ABSTRACT
CONTEXT: In France, 2300 adolescents and young adults (AYAs, 15-25 years old) are diagnosed with cancer each year. As soon as the disease is diagnosed, a number of physical, psychological and social needs may arise. The aim of this study is to develop a tool to measure unmet needs that will allow the specificities of AYAs to be understood while allowing health care staff to mobilise the necessary actors to resolve them. METHODS: We developed the Questionnaire nEEd Cancer AYAs (QUEEC-AYAs questionnaire), from two existing questionnaires: the Cancer Needs Questionnaire Young People and the Needs Assessment & Service Bridge. A main sample of 103 AYAs then received and completed the questionnaire in order to conduct an exploratory factor analysis. RESULTS: The final structure of the QUEEC-AYAs is composed of 7 dimensions and 48 items: information (8 items), cancer care team (6 items), Physical health (4 items), Emotional health (14 items), Sexual & reproductive health (6 items), Health behaviors & wellness (4 items), Daily life (6 items). The questionnaire has a good acceptability and all domains have a Cronbach's alphas value above 0.80. CONCLUSION: The QUEEC-AYAs is the first measure of the psychosocial needs of AYAs available in French. Its systematic use in health care services should improve the coordination of care required by AYAs during and after treatment. TRIAL REGISTRATION: This study was approved by the ethics committee of the Paoli-Calmettes Institute (IRB # IPC 2021-041, 2021 May 20).
Subject(s)
Needs Assessment , Neoplasms , Humans , Surveys and Questionnaires , Adolescent , Neoplasms/psychology , Neoplasms/therapy , Young Adult , Female , Male , France , Adult , Psychometrics , Reproducibility of Results , Health Services Needs and Demand , Quality of Life/psychologyABSTRACT
Background: Triple-negative breast cancers (TNBCs) are associated with a poor prognosis. In contrast to other molecular subtypes, they have no identified specific target and chemotherapy remains the only available systemic treatment. The adhesion molecule nectin-4 represents a new potential therapeutic target in different cancer models. Here, we have tested the prognostic value of nectin-4 expression and assessed the therapeutic efficiency of an anti-nectin 4 antibody drug conjugate (ADC) on localised and metastatic TNBC in vitro and in vivo. Materials and methods: We analysed nectin-4/PVRL4 mRNA expression in 5673 invasive breast cancers and searched for correlations with clinicopathological features including metastasis-free survival (MFS). Immunohistochemistry was carried out in 61 TNBCs and in samples of primary TNBC Patient-Derived Xenografts (PDXs). An anti-nectin-4 antibody eligible for ADC was produced and tested in vitro and in vivo in localised and metastatic TNBC PDXs. Results: High nectin-4/PVRL4 mRNA expression was associated with poor-prognosis features including the TN and basal subtypes. High PVRL4 mRNA expression showed independent negative prognostic value for MFS in multivariate analysis in TNBCs. Nectin-4 protein expression was not detected in adult healthy tissues including mammary tissue. Membranous protein expression was found in 62% of TNBCs, with strong correlation with mRNA expression. We developed an ADC (N41mab-vcMMAE) comprising a human anti-nectin-4 monoclonal antibody conjugated to monomethyl auristatin-E (MMAE). In vitro, this ADC bound to nectin-4 with high affinity and specificity and induced its internalisation as well as dose-dependent cytotoxicity on nectin-4-expressing breast cancer cell lines. In vivo, this ADC induced rapid, complete and durable responses on nectin-4-positive xenograft TNBC samples including primary tumours, metastatic lesions, and local relapses; efficiency was dependent on both the dose and the nectin-4 tumour expression level. Conclusion: Nectin-4 is both a new promising prognostic biomarker and specific therapeutic target for ADC in the very limited armamentarium against TNBC.
