Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study.

BACKGROUND: Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. METHODS: This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. RESULTS: From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. CONCLUSIONS: Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT01733628.

Clinical and Sociodemographic Determinants of Adherence to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Recommendations in Breast Cancer Survivors-Health-EpiGEICAM Study.

Breast cancer (BC) survivors are advised to follow the WCRF/AICR cancer prevention recommendations, given their high risk of developing a second tumour. We aimed to explore compliance with these recommendations in BC survivors and to identify potentially associated clinical and sociodemographic factors. A total of 420 BC survivors, aged 31-80, was recruited from 16 Spanish hospitals. Epidemiological, dietary and physical activity information was collected through questionnaires. A 7-item score to measure compliance with the recommendations was built according to the 2018 WCRF/AICR scoring criteria. Standardized prevalences and standardized prevalence ratios of moderate and high compliance across participant characteristics were estimated using multinomial and binary logistic regression models. The mean score was 3.9 (SD: 1.0) out of 7 points. Recommendations with the worst adherence were those of limiting consumption of red/processed meats (12% of compliance, 95% CI: 8.2-15.0) and high fibre intake (22% of compliance, 95% CI: 17.6-27.0), while the best compliance was observed for the consumption of fruits and vegetables (73% of compliance, 95% CI: 69.2-77.7). Overall, adherence was worse in women with university education and in those with first-degree relatives with BC. This information may be of interest to design and implement personalized preventive measures adapted to the characteristics of these patients.

Patient-reported experience in lung and breast cancer through a patient journey.

OBJECTIVE: To analyse a patient journey based on the experience reported by  breast and lung cancer patients at Spanish hospital. Method: A mixed design was used, with interviews with 16 health  professionals and 25 patients (qualitative method) and a Net Promoter Score questionnaire to 127 patients (quantitative method). INCLUSION CRITERIA: oncology patients > 18 years treated in hospital between February-  May 2019. EXCLUSION CRITERIA: paediatric patients, in palliative care or who were  hospitalised at the time of the study. RESULTS: Six phases were identified from the data obtained in the qualitative method: my life before diagnosis; discovery; initiation; treatment;  followup; and my current life. In the my life before diagnosis phase, a  functional level of experience was established, as patients' lives met their  expectations. In the discovery phase, patients' expectations were observed to  be met, although several satellite experiences were found. In the initiation  phase, the experience tended to be negative due to long waiting times and  emotional and physical stress. The treatment phase was defined as a basic- poor experience, due to waiting times and lack of institutional support. The  experience in the follow-up phase was positive in terms of tests and visits, but  critical points were observed in waiting times. In the current phase, the effort  made by health professionals to ensure the best possible treatment and care  was mentioned. In terms of quantitative analysis, a positive score (46%) was obtained for the Net Promoter Score indicator, as 60% of patients were promoters, i.e. they were satisfied with the service offered by the hospital. CONCLUSIONS: This study provides insight into the experience of cancer patients in the six main stages of the disease. The most positive phases were "my life before diagnosis" and "follow-up" while the phases with a negative trend were "initiation" and "treatment" due to the waiting times  and the emotional burden on the patient.

OBJETIVO: Analizar la experiencia aportada por los pacientes con cáncer de  mama y pulmón utilizando la metodología del recorrido del paciente en un  hospital español. Método: Se empleó un diseño mixto, con entrevistas a 16 profesionales sanitarios y 25 pacientes (método cualitativo), y un cuestionario  basado en el indicador Net Promoter Score a 127 pacientes (método  cuantitativo). Criterios de inclusión: pacientes oncológicos > 18 años tratados  en el hospital entre febrero y mayo de 2019. Criterios de exclusión: pacientes pediátricos, en cuidados paliativos o que estaban hospitalizados en el  momento del estudio. RESULTADOS: Se identificaron seis fases a partir de los datos obtenidos en  el  método cualitativo: mi vida antes del diagnóstico, descubrir, comenzar, tratamiento, seguimiento y mi vida hoy. En la fase mi vida antes del  diagnóstico se estableció un nivel de experiencia funcional, ya que la vida  cumplía las expectativas de los pacientes. En la fase de descubrir se observó  que las expectativas de los pacientes se cumplían, aunque se  encontraron varias experiencias satélite. En la fase comenzar, la experiencia  tendió a ser negativa debido a los largos tiempos de espera y al estrés  emocional y físico. La fase de tratamiento se consideró como una experiencia  de nivel básico-deficiente, debido a los tiempos de espera y a la falta de apoyo  institucional. La experiencia en la fase de seguimiento fue positiva respecto   las pruebas y las visitas, pero se observaron puntos críticos en los tiempos de espera. en la fase mi vida hoy se mencionó el esfuerzo realizado  por  los profesionales sanitarios para garantizar el mejor tratamiento y  atención posibles. En cuanto al análisis cuantitativo, se obtuvo una puntuación positiva (46%) para el indicador Net Promoter Score, ya que el 60% de los  pacientes pertenecían a la categoría de promotores, es decir, estaban satisfechos con el servicio ofrecido por el hospital. CONCLUSIONES: Este estudio permite conocer la experiencia de los pacientes  oncológicos en las seis etapas principales de la enfermedad. Las fases más  positivas fueron "mi vida antes del diagnóstico" y "seguimiento", mientras que  las fases con tendencia negativa fueron "inicio" y "tratamiento" debido a los  tiempos de espera y la carga emocional que suponen para el paciente.

