclosure and to measure their cancer worry and testing-specific distress and uncertainty. RESULTS: A pathogenic variant was identified in 38 patients (34 high penetrance and 4 moderate penetrance variants), and 54 patients had at least one variant of uncertain significance. Overall, cancer panel testing was not associated with an increase in cancer worry after results disclosure (P value = .87). Twelve months after results, carriers of a moderate penetrance variant had higher distress and uncertainty scores compared with carriers of high penetrance variants. Cancer worry prior to genetic testing predicted genetic testing specific distress after results, especially at long term (P value <.001). Most of the patients reported the wish to know all genetic results. CONCLUSIONS: Our results suggest that patients can psychologically cope with cancer panel testing, but distress and uncertainty observed in carriers of moderate penetrance cancer variants in this cohort warrant further research.

A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade.

Background: The presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathologic complete response (pCR) and improved outcomes in HER2-positive early-breast cancer (BC) treated with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown. Patients and methods: The PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab [and hormonal therapy if hormone receptor (HR)-positive] for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline (N = 148) and at day 15 (D15) of treatment (N = 134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated. A combined score based on tumor cellularity and TILs (CelTIL) measured at D15 was derived in PAMELA, and validated in D15 samples from 65 patients with HER2-positive disease recruited in the LPT109096 neoadjuvant trial, where anti-HER2 therapy-only was administer for 2 weeks, then standard chemotherapy was added for 24 weeks. Results: In PAMELA, baseline and D15 TILs were significantly associated with pCR in univariate analysis. In multivariable analysis, D15 TILs, but not baseline TILs, were significantly associated with pCR. At D15, TILs and tumor cellularity were found independently associated with pCR. A combined score (CelTIL) taking into account both variables was derived. CelTIL at D15 as a continuous variable was significantly associated with pCR, and patients with CelTIL-low and CelTIL-high scores had a pCR rate of 0% and 33%, respectively. In LPT109096, CelTIL at D15 was found associated with pCR both as a continuous variable and as group categories using a pre-defined cut-off (75.0% versus 33.3%). Conclusions: On-treatment TILs, but not baseline TILs, are independently associated with response following anti-HER2 therapy-only. A combined score of TILs and tumor cellularity measured at D15 provides independent predictive information upon completion of neoadjuvant anti-HER2-based therapy. Clinical trial number: NCT01973660.

Attenuation of the epidemic increase in non-Hodgkin's lymphomas in Spain.

BACKGROUND: Attenuation of the epidemic increase in non-Hodgkin's lymphoma (NHL) incidence has recently been reported in the USA and Nordic European countries. After two decades of steadily increasing NHL, this study sought to ascertain whether a similar stabilisation might have taken place in Spain in recent years. PATIENTS AND METHODS: NHL cases were drawn from 13 population-based Spanish cancer registries with a record of at least 10 years of uninterrupted registration during the period 1975-2004. Overall and age-specific changes in incidence rates were evaluated using change-point Poisson models, which allow for accurate detection and estimation of trend changes. RESULTS: A total of 21 335 NHL cases (11 531 male and 9804 female) were identified. Although overall age- and registry-adjusted incidence rates rose by 5.74% annually among men and 6.58% among women across the period 1975-95, a statistically significant change-point was nevertheless detected in both sexes in 1996, followed by stabilisation. CONCLUSIONS: In Spain, NHL incidence levelled off in 1996 after a sharp increase during the 1970s and 1980s. This stabilisation is, partially at least, linked to the decrease in incidence of AIDS-related lymphomas among young adults.

[Implantation of a hospital registry of hereditary nonpolyposis colorectal cancer]. / Implantación de un registro hospitalario de cáncer colorrectal hereditario sin poliposis.

INTRODUCTION: Identification of patients with hereditary nonpolyposis colorectal cancer (HNPCC) can allow colorectal cancer (CRC) prevention through colonoscopy and polypectomies. The purpose of this study was to report the clinical characteristics of HNPCC families in our registry. PATIENTS AND METHOD: HNPCC was identified using the Amsterdam criteria. Familial clustering of CRC and extracolonic cancers were investigated in families. Individuals at risk were offered annual colonoscopy, starting from the age of 25 years. RESULTS: Twelve HNPCC families were identified. There were 46 cases of CRC in 38 patients. The mean age at diagnosis of CRC was 45.4 +/- 12.7 years (range 25-73 years). In patients with documented disease, right-sided tumors predominated. Eleven patients with extracolonic cancer were identified (six tumors located in the endometrium). Of 43 at-risk individuals, 29 accepted surveillance. CONCLUSIONS: Our data confirm the importance of the family history in identifying HNPCC. This study confirms previously described characteristics in HNPCC, namely, early age at onset of CRC, right-sided predominance, multiple synchronous and metachronous neoplasms, and increased extracolonic cancers. This is the first study of clinical data in a Spanish HNPCC registry.

