Calidad de vida en cáncer de mama metastásico de larga evolución: La opinión de las pacientes

Metastasic breast cancer patients live longer thanks to the lasts improvements in their treatment. Nonetheless, there exist few studies focused on the quality of live (QoL) of those patients. The aim of our study is to improve the knowledge of metastatic breast cancer patient’s quality of life, for this purpose we have elaborated an open questionnaire as a complement to the QoL tests available. Material and methods: From June 2011 to February 2012 we conducted 24 interviews with a questionnaire based on medical and psychosocial items. Results: 58% of patients considered that treatment improved their QoL, an 83.3% expressed that the benefit of the treatment compensated for the secondary effects, complementary tests give them relieve, control over the illness and information. Only two thirds of those patients expressed to have social support, and one third said to share their grief with nobody. The main concerns expressed by the patients were in order of value: their family, loss of self-caring, fear about the future and to the illness progression. Half of the patients think that the disease has brought some value to their lives such as improving their scale of values and to improve empathy to somebody else’s problems. Conclusion: Metastatic breast cancer patient’s attitude is admirable in the way they are adapted to such a wearing situation. Nonetheless it’s imperative to offer them the help and the medical information they need to compensate for their solitude in front of the illness.La supervivencia de las pacientes diagnosticadas de cáncer de mama metástasico ha aumentado en los últimos años gracias a la mejora en los tratamientos. Con todo hay pocos estudios que evalúen la calidad de vida en esta situación. El objetivo de nuestro estudio es mejorar el conocimiento sobre la calidad de vida de estas pacientes complementando la información obtenida en los cuestionarios de calidad de vida existentes con una entrevista de preguntas abiertas. Material y métodos: entre junio de 2011 y febrero 2012 se realizaron un total de 24 entrevistas con un cuestionario basado en preguntas de carácter médico y de carácter psicosocial. Resultados: un 58% de las pacientes opinan que el tratamiento mejora la calidad de vida y un 83,3% que los efectos secundarios compensan frente al beneficio de la quimioterapia; las exploraciones complementarias les dan seguridad. Únicamente dos tercios de las pacientes manifiestan tener apoyo social y un tercio no comparte el malestar con nadie. Los aspectos de la enfermedad que más les cuesta afrontar son en orden de importancia: la familia, la pérdida de autonomía, el miedo a la incertidumbre y la progresión de la enfermedad. La mitad de las pacientes opinan que la enfermedad ha aportado un valor positivo en sus vidas. Conclusión: la actitud de las pacientes metastásicas de larga evolución es admirable, por lo bien adaptadas que están a la situación. No obstante, recomendamos poder ofrecerles el apoyo y la información que necesitan para compensar la sensación de soledad frente a la enfermedad

Calidad de vida en cáncer de mama metastásico de larga evolución : la opinión de las pacientes

La supervivencia de las pacientes diagnosticadas de cáncer de mama metástasico ha aumentado en los últimos años gracias a la mejora en los tratamientos. Con todo hay pocos estudios que evalúen la calidad de vida en esta situación. El objetivo de nuestro estudio es mejorar el conocimiento sobre la calidad de vida de estas pacientes complementando la información obtenida en los cuestionarios de calidad de vida existentes con una entrevista de preguntas abiertas. Material y métodos: entre junio de 2011 y febrero 2012 se realizaron un total de 24 entrevistas con un cuestionario basado en preguntas de carácter médico y de carácter psicosocial. Resultados: un 58% de las pacientes opinan que el tratamiento mejora la calidad de vida y un 83,3% que los efectos secundarios compensan frente al beneficio de la quimioterapia; las exploraciones complementarias les dan seguridad. Únicamente dos tercios de las pacientes manifiestan tener apoyo social y un tercio no comparte el malestar con nadie. Los aspectos de la enfermedad que más les cuesta afrontar son en orden de importancia: la familia, la pérdida de autonomía, el miedo a la incertidumbre y la progresión de la enfermedad. La mitad de las pacientes opinan que la enfermedad ha aportado un valor positivo en sus vidas. Conclusión: la actitud de las pacientes metastásicas de larga evolución es admirable, por lo bien adaptadas que están a la situación. No obstante, recomendamos poder ofrecerles el apoyo y la información que necesitan para compensar la sensación de soledad frente a la enfermedadMetastasic breast cancer patients live longer thanks to the lasts improvements in their treatment. Nonetheless, there exist few studies focused on the quality of live (QoL) of those patients. The aim of our study is to improve the knowledge of metastatic breast cancer patient's quality of life, for this purpose we have elaborated an open questionnaire as a complement to the QoL tests available. Material and methods: From June 2011 to February 2012 we conducted 24 interviews with a questionnaire based on medical and psychosocial items. Results: 58% of patients considered that treatment improved their QoL, an 83.3% expressed that the benefit of the treatment compensated for the secondary effects, complementary tests give them relieve, control over the illness and information. Only two thirds of those patients expressed to have social support, and one third said to share their grief with nobody. The main concerns expressed by the patients were in order of value: their family, loss of self-caring, fear about the future and to the illness progression. Half of the patients think that the disease has brought some value to their lives such as improving their scale of values and to improve empathy to somebody else's problems. Conclusion: Metastatic breast cancer patient's attitude is admirable in the way they are adapted to such a wearing situation. Nonetheless it's imperative to offer them the help and the medical information they need to compensate for their solitude in front of the illnes