La experiencia del paciente en el cáncer de pulmón y de mama a través del recorrido del paciente / Patient-reported experience in lung and breast cancer through a patient journey

Objetivo: Analizar la experiencia aportada por los pacientes concáncer de mama y pulmón utilizando la metodología del recorrido delpaciente en un hospital español.Método: Se empleó un diseño mixto, con entrevistas a 16 profesionalessanitarios y 25 pacientes (método cualitativo), y un cuestionario basadoen el indicador Net Promoter Score a 127 pacientes (método cuantitativo). Criterios de inclusión: pacientes oncológicos > 18 años tratados enel hospital entre febrero y mayo de 2019. Criterios de exclusión: pacientes pediátricos, en cuidados paliativos o que estaban hospitalizados enel momento del estudio.Resultados: Se identificaron seis fases a partir de los datos obtenidos enel método cualitativo: mi vida antes del diagnóstico, descubrir, comenzar,tratamiento, seguimiento y mi vida hoy. En la fase mi vida antes del diagnóstico se estableció un nivel de experiencia funcional, ya que la vida cumplía las expectativas de los pacientes. En la fase de descubrir se observóque las expectativas de los pacientes se cumplían, aunque se encontraronvarias experiencias satélite. En la fase comenzar, la experiencia tendió aser negativa debido a los largos tiempos de espera y al estrés emocionaly físico. La fase de tratamiento se consideró como una experiencia de nivelbásico-deficiente, debido a los tiempos de espera y a la falta de apoyoinstitucional. La experiencia en la fase de seguimiento fue positiva respectoa las pruebas y las visitas, pero se observaron puntos críticos en los tiemposde espera. En la fase mi vida hoy se mencionó el esfuerzo realizado polos profesionales sanitarios para garantizar el mejor tratamiento y atención posibles. En cuanto al análisis cuantitativo, se obtuvo una puntuaciónpositiva (46%) para el indicador Net Promoter Score, ya que el 60% delos pacientes pertenecían a la categoría de promotores, es decir, estabansatisfechos con el servicio ofrecido por el hospital. (AU)

Objective: To analyse a patient journey based on the experience reported by breast and lung cancer patients at Spanish hospital.Method: A mixed design was used, with interviews with 16 health professionals and 25 patients (qualitative method) and a Net Promoter Scorequestionnaire to 127 patients (quantitative method). Inclusion criteria:oncology patients > 18 years treated in hospital between February- May2019. Exclusion criteria: paediatric patients, in palliative care or whowere hospitalised at the time of the study.Results: Six phases were identified from the data obtained in the qualitative method: my life before diagnosis; discovery; initiation; treatment; followup; and my current life. In the my life before diagnosis phase, a functionallevel of experience was established, as patients’ lives met their expectations.In the discovery phase, patients’ expectations were observed to be met,although several satellite experiences were found. In the initiation phase, theexperience tended to be negative due to long waiting times and emotionaland physical stress. The treatment phase was defined as a basic-poor experience, due to waiting times and lack of institutional support. The experiencein the follow-up phase was positive in terms of tests and visits, but criticalpoints were observed in waiting times. In the current phase, the effort madeby health professionals to ensure the best possible treatment and care wasmentioned. In terms of quantitative analysis, a positive score (46%) wasobtained for the Net Promoter Score indicator, as 60% of patients werepromoters, i.e. they were satisfied with the service offered by the hospital. (AU)

Malignancies in Deceased Organ Donors: The Spanish Experience.