Subject(s)
Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacology , Biomarkers, Tumor/analysis , Cell Adhesion Molecules/biosynthesis , Triple Negative Breast Neoplasms/metabolism , Adult , Aminobenzoates/pharmacology , Animals , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Immunohistochemistry , Mice , Middle Aged , Neoplasm Metastasis , Oligonucleotide Array Sequence Analysis , Oligopeptides/pharmacology , Prognosis , Triple Negative Breast Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
Background: We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Patients and methods: Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. Results: From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. Conclusion: In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Inflammatory Breast Neoplasms/drug therapy , Inflammatory Breast Neoplasms/pathology , Neoplastic Cells, Circulating/drug effects , Neoplastic Cells, Circulating/pathology , Adult , Aged , Bevacizumab/administration & dosage , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Humans , Inflammatory Breast Neoplasms/blood , Inflammatory Breast Neoplasms/surgery , Middle Aged , Neoadjuvant Therapy , Prognosis , Receptor, ErbB-2/metabolism , Taxoids/administration & dosage , Trastuzumab/administration & dosage , Young AdultABSTRACT
BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5-fluorouracil (D-5FU) regimen after preoperative dose-intense (DI) epirubicin-cyclophosphamide (EC) and locoregional treatment in IBC patients. PATIENTS AND METHODS: PEGASE 07 was a national randomized phase III open-label study involving 14 hospitals in France. Women with nonmetastatic IBC were eligible and randomly assigned to receive either four cycles of DI EC (E 150 mg/m(2) and C 4000 mg/m(2) every 3 weeks with repeated hematopoietic stem cell support), then mastectomy with axillary lymph node dissection, and radiotherapy (arm A) or the same treatment followed by four cycles of D-5FU (D 85 mg/m(2), day 1 and 5FU 750 mg/m(2)/day continuous infusion, days 1-5 every 3 weeks) administered postradiotherapy (arm B). Patients with hormone receptor-positive tumors received hormonal therapy. Disease-free survival (DFS) was the primary end point. Secondary end points included tolerance, pathological complete response (pCR) rate, and overall survival (OS). RESULTS: Between January 2001 and May 2005, 174 patients were enrolled and treated (87 in each arm). Median follow-up was similar in both arms: 59.6 months [95% confidence interval (CI) 58.4-60.3] in arm A and 60.5 months (95% CI 58.3-61.4) in arm B. The estimated 5-year DFS rates were not different: 55% (95% CI 43.9-64.7) in arm A and 55.5% (95% CI 44.3-65.3) in arm B [hazard ratio (HR) = 0.94 (0.61-1.48); P = 0.81]. Identical results were observed for 5-year OS: 70.2% (95% CI 59.1-78.8) in arm A and 70% (95% CI 58.8-78.7) in arm B [HR = 0.93 (0.55-1.60); P = 0.814]. Following DI EC induction, in-breast and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen receptor and pCR status were independently associated with survival. CONCLUSION: The addition of D-5FU after preoperative DI EC and standard local therapy did not improve DFS in IBC. CLINICAL TRIAL NUMBER: ClinicalTrials.gov identifier: NCT02324088.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Inflammatory Breast Neoplasms/drug therapy , Mastectomy , Neoadjuvant Therapy/methods , Adult , Antineoplastic Agents, Hormonal/administration & dosage , Axilla , Chemoradiotherapy, Adjuvant/methods , Chemotherapy, Adjuvant/methods , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Inflammatory Breast Neoplasms/metabolism , Lymph Node Excision , Middle Aged , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Taxoids/administration & dosageABSTRACT
BACKGROUND: Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations. METHODS: Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis. RESULTS: After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS. CONCLUSIONS: Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Combined Modality Therapy , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Epirubicin/adverse effects , Epirubicin/therapeutic use , Female , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Follow-Up Studies , Humans , Immunohistochemistry , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome , Tumor Burden , Young AdultABSTRACT
BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive disease. To date, no molecular feature reliably predicts either the response to chemotherapy (CT) or the survival. Using DNA microarrays, we searched for multigene predictors. PATIENTS AND METHODS: The World IBC Consortium generated whole-genome expression profiles of 137 IBC and 252 non-IBC (nIBC) samples. We searched for transcriptional profiles associated with pathological complete response (pCR) to neoadjuvant anthracycline-based CT and distant metastasis-free survival (DMFS) in respective subsets of 87 and 106 informative IBC samples. Correlations were investigated with predictive and prognostic gene expression signatures published in nIBC (nIBC-GES). Supervised analyses tested genes and activation signatures of 19 biological pathways and 234 transcription factors. RESULTS: Three of five tested prognostic nIBC-GES and the two tested predictive nIBC-GES discriminated between IBC with and without pCR, as well as two interferon activation signatures. We identified a 107-gene signature enriched for immunity-related genes that distinguished between responders and nonresponders in IBC. Its robustness was demonstrated by external validation in three independent sets including two IBC sets and one nIBC set, with independent significant predictive value in IBC and nIBC validation sets in multivariate analysis. We found no robust signature associated with DMFS in patients with IBC, and neither of the tested prognostic GES, nor the molecular subtypes were informative, whereas they were in our nIBC series (220 stage I-III informative samples). CONCLUSION: Despite the relatively small sample size, we show that response to neoadjuvant CT in IBC is, as in nIBC, associated with immunity-related processes, suggesting that similar mechanisms responsible for pCR exist. Analysis of a larger IBC series is warranted regarding the correlation of gene expression profiles and DMFS.
