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Optimizations are expected in the development of immunotherapy for the treatment of Triple-negative breast cancer (TNBC). We studied the expression of galectin-9 (Gal-9) after irradiation and assessed the differential impacts of its targeting with or without radiotherapy. Tumor resections from TNBC patients who received neoadjuvant radiotherapy revealed higher levels of Gal-9 in comparison to their baseline level, only in non-responder patients. Gal-9 expression was also found to be increased in TNBC tumor biopsies and cell lines after irradiation. We investigated the therapeutic advantage of targeting Gal-9 after radiotherapy in mice. Irradiated 4T1 cells or control non-irradiated 4T1 cells were injected into BALB/c mice. Anti-Gal-9 antibody treatment decreased tumor progression only in mice injected with irradiated 4T1 cells. This proof-of-concept study demonstrates that Gal-9 could be considered as a dynamic biomarker after radiotherapy for TNBC and suggests that Gal-9 induced-overexpression could represent an opportunity to develop new therapeutic strategies for TNBC patients.
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Skin damage is the most common and most important toxicity during and after radiation therapy (RT). Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients irradiated for an early breast cancer. CANTO is a prospective clinical cohort study of 10 150 patients with stage I-III BC treated from 2012 to 2017 in 26 cancer centres. In our study, we used CANTO-RT, a subcohort of CANTO, including 3480 patients who received RT. We are focus on specific skin toxicities: erythema, fibrosis, telangiectasia and cutaneous pigmentation. The prevalence of toxicities of interest varied over time, so at baseline for early toxicity Month (M) 0-3-6, 41.1% of patients had erythema while 24.8% of patients had fibrosis. At M12 and M36, the prevalence of erythema decreased, respectively, while fibrosis remains stable. The prevalence of telangiectasia increases from 1% to 7.1% from M0-3-6 to M36. After adjustments, we showed an association between the occurrence of skin erythema and obesity; the type of surgery; the presence of axillary dissection; the use of taxane-based CT and the 3D vs IMRT irradiation technique. Regarding fibrosis, an association is found, at M0-3-6, with age at diagnosis, obesity, tobacco and the use of boost. Only obesity and the type of surgery received by the patient remained statistically significant at M12 and M36. In our study we identified several risk factors for acute and late skin reactions. The use of a boost was mainly related to the occurrence of fibrosis while the use of IMRT-type technique decreased the occurrence of skin erythema.
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Neoplasias de la Mama , Telangiectasia , Neoplasias de la Mama/tratamiento farmacológico , Estudios de Cohortes , Eritema/epidemiología , Eritema/etiología , Femenino , Fibrosis , Humanos , Obesidad/complicaciones , Estudios Prospectivos , Telangiectasia/complicaciones , Telangiectasia/etiologíaRESUMEN
OBJECTIVE: To determine the possible effect of two homeopathic medicines, Ruta graveolens 5CH and Rhus toxicodendron 9CH, in the prevention of aromatase inhibitor (AI) associated joint pain and/or stiffness in women with early, hormone-receptor positive, breast cancer. METHODS: This prospective, unrandomized observational study was carried out between April and October 2014. Women were recruited in two groups, according to which of the two study centres they attended: one receiving homeopathy in addition to standard treatment (group H) and a control group, receiving standard treatment (group C). All women were treated with an AI. In addition, women in group H also took Ruta graveolens 5CH and Rhus toxicodendron 9CH (5 granules, twice a day) up to 7 days before starting AI treatment. The homeopathic medicines were continued for 3 months. Demographic and clinical data were recorded using a self-assessment questionnaire at inclusion (T0) and 3 months (T3). Primary evaluation criteria were the evolution of scores for joint pain and stiffness, the impact of pain on sleep and analgesic consumption in the two groups after 3 months of treatment. RESULTS: Forty patients (mean age 64.9±8.1 years) were recruited, 20 in each group. Two-thirds of the patients had joint pain before starting AI treatment. There was a significant difference in the evolution of mean composite pain score between T0 and T3 in the two groups (-1.3 in group H vs. +3.4 in group C; p=0.0001). The individual components of the pain score (frequency, intensity and number of sites of pain) also decreased significantly in group H. Nine patients in group C (45%) vs. 1 (5%) in group H increased their analgesic consumption between T0 and T3 (p=0.0076). After 3 months of treatment, joint pain had a worse impact on sleep in patients in group C (35% vs. 0% of patients; p=0.0083). The differences observed in the evolution of morning and daytime stiffness between the two groups were smaller (p=0.053 and p=0.33, respectively), with the exception of time necessary for the disappearance of morning stiffness which was greater in group C (37.7±23.0 vs. 17.9±20.1 min; p=0.0173). CONCLUSION: These preliminary results suggest that treatment with Ruta graveolens 5CH and Rhus toxicodendron 9CH may decrease joint pain/stiffness in breast cancer patients treated with AIs. A larger-scale randomized study is required to confirm these results.