BACKGROUND: To better define the risk of malignancy transmission through organ transplantation, we review the Spanish experience on donor malignancies. METHODS: We analyzed the outcomes of recipients of organs obtained from deceased donors diagnosed with a malignancy during 2013-2018. The risk of malignancy transmission was classified as proposed by the Council of Europe. RESULTS: Of 10 076 utilized deceased donors, 349 (3.5%) were diagnosed with a malignancy. Of those, 275 had a past (n = 168) or current (n = 107) history of malignancy known before the transplantation of organs into 651 recipients. Ten malignancies met high-risk criteria. No donor-transmitted cancer (DTC) was reported after a median follow-up of 24 (interquartile range [IQR]: 19-25) mo. The other 74 donors were diagnosed with a malignancy after transplantation. Within this group, 64 donors (22 with malignancies of high or unacceptable risk) whose organs were transplanted into 126 recipients did not result in a DTC after a median follow-up of 26 (IQR: 22-37) mo, though a prophylactic transplantectomy was performed in 5 patients. The remaining 10 donors transmitted an occult malignancy to 16 of 25 recipients, consisting of lung cancer (n = 9), duodenal adenocarcinoma (n = 2), renal cell carcinoma (n = 2), extrahepatic cholangiocarcinoma (n = 1), prostate cancer (n = 1), and undifferentiated cancer (n = 1). After a median follow-up of 14 (IQR: 11-24) mo following diagnosis, the evolution was fatal in 9 recipients. In total, of 802 recipients at risk, 16 (2%) developed a DTC, which corresponds to 6 cases per 10 000 organ transplants. CONCLUSIONS: Current standards may overestimate the risk of malignancy transmission. DTC is an infrequent but difficult to eliminate complication.

Type does matter. Use VIRGIN olive oil as your preferred fat to reduce your risk of breast cancer: case-control EpiGEICAM study.

The Epi-GEICAM study comprises 1017 invasive BC cases matched with controls of similar age (49 ± 9 years) and residence. Diet and OO consumption were collected through a validated food frequency questionnaire. 75% of women referred OO, common (refined) or virgin, as the main fat source. Using conditional logistic regression models, we compared different scenarios of type and frequency of OO consumption, using as reference those women not always using OO for the three culinary practices (seasoning, cooking, and frying) and adding <2 tablespoons (tbsps.) per day during the meal to bread, salad, or dishes. A substantial inverse association was observed in those women always using VOO for the three culinary practices and consuming ≥2 tbsps. of OO per day during meals (adjusted OR, 0.72; 95% CI: 0.51, 1.03; P = 0.07). Potential benefits from OO consumption, at least as regards the protection provided for BC, could be mostly conferred with VOO, and when its consumption is high.

Low-grade triple-negative breast carcinomas. A report of 2 cases and an update of current concepts.

Triple negative breast cancer is defined by the lack of expression of estrogen, progesterone and HER2 receptors. Significant molecular, morphological and clinical heterogeneity is present in this group of neoplasms. Although the majority are high-grade tumors, low-grade triple negative breast cancers can occur and their evolution, molecular characteristics and therapeutic management vary from the former. In the current review, we focus on the histological and immunohistochemical phenotypes of two new low-grade cases: an acinic cell carcinoma and an adenoid cystic carcinoma. Data originated from the pathology department of a third-level hospital over an 18-month period, within a breast cancer screening program. Low-grade triple negative cancers should be suspected in triple negative breast cancers with low proliferative rates as, unlike high-grade tumors, they require a multidisciplinary approach. They can be diagnosed at an early stage by immunohistochemistry using core needle biopsy.