Subject(s)
Carcinoma, Ductal, Breast/metabolism , Inflammatory Breast Neoplasms/metabolism , Transcriptome , Adult , Aged , Aged, 80 and over , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/secondary , Chemotherapy, Adjuvant , Disease-Free Survival , Estrogen Receptor alpha/genetics , Estrogen Receptor alpha/metabolism , Female , Gene Expression Profiling , Humans , Inflammatory Breast Neoplasms/drug therapy , Inflammatory Breast Neoplasms/mortality , Inflammatory Breast Neoplasms/pathology , Kaplan-Meier Estimate , Middle Aged , Neoadjuvant Therapy , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolismABSTRACT
Background The genomic grade index (GGI) completes the prognostic value of histological grade (HG). Other proliferation markers include the mitotic activity index (MAI) and the Ki67 immunohistochemistry (IHC) status. We compared the prognostic value of GGI, HG, MAI, Ki67 IHC and messenger RNA (mRNA) status in node-positive breast cancer (BC) patients treated with adjuvant anthracycline-based chemotherapy in the prospective PACS01 trial. Patients and methods The five proliferation-related parameters (GGI, Ki67 mRNA expression and centrally determined HG, MAI, and Ki67 IHC status) of tumours were available for 204 cases and analysed as continuous values. We compared the correlations of each one with the other proliferation-related parameters and with histoclinical variables including the disease-free survival (DFS). Results Expected correlations were observed between the five parameters and for each parameter with biological features (hormone-receptor and HER2 status, molecular subtypes), but the GGI displayed the strongest correlations. The GGI outperformed the prognostic performance of the four other proliferation-related parameters for the DFS in all 204 patients and in the 95 HG2 patients. In multivariate analysis including the classical prognostic factors, only GGI remained significant. Finally, the GGI outperformed the prognostic performance of MKI67 mRNA expression in a series of 1599 samples and 656 HG2 cases. Conclusions In this small pilot biomarker study ancillary to the PACS01 trial, the GGI outperforms the prognostic performance of centrally determined HG, MAI, Ki67 IHC status and mRNA expression. Further validation is warranted in larger series.
Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Ki-67 Antigen/metabolism , Mitotic Index , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/mortality , Clinical Trials, Phase III as Topic , Disease-Free Survival , Female , Humans , Immunohistochemistry , Lymphatic Metastasis , Middle Aged , Multivariate Analysis , Neoplasm Grading , Prognosis , Proportional Hazards Models , ROC Curve , Retrospective StudiesABSTRACT
Background Circulating tumor cells (CTCs) can provide the basis for a liquid biopsy and may guide the use of targeted therapies. We report on unbiased quantification of Her-2 protein expression of CTCs. Patients and methods Her-2 assessment of CTCs was carried out using the CellSearch(®) system in 103 metastatic (M1) and 88 non-metastatic (M0) breast-cancer patients. Expression of Her-2 on CTCs was determined by a manual review and an automated algorithm using Her-2- fluorescein isothiocyanate (FITC) fluorescence of leukocytes to determine the Her-2-expression threshold in each sample. Results Her-2 expression of CTCs varied greatly within and among patients compared with Her-2 expression of leukocytes. In M1 patients, a threshold of 75% of Her-2 positive CTCs in patients with ≥5 CTCs was set. Applying this threshold, 9% of M1 patients with Her-2-negative primary tumors had Her-2-positive CTC status and 29% of M1 patients with Her-2-positive primary tumors had Her-2-negative CTC status. No Her-2 discrepancy was observed between CTCs and primary tumors in M0 patients. Conclusions Our findings demonstrate that Her-2 expression is heterogeneous among CTCs within each patient. We show the feasibility of unbiased quantitative and reproducible assessment of treatment targets on CTCs, opening a path towards personalized treatment.
Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Neoplastic Cells, Circulating/metabolism , Receptor, ErbB-2/metabolism , Biomarkers, Tumor/metabolism , Female , Humans , Leukocytes/metabolism , Neoplasm MetastasisABSTRACT
Cancer patients commonly develop anaemia. Erythropoiesis-stimulating agents (ESAs) are frequently used in cancer treatment. Numerous controlled studies indicate that ESAs can raise haemoglobin levels, reduce transfusion requirements and improve quality of life in anaemic cancer patients receiving chemotherapy. They were previously used to enhance response to radiation therapy, via increasing tumour cell oxygenation. Since the 2002 guideline, there has been increasing attention to the safety of ESA treatment in patients with cancer. Two placebo-controlled phase III randomised clinical trials published in 2003 showed evidence of harmful effects of ESAs on survival and/or tumour outcomes. Subsequently, recent trials and several large meta-analyses have confirmed negative impact on survival and/or disease progression. To comprehensively examine whether ESA use affects safety outcomes in cancer patients in different settings (chemotherapy, radiotherapy and targeted therapies), we conducted a literature review of all clinical trials, small and large meta-analyses from 1990 to 2012.
Subject(s)
Anemia/etiology , Hematinics/adverse effects , Neoplasms/drug therapy , Neoplasms/mortality , Blood Transfusion , Disease Progression , Hematinics/therapeutic use , Humans , Neoplasms/complications , Prognosis , Survival RateABSTRACT
Physical activity has been shown to have many benefits, including reducing cancer-related fatigue (CRF) and improving psychological and physical recovery from breast cancer. Some authors have shown the benefits of aquatic practice, while others have detailed the benefits of group and supervised practice. We hypothesize that an innovative sports coaching proposal could allow a significant adherence of patients and contribute to their health improvement. The main objective is to study the feasibility of an adapted water polo programme (aqua polo) for women after breast cancer. Secondarily we will analyse the effect of such a practice on patients' recovery and study the relationship between coaches and participants. The use of mixed methods will allow us to question the underlying processes precisely. This is a prospective, non-randomized, monocentric study with a sample of 24 breast cancer patients after treatment. The intervention is a 20 week programme (1 session per week) of aqua polo in a swim club facility, supervised by professional water-polo coaches. The variables measured are patient participation, quality of life (QLQ BR23), CRF (R-PFS) and post-traumatic growth (PTG-I) as well as different variables to observe physical capacity (strength with dynamometer, step-test and arm amplitude). The quality of the coach-patient relationship will be evaluated (CART-Q) to explore its dynamics. Participatory observations and interviews will be carried out to report on the interactions between the coach and the participants during the sessions. Registration number and name of trial registry: No. EudraCT or ID-RCB: 2019-A03003-54 and NCT: NCT04235946.
ABSTRACT
BACKGROUND: Sunitinib is a standard of care for metastatic renal cell carcinoma (mRCC). Hypothyroidism is frequently observed under sunitinib therapy. This study was conducted to prospectively determine the correlation between thyroid function and progression-free survival (PFS) in this population. PATIENTS AND METHODS: One hundred and eleven mRCC patients treated with sunitinib were evaluated for serum thyroid-stimulating hormone (TSH) and T4 levels before treatment and every 6 weeks during treatment. Survival was analysed according to a landmark method with a cut-off of 6 months, excluding early progressive or early-censored patients. RESULTS: Out of the 102 patients with normal baseline thyroid function, 53% developed thyroid dysfunction, including 95% hypothyroidisms out of which 90.9% received L-thyroxine replacement. Median time to TSH alteration was 5.4 months. Median PFS was 11.7 months for the entire population. Median PFS was not different between the groups with abnormal or normal thyroid function after 6 months of treatment (18.9 and 15.9 months, respectively, log-rank P = 0.94, hazard ratio = 1.02, 95% confidence interval = 0.54-1.93). There was no difference even after adjustment for Memorial Sloan-Kettering Cancer Centre classification and therapy line. CONCLUSIONS: Abnormal thyroid function with hormonal substitution did not increase survival in our population, independent of initial prognosis and previous treatments. Larger comparative studies are deserved to validate these conclusions.
