Impact de l obésité et de la composition corporelle sur la toxicité du Docetaxel (étude rétrospective sur 200 patientes traitées entre 2008 et 2010 au centre Henri Becquerel pour un cancer du sein localisé)

La prévalence de l obésité augmente depuis ces vingt dernières années et l obésité est un facteur de risque connu de cancer du sein chez les femmes ménopausées. Malgré le nombre important de femmes obèses traitées par Docetaxel pour un cancer du sein, il existe très peu de données concernant sa tolérance et les facteurs prédictifs de sa toxicité dans cette sous population. La composition corporelle a été montrée comme étant un facteur prédictif de la toxicité d autres chimiothérapies. Objectifs : Evaluer la tolérance du Docetaxel chez les patientes obèses et la valeur prédictive de la composition corporelle sur la tolérance du Docetaxel.Matériels et méthodes : Il s agit d une étude monocentrique rétrospective de patientes traitées pour un cancer du sein localisé et ayant reçu une chimiothérapie séquentielle par FEC 100 puis Docetaxel en traitement adjuvant ou néoadjuvant. Toutes les patientes obèses (IMC >= 30 kg/m ) traitées entre 2008 et 2010 ont été incluses (n=100) et le même nombre de patientes non obèses (n=100) traitées sur cette même période ont été tirées au sort. Nous avons collecté les toxicités objectives (hématologiques, cardiaques, hospitalisations) et les données relatives à la dose intensité (diminutions de doses, reports de cures, modifications de la chimiothérapie, arrêts de la chimiothérapie), afin de calculer le ratio (Doses totales reçues/Doses totales prévues) pour chaque drogue. Nous avons évalué la composition corporelle sur 89 patientes ayant bénéficié d un scanner lors du bilan initial. Résultats : Parmi les 469 patientes traitées, durant ces 3 ans, par une chimiothérapie séquentielle FEC 100/Docetaxel pour un cancer du sein localisé, 100 patientes sont obèses, soit 21% de la population traitée. Les 100 patientes obèses et les 100 patientes non obèses tirées au sort possèdent les mêmes caractéristiques cliniques et histologiques, sauf pour les cancers inflammatoires (stade T4d) qui concernent 10 % des patientes obèses et 1% des patientes non obèses (p=0,02). Le ratio de Docetaxel est plus fréquemment inférieur à 1 chez les patientes obèses (18%) que chez les patientes non obèses (6%) (p=0,02). Les toxicités cutanéo-muqueuses sont La principale cause de diminution du ratio de Docetaxel. Par contre, il n y a pas de différence concernant le ratio d Epirubicine entre les patientes obèses et non obèses. Lorsqu on considère les 200 patientes de l étude, on retrouve 4 facteurs prédictifs d un ratio de Docetaxel inférieur à 1 : un âge plus élevé (p=0,01), un IMC plus élevé (p=0,005), une surface corporelle plus élevée (p=0,05) et un poids plus élevé (p=0,02). En analyse multivariée, on ne retrouve que l âge et l IMC comme facteurs prédictifs (p=0,02). Lorsqu on considère les 89 patientes avec un scanner, on retrouve 4 facteurs prédictifs d un ratio de Docetaxel inférieur à 1: une masse grasse plus élevée (p=0,004), un IMC plus élevé (p=0,02), une surface corporelle plus élevée (p=0,03) et un poids plus élevé (p=0,02). En analyse multivariée, on retrouve comme facteurs prédictifs la masse grasse (p=0,003) et l administration de Trastuzumab en concomitant du Docetaxel (p=0,04). Conclusion : Dans cette étude, la dose intensité du Docetaxel est inférieure chez les patientes obèses. La masse grasse évaluée par scanner apparait être un facteur prédictif indépendant de la toxicité du Docetaxel.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

A higher body mass index and fat mass predict the reduction of dose-intensity for docetaxel but not for epirubicin in early breast cancer chemotherapy

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Influence of adjuvant chemotherapy on anti-Müllerian hormone in women below 35 years treated for early breast cancer

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Clinical relevance of circulating ESR1 mutations during endocrine therapy for advanced hormone-dependent endometrial carcinoma