Low-grade triple-negative breast carcinomas. A report of 2 cases and an update of current concepts

Triple negative breast cancer is defined by the lack of expression of estrogen, progesterone and HER2 receptors. Significant molecular, morphological and clinical heterogeneity is present in this group of neoplasms. Although the majority are high-grade tumors, low-grade triple negative breast cancers can occur and their evolution, molecular characteristics and therapeutic management vary from the former. In the current review, we focus on the histological and immunohistochemical phenotypes of two new low-grade cases: an acinic cell carcinoma and an adenoid cystic carcinoma. Data originated from the pathology department of a third-level hospital over an 18-month period, within a breast cancer screening program. Low-grade triple negative cancers should be suspected in triple negative breast cancers with low proliferative rates as, unlike high-grade tumors, they require a multidisciplinary approach. They can be diagnosed at an early stage by immunohistochemistry using core needle biopsy.(AU)

El cáncer de mama triple negativo se define por la falta de expresión de receptores de estrógeno, progesterona y HER2. La heterogeneidad molecular, morfológica y clínica en este grupo de neoplasias es significativa. Aunque la mayoría de ellos son tumores de alto grado, existen cánceres de mama triple negativos de bajo grado cuya historia natural, características moleculares y terapia óptima son bastante diferentes a los primeros. En la revisión actual, nos centramos en los fenotipos histológicos e inmunohistoquímicos de 2 nuevos casos de bajo grado: un carcinoma de células acinares y un carcinoma adenoide quístico de bajo grado. Los datos provienen de los diagnósticos realizados por el servicio de anatomía patológica de un hospital terciario durante un período de 18 meses, dentro de un programa de cribado de cáncer de mama. Los cánceres triple negativos de bajo grado deben sospecharse en los cánceres de mama triple negativos con bajas tasas de proliferación y podrían ser diagnosticados precozmente por inmunohistoquímica en biopsia con aguja gruesa, ya que requieren un abordaje multidisciplinario, diferente a los de alto grado.(AU)

Breast cancer mortality after eight years of an improved screening program using digital breast tomosynthesis.

OBJECTIVES: To assess screening quality metrics and to describe mortality rates eight years after redesign of breast cancer screening and diagnosis pathways, and the introduction of digital breast tomosynthesis. SETTING: Breast Unit of the Toledo Health Area in the region of Castilla-La Mancha (Spain). METHODS: We recorded screening metrics and mortality data following the introduction of digital breast tomosynthesis in 2011 for screening and diagnosis pathways. We then compared the mortality between Toledo Health Area and the rest of Castilla-La Mancha, where digital breast tomosynthesis is not available. RESULTS: All screening quality metrics improved following the introduction of digital breast tomosynthesis. The cancer detection rate significantly increased from 2.3 (95% confidence interval (CI): 1.9-3.6) to 4.5 per 1000 women (95% CI: 3.2-5.2) on average between the periods 2005-2009 and 2015-2018, while the recall rate significantly decreased from 7.0% (95% CI: 6.8%-8.2%) to 2.6% (95% CI: 2.0%-3.6%). Comparing breast cancer mortality rates for 2014-2018 in the Toledo Health Area with the rest of Castilla-La Mancha, which had similar cancer treatment access and management protocols but without digital breast tomosynthesis, the crude mortality rate was 17.79 (95% CI: 15.38 -20.19) vs. 24.76 per 100,000 (95% CI: 26.12-23.39), respectively. The cumulative risk of death was also significantly lower for the Toledo Health Area than for Castilla-La Mancha. CONCLUSION: The introduction of digital breast tomosynthesis improved screening quality indicators. Breast cancer mortality simultaneously decreased with respect to the rest of Castilla-La Mancha. Further research is needed to assess the long-term results, and the role that the redesign may have played in reducing mortality.

Derived Neutrophil-to-Lymphocyte Ratio Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: Derived neutrophil-to-lymphocyte ratio (dNLR) is a biomarker associated with clinical outcome in breast cancer (BC). We analyzed the association of dNLR with pathological complete response (pCR) in triple-negative BC (TNBC) patients receiving neoadjuvant chemotherapy (CT). METHODS: This is a retrospective analysis of two randomized studies involving early stage/locally advanced TNBC patients receiving anthracycline/taxane-based CT+/-carboplatin (GEICAM/2006-03) or nab-paclitaxel/paclitaxel followed by anthracycline regimen (ETNA). dNLR was calculated as the ratio of neutrophils to the difference between total leukocytes and neutrophils in peripheral blood before CT (baseline) and at the end of treatment (EOT). Logistic regression analyses were used to explore dNLR association with pCR. RESULTS: In total, 308 TNBC patients were analyzed, 216 from ETNA and 92 from GEICAM/2006-03. Baseline median dNLR was 1.61 (interquartile range (IQR): 1.25-2.04) and at EOT 1.53 (IQR: 0.96-2.22). Baseline dNLR showed positive correlation with increased tumor size (p-value = 1e-04). High baseline dNLR, as continuous variable or using median cutoff, was associated with lower likelihood of pCR in univariate analysis. High EOT dNLR as continuous variable or using quartiles was also associated with lower pCR rate in uni- and multivariate analyses. CONCLUSIONS: High baseline and EOT dNLR correlates with lower benefit from neoadjuvant CT in TNBC.