Implantación de un registro hospitalario de cáncer colorrectal hereditario sin poliposis / Implantation of a hospital registry of hereditary nonpolyposis colorectal cancer

Introducción: La identificación de los pacientes afectados de cáncer colorrectal hereditario sin poliposis (CCRHSP) hace posible la prevención del cáncer colorrectal (CCR), mediante el cribado endoscópico y las polipectomías endoscópicas. La finalidad de nuestro estudio es presentar los datos clínicos de las familias incluidas en nuestro registro de CCRHSP. Pacientes y método: El CCRHSP se identifica mediante los criterios de Ámsterdam. Se analiza la historia familiar de CCR y de neoplasias extracolónicas. Entre las familias identificadas, a los familiares en situación de riesgo se les ofrece la realización de cribado mediante colonoscopia anual, a partir de los 25 años de edad. Resultados: Se identifica a 12 familias que cumplen los criterios de Ámsterdam. En total se presentan 46 casos de CCR en 38 pacientes. La edad media en el momento del diagnóstico es de 45,4 ± 12,7 años, con un rango de entre 25 y 73 años. Entre los pacientes con histología documentada, predominan las lesiones del colon derecho. Se identifica a 11 pacientes con neoplasias extracolónicas (6 localizadas en el endometrio). En total, 29 de 43 familiares de riesgo aceptaron el cribado endoscópico. Conclusiones: Los datos confirman la importancia de la historia familiar para la identificación del CCRHSP. Este estudio confirma las características previamente descritas para el CCRHSP, como la edad temprana de presentación del CCR, la localización preferente en el colon derecho, la presencia de múltiples lesiones sincrónicas o metacrónicas y el incremento de las neoplasias extracolónicas. Éste es el primer estudio con datos clínicos de un registro de CCRHSP en España

Introduction: Identification of patients with hereditary nonpolyposis colorectal cancer (HNPCC) can allow colorectal cancer (CRC) prevention through colonoscopy and polypectomies. The purpose of this study was to report the clinical characteristics of HNPCC families in our registry. Patients and method: HNPCC was identified using the Amsterdam criteria. Familial clustering of CRC and extracolonic cancers were investigated in families. Individuals at risk were offered annual colonoscopy, starting from the age of 25 years. Results: Twelve HNPCC families were identified. There were 46 cases of CRC in 38 patients. The mean age at diagnosis of CRC was 45.4 ± 12.7 years (range 25-73 years). In patients with documented disease, right-sided tumors predominated. Eleven patients with extracolonic cancer were identified (six tumors located in the endometrium). Of 43 at-risk individuals, 29 accepted surveillance. Conclusions: Our data confirm the importance of the family history in identifying HNPCC. This study confirms previously described characteristics in HNPCC, namely, early age at onset of CRC, right-sided predominance, multiple synchronous and metachronous neoplasms, and increased extracolonic cancers. This is the first study of clinical data in a Spanish HNPCC registry

[Employees attitudes to workplace health promotion programs for cancer prevention]. / Actitudes de los trabajadores frente a los programas de promoción de la salud para la prevención del cáncer en el lugar del trabajo.

OBJECTIVE: [corrected] We describe a method for feasibility assessment of workplace health promotion (WHP) programs as a necessary prerequisite of any WHP program. METHODS: A total of 167 employees from five workplace communities participated in the study. A questionnaire on the basic components of feasibility (risk factors, attitudes to workplace health promotion interventions, and social-occupational context) was administered. RESULTS: Risk behaviours were common among the employees interviewed. Health promotion in the workplace was favorably viewed by 79% of subjects but reported participation would be lower. Interventions on diet and physical activity received the highest acceptance. Participation would be greatest among local administration employees. CONCLUSIONS: The method demonstrated its utility in obtaining useful data for designing workplace health promotion interventions.