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Inhibidores de la Aromatasa/efectos adversos , Artralgia/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Homeopatía , Fitoterapia , Ruta/química , Toxicodendron/química , Anciano , Anciano de 80 o más Años , Analgésicos/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , SueñoRESUMEN
This article describes the methodology used and provides a characterization of the study population in CANTO-RT (CANcer TOxicities RadioTherapy). CANTO (NCT01993498) is a prospective clinical cohort study including patients with stage I-III BC from 26 French cancer centers. Patients matching all CANTO inclusion and exclusion criteria who received RT in one of the 10 top recruiting CANTO centers were selected. Individual full DICOM RT files were collected, pseudo-anonymized, structured and analyzed on the CANTO-RT/UNITRAD web platform. CANTO-RT included 3875 BC patients with a median follow-up of 64 months. Among the 3797 patients with unilateral RT, 3065 (80.4%) had breast-conserving surgery, and 2712 (71.5%) had sentinel node surgery. Tumor bed boost was delivered in 2658 patients (68.5%) and lymph node RT in 1356 patients (35%), including internal mammary chain in 844 patients (21.8%). Most patients (3691 (95.3%)) were treated with 3D conformal RT. Target volumes, organs at risk contours and dose/volume histograms were extracted after quality-control procedures. CANTO-RT is one of the largest early BC prospective cohorts with full individual clinical, biological, imaging and DICOM RT data available. It is a valuable resource for the identification and validation of clinical and dosimetric predictive factors of RT and multimodal treatment-related toxicities.
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PURPOSE: This economic evaluation reports the incremental cost-utility ratio and national budget impact in France of accelerated partial breast irradiation (APBI) vs standard or hypofractionated whole breast irradiation (WBI) in breast cancer patients at low risk of local recurrence. MATERIALS AND METHODS: We compared 490 women randomized to the APBI (ten fractions delivered twice daily over one week) with 488 women in the WBI arm (one fraction per day delivered five days per week over three or six weeks). We took the perspective of the French national health insurance with a three-year time horizon. The outcome was quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio was estimated and uncertainty was explored by probabilistic bootstrapping. Transportation and sick leave costs were added in a sensitivity analysis and a national budget impact analysis based on the incidence of breast cancer estimates in France performed. RESULTS: At three years, the average cost per patient was 2,549 (±1,954) in the APBI arm and 4,468 (±1,586) in the WBI arm (p-value < 0.001), radiotherapy was the main driver of the difference between the two arms. No significant difference was found in QALYs. For an average of 60,000 new cases of breast cancer diagnosed annually in France, 28,000 would be eligible for treatment with APBI. A 100% uptake of APBI would result in a yearly30 million cost saving. CONCLUSION: APBI for the treatment of postmenopausal women with early-stage breast cancer is cost saving, with no difference in outcome measured by QALYs.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/cirugía , Análisis Costo-Beneficio , Posmenopausia , Mastectomía Segmentaria , FranciaRESUMEN
BACKGROUND: Fatigue is a common and disabling symptom after breast cancer (BC) treatment, significantly impacting patients' quality of life. We aimed to assess the impact of radiation therapy (RT) modalities on fatigue one year after treatment among patients with early-stage BC. METHODS: We used CANTO-RT, a subcohort of CANcer TOxicity (CANTO; NCT01993498), a multicentric nationwide prospective cohort of stages I-III BC treated from 2012 to 2017. Our primary outcome was severe global fatigue 1 year after RT completion (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 score ≥40/100). The secondary outcomes included severe physical, emotional and cognitive fatigue (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-FA12). RT-related variables were used as independent variables. Multivariable logistic regression models assessed associations between RT-related variables and fatigue. RESULTS: The final analytic cohort included 3295 patients. The prevalence of severe global fatigue 1 year after treatment was 33.3%. Internal mammary chain RT (adjusted odds ratio [OR] 1.48 [95% confidence interval [CI] 1.03-2.13; p = 0.0355]) and normofractionated RT (adjusted OR 1.88 [95% CI 1.06-3.31; p = 0.0298]) were associated with increased odds of severe global fatigue. In addition, there was a significant association between normofractionated RT (adjusted OR 1.849 [95% CI 1.04-3.3; p = 0.0354]) and an increased likelihood of severe physical fatigue. CONCLUSION: We found a significant association between internal mammary chain RT (versus No), normofractionated RT (versus hypofractionated RT) and increased likelihood of persistent severe global fatigue. Our data add to the current understanding of treatment-related factors affecting fatigue after BC and could lead to personalised interventions to improve the prevention and management of this disabling symptom.