Real-world effectiveness of dual HER2 blockade with pertuzumab and trastuzumab for neoadjuvant treatment of HER2-positive early breast cancer (The NEOPETRA Study).

PURPOSE: Neoadjuvant clinical trials with dual HER2 blockade with pertuzumab and trastuzumab plus chemotherapy demonstrated high rates of pathological complete response (pCR) in HER2-positive early breast cancer (BC). We investigated whether the benefit on pCR seen in clinical trials is confirmed in a real-world setting. METHODS: Multicenter, retrospective study in patients with HER2-positive early BC receiving neoadjuvant treatment with pertuzumab and trastuzumab in routine clinical practice (n = 243). The primary endpoint was total pCR (tpCR) (ypT0/is ypN0). RESULTS: A total of 243 evaluable patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes in 74.1% of patients, with single-agent taxane in 11.1% of patients and with platinum-based chemotherapy (CT) in 14.4% of patients. The tpCR rate was 66.4%:71% with anthracyclines and taxanes, 59.3% with single-agent taxane, and 48.6% with platinum-based combinations. The tpCR rate was higher among patients with hormone receptor (HR)-negative tumors (80.9%) vs HR-positive tumors (55.4%) (p < 0.001). A pCR in the breast (ypT0/is) was achieved in 67.6% of patients. Of 143 patients who showed radiological complete response (rCR) (62%), 112 (78.3%) patients also achieved tpCR. Assessment of rCR by magnetic resonance imaging (MRI) showed the highest negative predictive value (NPV) for predicting tpCR (83.5%). Breast-conserving surgery was performed in 58.7% of patients. Grade 3 and grade 4 toxicities were reported in 33 (18.2%) and 12 (6.6%) patients, respectively. No toxicity leading to death was reported. CONCLUSIONS: This real-world analysis shows that neoadjuvant pertuzumab, trastuzumab, and chemotherapy achieve comparable or even higher rates of tpCR than those seen in clinical trials. The pCR benefit is higher in HR-negative tumors. The assessment of rCR by MRI showed the highest ability for predicting pCR. In addition, this neoadjuvant strategy confers an acceptable safety profile.

GEICAM Guidelines for the Management of Patients with Breast Cancer During the COVID-19 Pandemic in Spain.

Breast cancer (BC) is the most common cancer in women in Spain. During the COVID-19 pandemic caused by the SARS-CoV-2 virus, patients with BC still require timely treatment and follow-up; however, hospitals are overwhelmed with infected patients and, if exposed, patients with BC are at higher risk for infection and serious complications if infected. Thus, health care providers need to evaluate each BC treatment and in-hospital visit to minimize pandemic-associated risks while maintaining adequate treatment efficacy. Here we present a set of guidelines regarding available options for BC patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the lack of evidence about COVID-19 infection, these recommendations are mainly based on expert opinion, medical organizations' and societies' recommendations, and some published evidence. We consider this a useful tool to facilitate medical decision making in this health crisis situation we are facing. IMPLICATIONS FOR PRACTICE: This work presents a set of guidelines regarding available options for breast cancer (BC) patient management and treatment by BC subtype in the context of the COVID-19 pandemic. Owing to the suddenness of this health crisis, specialists have to make decisions with little evidence at hand. Thus, these expert guidelines may be a useful tool to facilitate medical decision making in the context of a worldwide pandemic with no resources to spare.

Primary breast cancer and health related quality of life in Spanish women: The EpiGEICAM case-control study.