Subject(s)
Carcinoma, Renal Cell/mortality , Hypothyroidism/chemically induced , Hypothyroidism/epidemiology , Kidney Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Carcinoma, Renal Cell/drug therapy , Disease-Free Survival , Female , Humans , Incidence , Indoles/adverse effects , Kaplan-Meier Estimate , Kidney Neoplasms/drug therapy , Male , Middle Aged , Proportional Hazards Models , Pyrroles/adverse effects , Sunitinib , Treatment OutcomeABSTRACT
BACKGROUND: Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. PATIENTS AND METHODS: The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m(2) i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. RESULTS: Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). CONCLUSION: The addition of sorafenib to gemcitabine does not improve PFS in APC patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Niacinamide/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Phenylurea Compounds/therapeutic use , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Disease-Free Survival , Double-Blind Method , Female , Humans , Male , Middle Aged , Niacinamide/administration & dosage , Niacinamide/adverse effects , Niacinamide/therapeutic use , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/adverse effects , Placebos , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Ribonucleotide Reductases/antagonists & inhibitors , Sorafenib , GemcitabineABSTRACT
The aim of this study was to document how breast cancer patients perceive their prognosis and a tailored treatment based on tumour gene expression analysis, and to identify the features of this approach that may impact its clinical application. In-depth interviews were conducted at three French cancer centres with 37 women (35-69 years of age) with node-positive breast cancer undergoing an adjuvant chemotherapy regimen defined on the basis of the genomic signature predicting the outcome after chemotherapy. Several concerns were identified. First, some misconceptions about these methods were identified due to semantic confusions between the terms 'genomic' and 'genetic', which generated anxiety and uncertainty about the future. Second, the 'not done' and 'not interpretable' signatures were misinterpreted by the women and associated with highly negative connotations. However, the use of tumour genomic analysis to adapt the treatment to each patient received most of the patients' approval because it was perceived as an approach facilitating personalised medicine. In conclusion, improving the quality of provider/patient communications should enable patients to play a more active part in the decision making about their treatment. This will ensure that those who agree to have tumour gene analysis have realistic expectations and sound deductions about the final result disclosure process.
Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/psychology , Gene Expression Profiling , Health Knowledge, Attitudes, Practice , Adult , Aged , Attitude to Health , Breast Neoplasms/genetics , Chemotherapy, Adjuvant , Female , France , Humans , Middle Aged , Qualitative ResearchABSTRACT
BACKGROUND: Prognosis of ovarian carcinoma is poor, heterogeneous, and not accurately predicted by histoclinical features. We analysed gene expression profiles of ovarian carcinomas to identify a multigene expression model associated with survival after platinum-based therapy. METHODS: Data from 401 ovarian carcinoma samples were analysed. The learning set included 35 cases profiled using whole-genome DNA chips. The validation set included 366 cases from five independent public data sets. RESULTS: Whole-genome unsupervised analysis could not distinguish poor from good prognosis samples. By supervised analysis, we built a seven-gene optimal prognostic model (OPM) out of 94 genes identified as associated with progression-free survival. Using the OPM, we could classify patients in two groups with different overall survival (OS) not only in the learning set, but also in the validation set. Five-year OS was 57 and 27% for the predicted 'Favourable' and 'Unfavourable' classes, respectively. In multivariate analysis, the OPM outperformed the individual current prognostic factors, both in the learning and the validation sets, and added independent prognostic information. CONCLUSION: We defined a seven-gene model associated with outcome in 401 ovarian carcinomas. Prospective studies are warranted to confirm its prognostic value, and explore its potential ability for better tailoring systemic therapies in advanced-stage tumours.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/genetics , Carcinoma/diagnosis , Carcinoma/drug therapy , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/drug therapy , Platinum Compounds/therapeutic use , Adult , Aged , Aged, 80 and over , Biomarkers, Pharmacological/analysis , Biomarkers, Tumor/analysis , Carcinoma/genetics , Carcinoma/mortality , Decision Support Techniques , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Genes, Neoplasm/physiology , Humans , Microarray Analysis , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Platinum Compounds/administration & dosage , Prognosis , Treatment OutcomeABSTRACT