Real-world efficacy and safety of eribulin in advanced and pretreated HER2-negative breast cancer in a Spanish comprehensive cancer center

Background Eribulin improves survival in pre-treated HER2-negative advanced breast cancer (ABC). However, limited data exist on co-morbidities and central nervous system (CNS) efficacy. The purpose of this study was to review eribulin's efficacy and safety in everyday clinical practice with special focus on age, body mass index (BMI) and central nervous system (CNS) activity. Methods An observational study was conducted in a series of HER2-negative ABC patients treated from January'14-December'17 outside a clinical trial. Objective Response Rate (ORR), Progression Free Survival (PFS), Overall Survival (OS), and association of clinical and pathological variables with outcome were evaluated. Results Ninety-five women were treated with at least one cycle of eribulin. Median age was 57 (33-83), and 18% were obese. Median number of prior chemotherapies for ABC was 3 (2-5) and 76% of patients had visceral metastases, including 21% with CNS involvement. Most tumors were estrogen receptor-positive (79%). ORR and stable disease (SD) at 6 months were 26.2 and 37.5%, respectively. Remarkably, relevant CNS efficacy was observed with eribulin: 20% of patients obtained partial response and 25% SD. Treatment was generally well tolerated and manageable, with 29% grade 3 and 10.9% grade 4 toxicities. Median PFS and OS were 4.1 months (CI95% 3.2-4.9) and 11.1 months (CI95% 9.5-14.7), respectively. Triple-negative disease, > 2organs involved and being younger than 70 years old were independent prognosis factors for worse OS in multivariate analysis. Most patients (75%) progressed in pre-existing metastases sites. Conclusion In everyday clinical practice, eribulin's efficacy seems similar to pivotal trials. CNS-efficacy was observed. TNBC, > 2 organs involved and being younger than 70 years old were independent prognosis factors for worse OS. Remarkably, less incidence of grade 4-toxicity compared to previous studies was found

Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells

Traditionally, studies to address the characterization of mechanisms promoting tumor aggressiveness and progression have been focused only on primary tumor analyses, which could provide relevant information but have limitations to really characterize the more aggressive tumor population. To overcome these limitations, circulating tumor cells (CTCs) represent a noninvasive and valuable tool for real-time profiling of disseminated tumor cells. Therefore, the aim of the present study was to explore the value of CTC enumeration and characterization to identify markers associated with the outcome and the aggressiveness of triple-negative breast cancer (TNBC). For that aim, the CTC population from 32 patients diagnosed with TNBC was isolated and characterized. This population showed important cell plasticity in terms of expression of epithelia/mesenchymal and stemness markers, suggesting the relevance of epithelial to mesenchymal transition (EMT) intermediate phenotypes for efficient tumor dissemination. Importantly, the CTC signature demonstrated prognostic value to predict the patients' outcome and pointed to a relevant role of tissue inhibitor of metalloproteinases 1 (TIMP1) and androgen receptor (AR) for TNBC biology. Furthermore, we also analyzed the usefulness of the AR and TIMP1 blockade to target TNBC proliferation and dissemination using in vitro and in vivo zebra fish and mouse models. Overall, the molecular characterization of CTCs from advanced TNBC patients identifies highly specific biomarkers with potential applicability as noninvasive prognostic markers and reinforced the value of TIMP1 and AR as potential therapeutic targets to tackle the most aggressive breast cancer

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinelnodes after neoadjuvant therapy (ADARNAT trial)

Introduction: Breast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects. Methods and analyses: This multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival. Discussion: This study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity. Ethics and dissemination: The Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results

Immune Cell Associations with Cancer Risk.