This study evaluates the impact of breast cancer (BC) in health related quality of life (HRQL) and in psychological distress (PD) during the initial phases of the disease and looks for contributing factors. A multicentric case-control study, EpiGEICAM, was carried out. Incident BC cases and age- and residence- matched controls were included. Clinical, epidemiological, HRQL (SF-36) and PD information (GHQ-28) was collected. We used multivariable logistic regression models to estimate OR of low HRQL and of PD in cases compared to controls, and to identify factors associated with low HRQL and with PD. Among 896 BC cases and 890 control women, cases had poorer scores than both, the reference population and the control group, in all SF-36 scales. BC women with lower education, younger, active workers, never smokers, those with comorbidities, in stage IV and with surgical treatment had lower physical HRQL; factors associated with low mental HRQL were dissatisfaction with social support, being current smoker and having children. Cases had a fivefold increased odds of PD compared to controls. Managing comorbidities and trying to promote social support, especially in younger and less educated women, could improve well-being of BC patients.

Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion.

BACKGROUND: Changes in the clinical subtype (CS) and intrinsic subtype (IS) between breast cancer (BC) metastases and corresponding primary tumours have been reported. However, their relationship with tumour genomic changes remains poorly characterised. Here, we analysed the association between genomic remodelling and subtype conversion in paired primary and metastatic BC samples. METHODS: A total of 57 paired primary and metastatic tumours from GEICAM/2009-03 (ConvertHER, NCT01377363) study participants with centrally assessed CS (n = 57) and IS (n = 46) were analysed. Targeted capture and next-generation sequencing of 202 genes on formalin-fixed paraffin-embedded samples was performed. The cancer cell fraction (CCF) of mutations in primary and metastatic pairs was estimated as a surrogate of tumour clonal architecture. Changes in mutation CCF between matched primary and metastatic tumours were analysed in the presence or absence of subtype conversion. FINDINGS: CS conversion occurred in 24.6% and IS conversion occurred in 36.9% of metastases. Primary tumours and metastases had a median of 11 (range, 3-29) and 9 (range, 1-38) mutations, respectively (P = 0.05). Overall, mutations in metastases showed a higher estimated CCF than in primary tumours (median CCF, 0.51 and 0.47, respectively; P = 0.042), consistent with increased clonal homogeneity. The increase in mutation CCF was significant in CS-converted (P = 0.04) but not in IS-converted (P = 0.48) metastases. Clonal remodelling was highest in metastases from hormone receptor-positive and human epidermal growth factor 2 (HER2)-positive tumours (P = 0.006). CONCLUSIONS: Mutations in BC metastases showed significantly higher estimated CCF than primary tumours. CCF changes were more prominent in metastases with CS conversion. Our findings suggest that changes in BC subtypes are linked to clonal remodelling during BC evolution.

Development and validation of a sexual relations satisfaction scale in patients with breast cancer - "SEXSAT-Q".

PURPOSE: Because the currently available questionnaires to evaluate sexual changes on breast cancer women only address the sexual sphere with a few questions our purpose was to develop a questionnaire that assesses changes in sexual dysfunction and satisfaction in women treated for breast cancer. METHODS: A sample was selected of women aged between 18 and 65 who had had surgery for breast cancer, completed neoadjuvant/adjuvant chemotherapy treatment and could be receiving adjuvant hormonal treatment, with an active sex life at least 3 months before starting treatment. Metastatic disease was excluded. A questionnaire structured in 4 dimensions was developed. The MOS SF-12 and QLQ-BR23 questionnaires were also provided. The following metric properties were evaluated: item analysis; internal consistency; temporal stability; construct validity; concurrent, convergent and divergent validity; and feasibility. RESULTS: Three samples were recruited: a pilot sample of 20; a reduction sample of 152; and a validation sample of 148. The presence of 6 dimensions was confirmed: 1) Loss of sex drive; 2) worsening of body image; 3) psychological coping; 4) discomfort during intercourse; 5) satisfaction with sexual relations; and 6) satisfaction with breast reconstruction. Good goodness-of-fit statistics were obtained (χ2/df = 1.5, GFI = 0.9, AGFI = 0.84, CFI = 0.959, RMSEA = 0.062). Reliability was good (α = 0.855), as was test-retest stability (r = 0.838). The correlation with the convergent questionnaires proved to be higher than that obtained with generic measurements. CONCLUSIONS: We were able to develop a short questionnaire (17 items) capable of measuring sexual satisfaction in women with breast cancer with good metric properties.

Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study.