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Neoplasias de la Mama , Supervivientes de Cáncer , Humanos , Femenino , Neoplasias de la Mama/terapia , Calidad de Vida , Estudios Prospectivos , MamaRESUMEN
Pemphigus is a serious and rare chronic bullous autoimmune disease. It is characterized by mucocutaneous erosions secondary to autoantibodies directed against desmogleins 1 and 3, proteins involved in intercellular adhesion mechanisms. The occurrence of pemphigus is based on the triggering of genetic and external environmental factors such as drugs, infection, and more rarely radiotherapy. To date, only 16 cases of radiation-induced pemphigus are described in the context of breast cancer treatment. We present the case of a 76-year-old woman who had a recurrence of pemphigus vulgaris limited to the irradiation field after exposure to an adjuvant radiotherapy treatment for a bilateral triple-negative breast cancer. The onset was bilateral limited to the irradiation area and was treated effectively with local and systemic corticosteroids. After a rigorous review of the literature, only 16 cases of breast cancer radiation-induced pemphigus appeared. In contrast to several cases, the rash was limited to the irradiated area and improved with systemic corticosteroids. For more than three-quarters of the described cases in the literature, pemphigus occurs within 3 months following the end of treatment. After systemic immunosuppressive treatment, this disease disappears in the vast majority of the reported cases.
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PURPOSE: To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS: The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p < 0.001), grade ≥2 dermatitis (2.8% vs. 0.7%, p < 0.001), and grade 2 hyperpigmentation (6.9% vs. 3.6%, p = 0.005) were more frequent in arm B than arm A. No acute lung or cardiac toxicity was observed. Smoking history, large breast size, and large breast CTV were strong predictive factors of grade ≥2 acute skin toxicities. CONCLUSIONS: The QA program showed deviations in breast and tumor bed delineation. The boost significantly increased acute skin toxicities.
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Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Mama , Neoplasias de la Mama/radioterapia , Femenino , Humanos , Hipertrofia , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Cancer has become a major public health issue. It is thus crucial to measure the general population's behaviours, opinions and perceptions about cancer and its associated risk factors. This article describes some of the main findings of a 2005 French survey (n = 4,046). Cancer is considered by a large majority to be the most serious disease, far before HIV/AIDS and cardiovascular diseases. The carcinogenic risk that is associated to main risk factors, such as sun exposure, tobacco-smoking and alcohol use appears to be well-known. However, many people justify dangerous behaviours with strongly-anchored beliefs, which maintain dangerous behaviours for health on the long-term. What's more, the perception of risk proliferation can also generate risk denial. Because self-exempting beliefs are still widespread within the general opinion, it is essential to continue public health information campaigns dedicated to cancer prevention, so as to induce better prevention practices within the general population and to reduce stigmatisation and isolation experienced by cancer patients. If risk denial is not systematically a consequence of a lack of information, it is generally associated to a cognitive construction that gives coherence to behaviours.