Proper immune system function hinders cancer development, but little is known about whether genetic variants linked to cancer risk alter immune cells. Here, we report 57 cancer risk loci associated with differences in immune and/or stromal cell contents in the corresponding tissue. Predicted target genes show expression and regulatory associations with immune features. Polygenic risk scores also reveal associations with immune and/or stromal cell contents, and breast cancer scores show consistent results in normal and tumor tissue. SH2B3 links peripheral alterations of several immune cell types to the risk of this malignancy. Pleiotropic SH2B3 variants are associated with breast cancer risk in BRCA1/2 mutation carriers. A retrospective case-cohort study indicates a positive association between blood counts of basophils, leukocytes, and monocytes and age at breast cancer diagnosis. These findings broaden our knowledge of the role of the immune system in cancer and highlight promising prevention strategies for individuals at high risk

Lymphangioleiomyomatosis biomarkers linked to lung metastatic potential and cell stemness

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-ß3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM

Axillary lymph node dissection versus radiotherapy in breast cancer with positive sentinel nodes after neoadjuvant therapy (ADARNAT trial)

IntroductionBreast cancer surgery currently focuses on de-escalating treatment without compromising patient survival. Axillary radiotherapy (ART) now replaces axillary lymph node dissection (ALND) in patients with limited sentinel lymph node (SLN) involvement during the primary surgery, and this has significantly reduced the incidence of lymphedema without worsening the prognosis. However, patients treated with neoadjuvant systemic treatment (NST) cannot benefit from this option despite the low incidence of residual disease in the armpit in most cases. Data regarding the use of radiotherapy instead of ALND in this population are lacking. This study will assess whether ART is non-inferior to ALND in terms of recurrence and overall survival in patients with positive SLN after NST, including whether it reduces surgery-related adverse effects.Methods and analysesThis multicenter, randomized, open-label, phase 3 trial will enroll 1660 patients with breast cancer and positive SLNs following NST in approximately 50 Spanish centers over 3 years. Patients will be stratified by NST regimen and nodal involvement (isolated tumoral cells or micrometastasis versus macrometastasis) and randomly assigned 1:1 to ART without ALND (study arm) or ALND alone (control arm). Level 3 and supraclavicular radiotherapy will be added in both arms. The primary outcome is the 5-year axillary recurrence determined by clinical and radiological examination. The secondary outcomes include lymphedema or arm dysfunction, quality of life based (EORTC QLQ-C30 and QLQ-BR23 questionnaires), disease-free survival, and overall survival.DiscussionThis study aims to provide data to confirm the efficacy and safety of ART over ALND in patients with a positive SLN after NST, together with the impact on morbidity.Ethics and disseminationThe Research Ethics Committee of Bellvitge University Hospital approved this trial (Protocol Record PR148/21, version 3, 1/2/2022) and all patients must provide written informed consent. The involvement of around 50 centers across Spain will facilitate the dissemination of our results.Trial registrationClinicalTrials.gov, identifier number NCT04889924

Calidad de vida en cáncer de mama metastásico de larga evolución : la opinión de las pacientes