BACKGROUND: Inflammatory breast cancer (IBC) represents the most aggressive presentation of breast cancer. Women diagnosed with IBC typically have a poorer prognosis compared with those diagnosed with non-IBC tumors. Recommendations and guidelines published to date on the diagnosis, management, and follow-up of women with breast cancer have focused primarily on non-IBC tumors. Establishing a minimum standard for clinical diagnosis and treatment of IBC is needed. METHODS: Recognizing IBC to be a distinct entity, a group of international experts met in December 2008 at the First International Conference on Inflammatory Breast Cancer to develop guidelines for the management of IBC. RESULTS: The panel of leading IBC experts formed a consensus on the minimum requirements to accurately diagnose IBC, supported by pathological confirmation. In addition, the panel emphasized a multimodality approach of systemic chemotherapy, surgery, and radiation therapy. CONCLUSIONS: The goal of these guidelines, based on an expert consensus after careful review of published data, is to help the clinical diagnosis of this rare disease and to standardize management of IBC among treating physicians in both the academic and community settings.
Subject(s)
Biomarkers, Tumor/metabolism , Inflammatory Breast Neoplasms/diagnosis , Inflammatory Breast Neoplasms/therapy , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Aromatase Inhibitors/therapeutic use , Diagnostic Techniques and Procedures , Female , Humans , Neoadjuvant Therapy , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasm Staging , Radiotherapy, Adjuvant , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Tamoxifen/therapeutic use , TrastuzumabABSTRACT
BACKGROUND: The impact of the first coronavirus disease 2019 (COVID-19) wave on cancer patient management was measured within the nationwide network of the Unicancer comprehensive cancer centers in France. PATIENTS AND METHODS: The number of patients diagnosed and treated within 17 of the 18 Unicancer centers was collected in 2020 and compared with that during the same periods between 2016 and 2019. Unicancer centers treat close to 20% of cancer patients in France yearly. The reduction in the number of patients attending the Unicancer centers was analyzed per regions and cancer types. The impact of delayed care on cancer-related deaths was calculated based on different hypotheses. RESULTS: A 6.8% decrease in patients managed within Unicancer in the first 7 months of 2020 versus 2019 was observed. This reduction reached 21% during April and May, and was not compensated in June and July, nor later until November 2020. This reduction was observed only for newly diagnosed patients, while the clinical activity for previously diagnosed patients increased by 4% similar to previous years. The reduction was more pronounced in women, in breast and prostate cancers, and for patients without metastasis. Using an estimated hazard ratio of 1.06 per month of delay in diagnosis and treatment of new patients, we calculated that the delays observed in the 5-month period from March to July 2020 may result in an excess mortality due to cancer of 1000-6000 patients in coming years. CONCLUSIONS: In this study, the delays in cancer patient management were observed only for newly diagnosed patients, more frequently in women, for breast cancer, prostate cancer, and nonmetastatic cancers. These delays may result is an excess risk of cancer-related deaths in the coming years.
Subject(s)
COVID-19 , Neoplasms/complications , COVID-19/complications , Female , France , Humans , Male , SARS-CoV-2ABSTRACT
BACKGROUND: Participants are showing great interest these days in obtaining the results of clinical trials. The aim of this study was to assess patients' uptake and understanding of the results of the trial in which they have participated and the impact of a letter offering patients the possibility of consulting the trial results on a specific website. METHODS: Breast cancer patients participating in a trial on the efficacy of Trastuzumab were randomly subdivided into an Internet group (who received the letter of invitation) and a control group (who did not receive it). Among 115 HER2-positive women from 21 centres, 107 (93%) answered a self-administered questionnaire. RESULTS: Most of the patients in both groups had access to the Internet (72.0%). The majority (97.2%) stated that receiving information about the trial results would be useful, and the oncologist was the most frequently preferred information provider. The Internet group's declared uptake of the trial results was only slightly higher (47.1% vs 33.9%; P=0.166); however, they understood the results significantly more accurately (18.8% vs 5.6%; P=0.039). INTERPRETATION: Although Internet was not the respondents' preferred source of information, the possibility of using this source slightly increased the uptake and understanding of the results.