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Conocimientos, Actitudes y Práctica en Salud , Neoplasias/psicología , Opinión Pública , Adolescente , Adulto , Anciano , Consumo de Bebidas Alcohólicas/efectos adversos , Carcinógenos Ambientales , Cultura , Negación en Psicología , Francia , Agencias Gubernamentales , Conductas Relacionadas con la Salud , Humanos , Persona de Mediana Edad , Neoplasias/etiología , Neoplasias/prevención & control , Factores de Riesgo , Asunción de Riesgos , Muestreo , Fumar/efectos adversos , Luz Solar/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Past studies on smokers' risk perception have produced mixed results. We endorsed a new approach to assess smokers' perceptions of risk by asking them to estimate threshold values for the cancer risk associated with daily consumption of tobacco and number of smoking years. We expected that many smokers would endorse a "risk denial" attitude, with threshold estimates higher than their own smoking consumption and duration. METHODOLOGY: A French national telephone survey (n = 3820; 979 current smokers) included several questions about smoking behaviours and related beliefs. RESULTS: Among current smokers, 44% considered that smoking can cause cancer only for a daily consumption higher than their own consumption, and an additional 20% considered that the cancer risk becomes high only for a smoking duration higher than their own. Most smokers also agreed with other "risk denial" statements ("smoking is not more dangerous than air pollution," "some people smoke their whole life but never get sick"). Those who considered they smoked too few cigarettes to be at risk were less likely to report personal fear of smoking related cancer. CONCLUSION: Risk denial is quite widespread among smokers and does not simply reflect a lack of information about health risks related to tobacco. Fully informing smokers about their risks may necessitate changing the way they process information to produce beliefs and limiting their capacity to generate self exempting beliefs.
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Negación en Psicología , Conocimientos, Actitudes y Práctica en Salud , Fumar/efectos adversos , Fumar/psicología , Adolescente , Adulto , Miedo , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/etiología , Neoplasias/psicología , Medición de Riesgo , Cese del Hábito de Fumar/psicología , Factores de TiempoRESUMEN
OBJECTIVE: The goal of this study was to examine the association between sexual abuse (SA) and initiation, cessation, and current cigarette smoking among a large representative adult population in France. METHOD: A random sample size of 12,256 adults (18-75 years of age) was interviewed by telephone concerning demographic variables, health practices and beliefs, and health status--for which SA and tobacco questions were included. Bivariate and multivariate analyses were conducted. RESULTS: Nearly 46% of SA survivors were current smokers compared to 34% of non-abused persons (p<.001). Survivors of SA consumed more cigarettes per day than non-abused individuals (14.5 vs. 12.4, p<.01). Survival analysis showed an increased risk of smoking initiation for respondents abused before 18 (adjusted relative hazard=1.55; p<.0001) with referent to the non-abused group. SA was not found to be a significant predictor of current smoking status among those who began smoking after the first incident of SA. Respondents who were not sexually abused were 1.8 times (95% CI, 1.12-2.99) more likely to quit smoking than people who began smoking after they were sexually abused. CONCLUSIONS: The early identification and treatment of sexually abused persons is critical to decrease smoking among adolescents and adults because of the association of SA with both smoking initiation and decreased cessation rates. It may be more difficult to detect an association between SA and current smoking due to the high rates of smoking and lower rates of quitting among the general French population.
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Abuso Sexual Infantil/estadística & datos numéricos , Cese del Hábito de Fumar/métodos , Prevención del Hábito de Fumar , Fumar/epidemiología , Adolescente , Adulto , Anciano , Áreas de Influencia de Salud , Femenino , Francia/epidemiología , Humanos , Masculino , Tamizaje Masivo/métodos , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
The aim of this study was to assess the short-term reproducibility and the validity of reported ETS (environmental tobacco smoke) exposure, with a special emphasis on the potential misclassification related to personal or family history of asthma. Analyses were based on the data on the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA), a case-control study of asthma that included first degree relatives of asthmatic cases. The study was comprised of 348 families of asthmatics recruited in six chest clinics throughout France and 416 population-based controls. For studying the validity of ETS reports, personal active smoking histories reported by family members were taken as reference. The reproducibility of ETS exposure report was good, and independent of asthma. The validity of the report of maternal and paternal smoking in childhood and spouse smoking during life was high (overall agreement > or = 84%). Mothers of asthmatic children significantly underreported their smoking habits when questioned on their children's passive tobacco exposure. Offspring of parents who had stopped smoking underestimated their ETS exposure in childhood. In conclusion, interviews with mothers on their personal active smoking habits may provide a more accurate estimate of their asthmatic child's passive exposure than asking mothers specifically about their children's passive exposure. There was no indication that asthma status (either of the parent/spouse or of the respondent) by itself influences the report of ETS exposure during childhood or adulthood.