Actitudes de los trabajadores frente a los programas de promoción de la salud para la prevención del cáncer en el lugar del trabajo / Employees attitudes to workplace health promotion programs for cancer prevention

Objetivo: Presentamos un método para evaluar la factibilidad de los programas de promoción de la salud en el trabajo como paso previo a su diseño. Métodos: Un total de 167 trabajadores de cinco ramas de actividad económica participaron en el estudio. Se administró un cuestionario con preguntas sobre los componentes básicos de la factibilidad (factores de riesgo de cáncer, actitudes hacia los programas de promoción de la salud y entorno sociolaboral). Resultados: Las conductas de riesgo para el cáncer son frecuentes entre los trabajadores entrevistados. Un 79 por ciento demostró interés por los programas de promoción de la salud, pero la participación sería inferior. Dieta y ejercicio físico serían los factores de riesgo más susceptibles a la intervención. La participación más alta se hallaría entre los trabajadores de la administración local. Conclusiones: La información obtenida parece válida y útil para orientar el objeto y la planificación de un programa promoción de la salud en el trabajo (AU)

Objetive: We describe a method for feasibility assessment of workplace health promotion (WHP) programs as a necessary prerequisite of any WHP program. Methods: A total of 167 employees from five workplace communities participated in the study. A questionnaire on the basic components of feasibility (risk factors, attitudes to workplace health promotion interventions, and social-occupational context) was administered. Results: Risk behaviours were common among the employees interviewed. Health promotion in the workplace was favorably viewed by 79% of subjects but reported participation would be lower. Interventions on diet and physical activity received the highest acceptance. Participation would be greatest among local administration employees. Conclusions: The method demonstrated its utility in obtaining useful data for designing workplace health promotion interventions (AU)

Influence of stage at diagnosis on survival differences for rectal cancer in three European populations.

Important differences have recently been highlighted between European countries in the survival of colorectal cancer patients. As data on stage at diagnosis were available for rectal cancers in three European population-based registries (Geneva Switzerland; Côte d'Or, France; Mallorca, Spain), we compared relative survival while assessing the effect of stage in a multiple regression model. We analysed 1005 rectal cancer cases diagnosed between 1982 and 1987 and followed up for at least 5 years. In the Mallorca registry, 16% of the patients were diagnosed in the TNM stage I (versus 21% in the Côte d'Or registry and 29% in the Geneva registry, P < 10(-4)) and the 5-year relative survival rate was lower (35%) than in the other two registries (Côte d'Or 47%, Geneva 48%, P = 0.01). In the multivariate analysis, stage was the only independent prognostic factor, whereas the excess death risk did not vary significantly among registries (compared to Geneva, Côte d'Or relative risk was 1.0, Mallorca relative risk 1.11, 95% confidence interval 0.76-1.32 and 0.85-1.44 respectively). Survival differences between the registries were mainly due to stage at diagnosis. Thus, diagnostic conditions appear to be the main determinant of the survival inequalities found in those three European populations.

Comparability of colorectal cancer survival data in three European population-based registries.

During the first part of a study that aimed to compare the survival of persons with colorectal cancers, the comparability of data collected by the Geneva Cancer Registry, the Côte d'Or Cancer Registry and the Mallorca Cancer Registry was investigated, as well as the feasibility of obtaining a common reliable stage classification at diagnosis. The validity of incidence and follow-up data was high in the three registries but completeness appeared to be slightly lower in the Mallorca Cancer Registry than in the other two registries. Comparison of incidence curves, by age, showed that a discrepancy appeared over 75 years, which could correspond to an under-diagnosis or an under-registration of some cases among the elderly in the Côte d'Or and the Mallorca Cancer Registries. Stage classification was stratified by surgical treatment in order to improve the homogeneity of investigations undergone by the patients in each class. Stage distribution and stage-specific survival were consistent with those observed in other population-based series. This study shows that it would be better to restrict comparisons of the survival of persons with colorectal cancer to patients under 75 years, and that stage specific survival comparisons are possible with data routinely collected by registries.

Blood transfusion has no effect on colorectal cancer survival. A population-based study.

This study was conducted to evaluate the impact on survival of perioperative blood transfusion in a series of 698 colorectal cancer patients undergoing radical surgery. Patients were identified, and follow-up was carried out by the local population-based cancer registry. Data on blood transfusion was obtained by record linkage with the files of the blood banks operating in the area covered by the registry. Prognostic factors were age, Dukes stage and topography of the primary tumour. Relative risk (RR) for Dukes B patients was 1.53 [95% confidence interval (CI) 0.94-2.50] and for Dukes C, 3.57 (95% CI 2.22-5.75) when compared with Dukes A patients. For the left colon, RR was 0.96 (0.61-1.52) and for the rectum 1.87 (1.22-2.86) when compared with the right colon. When adjusting for these factors and excluding operative mortality, RR for transfused patients was 1.16 (95% CI 0.87-1.55). It is concluded that blood transfusion does not adversely affect survival in colorectal cancer patients.