PURPOSE: GEICAM/2006-10 compared anastrozole (A) versus fulvestrant plus anastrozole (A + F) to test the hypothesis of whether a complete oestrogen blockade is superior to aromatase inhibitors alone in breast cancer patients receiving hormone adjuvant therapy. METHODS: Multicenter, open label, phase III study. HR+/HER2- EBC postmenopausal patients were randomized 1:1 to adjuvant A (5 years [year]) or A + F (A plus F 250 mg/4 weeks for 3 year followed by 2 year of A). Stratification factors: prior chemotherapy (yes/no); number of positive lymph nodes (0/1-3/≥ 4); HR status (both positive/one positive) and site. PRIMARY OBJECTIVE: disease-free survival (DFS). Planned sample size: 2852 patients. RESULTS: The study has an early stop due to the financer decision with 870 patients (437 randomized to A and 433 to A + F). Patient characteristics were well balanced. After a median follow-up of 6.24y and 111 DFS events (62 in A and 49 in A + F) the Hazard Ratio for DFS (combination vs. anastrozole) was 0.84 (95% CI 0.58-1.22; p = 0.352). The proportion of patients disease-free in arms A and A + F at 5 year and 7 year were 90.8% versus 91% and 83.6% versus 86.7%, respectively. Most relevant G2-4 toxicities (≥ 5% in either arm) with A versus A + F were joint pain (14.7%; 13.7%), fatigue (2.5%; 7.2%), bone pain (3%; 6.5%), hot flushes (3.5%; 5%) and muscle pain (2.8%; 5.1%). CONCLUSIONS: The GEICAM/2006-10 study did not show a statistically significant increase in DFS by adding adjuvant F to A, though no firm conclusions can be drawn because of the limited sample size due to the early stop of the trial. ClinicalTrials.gov: NCT00543127.

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.

Overeating, caloric restriction and breast cancer risk by pathologic subtype: the EPIGEICAM study.

This study analyzes the association of excessive energy intake and caloric restriction with breast cancer (BC) risk taking into account the individual energy needs of Spanish women. We conducted a multicenter matched case-control study where 973 pairs completed lifestyle and food frequency questionnaires. Expected caloric intake was predicted from a linear regression model in controls, including calories consumed as dependent variable, basal metabolic rate as an offset and physical activity as explanatory. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. The association with BC risk, overall and by pathologic subtype, was evaluated using conditional and multinomial logistic regression models. While premenopausal women that consumed few calories (>20% below predicted) had lower BC risk (OR = 0.36; 95% CI = 0.21-0.63), postmenopausal women with an excessive intake (≥40% above predicted) showed an increased risk (OR = 2.81; 95% CI = 1.65-4.79). For every 20% increase in relative (observed/predicted) caloric intake the risk of hormone receptor positive (p-trend < 0.001) and HER2+ (p-trend = 0.015) tumours increased 13%, being this figure 7% for triple negative tumours. While high energy intake increases BC risk, caloric restriction could be protective. Moderate caloric restriction, in combination with regular physical activity, could be a good strategy for BC prevention.

Long-term response to first-line bevacizumab-based therapy in patients with metastatic breast cancer: results of the observational "LORENA" study.

BACKGROUND: Randomized controlled trials of the first-line combination of bevacizumab and chemotherapy in patients with metastatic breast cancer (MBC) have shown improvements in tumor response and progression-free survival (PFS). OBJECTIVE: The aim of this ambispective, observational study (LORENA) was to describe the clinical characteristics of long-term responders to bevacizumab-based therapy. PATIENTS AND METHODS: This study consisted of a retrospective and a prospective phase. During the retrospective phase, patients with HER2-negative MBC who were treated with bevacizumab-based first-line therapy were included. During the prospective phase, patients with PFS of ≥12 months were treated according to routine clinical practice procedures. Overall survival (OS) and PFS were estimated using the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed. RESULTS: In total, 148 women were included (median age: 50 years; range: 29-81 years). The mean duration of exposure to bevacizumab was 18 months. The majority of patients experienced objective response (complete: 23%; partial: 57%). Median PFS was 22.7 months and median OS was 58.2 months. In multivariate analyses, patients receiving maintenance hormonal therapy (MHT) had longer PFS (P=0.002; hazard ratio [HR] =1.8) and OS (P=0.009; HR=2.0), while patients not previously treated with taxanes had longer OS (P<0.0001; HR =3.3). No unexpected adverse events were observed. CONCLUSION: The results of this study suggest, that among long-term responders, first-line bevacizumab-based therapy is more effective in patients who had not been previously treated with taxanes, and that MHT provides additional therapeutic benefits by extending PFS and OS.