La supervivencia de las pacientes diagnosticadas de cáncer de mama metástasico ha aumentado en los últimos años gracias a la mejora en los tratamientos. Con todo hay pocos estudios que evalúen la calidad de vida en esta situación. El objetivo de nuestro estudio es mejorar el conocimiento sobre la calidad de vida de estas pacientes complementando la información obtenida en los cuestionarios de calidad de vida existentes con una entrevista de preguntas abiertas. Material y métodos: entre junio de 2011 y febrero 2012 se realizaron un total de 24 entrevistas con un cuestionario basado en preguntas de carácter médico y de carácter psicosocial. Resultados: un 58% de las pacientes opinan que el tratamiento mejora la calidad de vida y un 83,3% que los efectos secundarios compensan frente al beneficio de la quimioterapia; las exploraciones complementarias les dan seguridad. Únicamente dos tercios de las pacientes manifiestan tener apoyo social y un tercio no comparte el malestar con nadie. Los aspectos de la enfermedad que más les cuesta afrontar son en orden de importancia: la familia, la pérdida de autonomía, el miedo a la incertidumbre y la progresión de la enfermedad. La mitad de las pacientes opinan que la enfermedad ha aportado un valor positivo en sus vidas. Conclusión: la actitud de las pacientes metastásicas de larga evolución es admirable, por lo bien adaptadas que están a la situación. No obstante, recomendamos poder ofrecerles el apoyo y la información que necesitan para compensar la sensación de soledad frente a la enfermedadMetastasic breast cancer patients live longer thanks to the lasts improvements in their treatment. Nonetheless, there exist few studies focused on the quality of live (QoL) of those patients. The aim of our study is to improve the knowledge of metastatic breast cancer patient's quality of life, for this purpose we have elaborated an open questionnaire as a complement to the QoL tests available. Material and methods: From June 2011 to February 2012 we conducted 24 interviews with a questionnaire based on medical and psychosocial items. Results: 58% of patients considered that treatment improved their QoL, an 83.3% expressed that the benefit of the treatment compensated for the secondary effects, complementary tests give them relieve, control over the illness and information. Only two thirds of those patients expressed to have social support, and one third said to share their grief with nobody. The main concerns expressed by the patients were in order of value: their family, loss of self-caring, fear about the future and to the illness progression. Half of the patients think that the disease has brought some value to their lives such as improving their scale of values and to improve empathy to somebody else's problems. Conclusion: Metastatic breast cancer patient's attitude is admirable in the way they are adapted to such a wearing situation. Nonetheless it's imperative to offer them the help and the medical information they need to compensate for their solitude in front of the illnes

PAM50 Subtypes in Baseline and Residual Tumors Following Neoadjuvant Trastuzumab-Based Chemotherapy in HER2-Positive Breast Cancer: A Consecutive-Series From a Single Institution

Introduction: HER2-enriched subtype has been associated with higher response to neoadjuvant anti-HER2-based therapy across various clinical trials. However, limited data exist in real-world practice and regarding residual disease. Here, we evaluate the association of HER2-enriched with pathological response (pCR) and gene expression changes in pre- and post-treatment paired samples in HER2-positive breast cancer patients treated outside of a clinical trial. Methods: We evaluated clinical-pathological data from a consecutive series of 150 patients with stage II-IIIC HER2-positive breast cancer treated from August 2004 to December 2012 with trastuzumab-based neoadjuvant chemotherapy. Expression of 105 breast cancer-related genes, including the PAM50 genes, was determined in available pre-and post-treatment formalin-fixed paraffin-embedded tumor samples using the nCounter platform. Intrinsic molecular subtypes were determined using the research-based PAM50 predictor. Association of genomic variables with total pCR was performed. Results: The pCR rate was 53.3%, with higher pCR among hormonal receptor (HR)-negative tumors (70 vs. 39%; P < 0.001). A total of 89 baseline and 28 residual tumors were profiled, including pre- and post-treatment paired samples from 26 patients not achieving a pCR. HER2-enriched was the predominant baseline subtype not only in the overall and HR-negative cohorts (64 and 75%, respectively), but also in the HR-positive cohort (55%). HER2-enriched was associated with higher pCR rates compared to non-HER2-enriched subtypes (65 vs. 31%; OR = 4.07, 95% CI 1.65-10.61, P < 0.002) and this association was independent of HR status. In pre- and post-treatment paired samples from patients not achieving a pCR, a lower proportion of HER2-enriched and twice the number of luminal tumors were observed at baseline, and luminal A was the most frequent subtype in residual tumors. Interestingly, most (81.8%) HER2-enriched tumors changed to non-HER2-enriched, whereas most luminal A samples maintained the same subtype in residual tumors. Conclusions: Outside of a clinical trial, PAM50 HER2-enriched subtype predicts pCR beyond HR status following trastuzumab-based chemotherapy in HER2-positive disease. The clinical value of intrinsic molecular subtype in residual disease warrants further investigation