Subject(s)
Comprehension , Information Dissemination/methods , Randomized Controlled Trials as Topic , Aged , Breast Neoplasms/drug therapy , Correspondence as Topic , Female , Humans , Internet , Middle Aged , Patient Education as Topic , Patient Participation , Patient PreferenceABSTRACT
BACKGROUND: Using data from the PACS 01 randomized trial, we evaluated the cost-effectiveness of anthracyclines plus docetaxel (Taxotere; FEC-D) versus anthracyclines alone (FEC100) in patients with node-positive breast cancer. PATIENTS AND METHODS: Costs and outcomes were assessed in 1996 patients and the incremental cost-effectiveness ratios (ICERs) were estimated, using quality-adjusted life years (QALYs) as outcome. To deal with uncertainty due to sampling fluctuations, confidence regions around the ICERs were calculated and cost-effectiveness acceptability curves were drawn up. Sensitivity analyses were also carried out to assess the robustness of conclusions. RESULTS: The mean cost of treatment was 33% higher with strategy FEC-D, but this difference decreased to 18% at a 5-year horizon. The ICER of FEC-D versus FEC100 was estimated to be 9665euro per QALY gained (95% confidence interval euro2372-euro55 515). The estimated probability that FEC-D was cost-effective reached >96% for a threshold of euro50 000 per QALY gained. If the price of taxane decreased slightly, the ICER would reach some very reasonable levels and this strategy would therefore be much more cost-effective. CONCLUSION: The sequential use of FEC100 followed by docetaxel appears to be a cost-effective alternative, even when uncertainty is taken into account.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/economics , Lymph Nodes/pathology , Adult , Aged , Anthracyclines/administration & dosage , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Cost-Benefit Analysis , Docetaxel , Female , Humans , Middle Aged , Models, Economic , Neoplasm Metastasis , Neoplasm Staging , Quality-Adjusted Life Years , Survival Rate , Taxoids/administration & dosage , Treatment OutcomeABSTRACT
Removal of residual masses after chemotherapy in non-seminomatous germ cell tumours (NSGCTs) remains the standard of care. We evaluated in a retrospective and monocentric study potential prognostic factors. Fifty-one patients underwent surgery after chemotherapy for NSGCT. We estimated event-free survival with Kaplan-Meier method and used Cox proportional hazards regression analysis to assess the prognostic significance of risk factors. Histology of residual masses revealed fibrosis in 25 (49%), mature teratoma in 18 (35%) and viable germ cells in 8 (16%). Alpha-fetoprotein mean level at diagnosis was higher in patients with residual masses showing mature teratoma and/or viable malignant cells (P = 0.036). In multivariate analysis, poor prognosis group according to International Germ Cell Cancer Collaborative Group was associated with worse outcome compared with good and intermediate prognosis groups (hazard ratio for events = 26.4; 95% confidence interval 2.46-283.9; P = 0.006) and primary testicular NSGCT was associated with better event-free survival than extragonadal NSGCTs (hazard ratio for events = 0.04; 95% confidence interval 0.004-0.48; P = 0.01). Resection of residual masses after chemotherapy in NSGCT results in favourable long-term survival in most patients. Our results compared favourably with those reported from higher volume centres.
Subject(s)
Neoplasms, Germ Cell and Embryonal/surgery , Testicular Neoplasms/surgery , Adolescent , Adult , Antineoplastic Agents/therapeutic use , Disease-Free Survival , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm, Residual , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/pathology , Outcome Assessment, Health Care , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Young AdultABSTRACT
Breast cancers that overexpress the ERBB2 tyrosine kinase receptor may be treated with the recombinant humanized monoclonal anti-ERBB2 antibody trastuzumab (herceptin). However, resistance to this targeted therapy is frequent. We have determined the response of 18 breast tumor cell lines to trastuzumab and compared it with the ERBB2 phosphorylation status using antibodies directed against tyrosine residue 1248. We show that sensitivity to trastuzumab is frequently associated with the expression of a phosphorylated ERBB2 protein.