Abstract Objective Endocrine therapy is frequently administered in patients with hormone dependent (HR+) metastatic endometrial cancer. ESR1 mutations have emerged as a key mechanism of aromatase inhibitor (AI) resistance in HR + metastatic breast cancer and can be monitored using circulating tumor DNA (ctDNA). The aim of this study was to explore the incidence and clinical relevance of circulating ESR1 mutations in patients treated by AI or megestrol acetate (M) for advanced endometrial carcinoma. Methodology This single-center retrospective study was performed at the Henri Becquerel Center (Rouen) and looked for circulating ESR1 gene mutations by droplet digital PCR (E380Q, L536R, Y537S, Y537N, Y537C, D538G, S463P) in patients with advanced HR + endometrial carcinoma treated between 2008 and 2020 for at least 30 days by AI or M. Analyses were performed before exposure and at progression/during endocrine therapy. Results Twenty-two patients were included: 13 were treated with AI, 12 of whom progressed; 9 patients were treated with M, 8 of whom progressed. 68.1% of the patients had low-grade endometrial carcinoma and 54.5% had received chemotherapy in the metastatic setting. The median duration of treatment was 152 days (min 47 – max 629) with AI and 155 days (min 91-max 1297) with M. Under AI, there was no ESR1 mutation at baseline, and one Y537C mutation at progression with a variant allele frequency (VAF) of 0.14%. Under M, one patient had a Y537C (VAF 0.2%) at baseline that disappeared during treatment. Another patient had a Y537S mutation emergence at progression after 91 days of treatment (VAF 1.83%). There was no significant difference between the circulating DNA concentration before and after hormone therapy (p = 0.16). Conclusion ESR1 mutations do not seem to be involved in the mechanisms of resistance to AI or M in HR+ endometrial cancer. The clinical relevance of their detection is not demonstrated

Impact of deleterious germline BRCA mutations, addition of taxanes and use of adjuvant endocrine therapy (ET) on anti-müllerian hormone (AMH) levels in early breast cancer (EBC) patients treated by adjuvant chemotherapy (CT)

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Impact of Taxanes, Endocrine Therapy, and Deleterious Germline BRCA Mutations on Anti-müllerian Hormone Levels in Early Breast Cancer Patients Treated With Anthracycline- and Cyclophosphamide-Based Chemotherapy

International audienceBackground: Limited evidence exists on the impact of adding a taxane, using endocrine therapy and carrying a deleterious germline BRCA mutation on ovarian reserve measured by anti-müllerian hormone (AMH) levels of young breast cancer patients receiving (neo)adjuvant cyclophosphamide- and anthracycline-based chemotherapy.Methods: This is a biomarker analysis including young (≤ 40 years) early breast cancer patients with known germline BRCA mutational status and available prospectively collected frozen plasma samples before and after chemotherapy. Chemotherapy consisted of either six cycles of FEC (5 fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) or three cycles of FEC followed by three cycles of docetaxel (D, 100 mg/m2). Endocrine therapy consisted of tamoxifen (±GnRH agonists). AMH levels at baseline, 1 and 3 years after diagnosis were compared according to type of chemotherapy (FEC only vs. FEC-D), use of endocrine therapy (yes vs. no) and deleterious germline BRCA mutations (mutated vs. negative).Results: Out of 148 included patients, 127 (86%) received D following FEC chemotherapy, 90 (61%) underwent endocrine therapy, and 35 (24%) had deleterious germline BRCA mutations. In the whole cohort, AMH levels drastically dropped 1 year after diagnosis (p < 0.0001) with a slight but significant recovery at 3 years (p < 0.0001). One year after diagnosis, patients treated with FEC only had higher median AMH levels than those who received FEC-D (0.22 vs. 0.04 μg/L, p = 0.0006); no difference was observed at 3 years (0.06 and 0.18 μg/L, p = 0.47). Patients under endocrine therapy had significantly higher AMH levels than those who did not receive this treatment 1 year after diagnosis (0.12 vs. 0.02 μg/L; p = 0.008), with no difference at 3 years (0.11 and 0.20 μg/L, p = 0.22). AMH levels were similar between BRCA-mutated and BRCA-negative patients at baseline (1.94 vs. 1.66 μg/L, p = 0.53), 1 year (0.09 vs. 0.06 μg/L, p = 0.39) and 3 years (0.25 vs. 0.16 μg/L; p = 0.43) after diagnosis.Conclusions: In breast cancer patients receiving FEC chemotherapy, adding D appeared to negatively impact on their ovarian reserve in the short-term; no further detrimental effect was observed for endocrine therapy use and presence of a deleterious germline BRCA mutation

Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS)

International audienceAbstract Background Stereotactic Body Radiation Therapy (SBRT) is an innovative modality based on high precision planning and delivery. Cancer with bone metastases and oligometastases are associated with an intermediate or good prognosis. We assume that prolonged survival rates would be achieved if both the primary tumor and metastases are controlled by local treatment. Our purpose is to demonstrate, via a multicenter randomized phase III trial, that local treatment of metastatic sites with curative intent with SBRT associated of systemic standard of care treatment would improve the progression-free survival in patients with solid tumor (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases compared to patients who received systemic standard of care treatment alone. Methods This is an open-labeled randomized superiority multicenter phase III trial. Patients with up to 3 bone-only metastases will be randomized in a 1:1 ratio.between Arm A (Experimental group): Standard care of treatment & SBRT to all bone metastases, and Arm B (Control group): standard care of treatment. For patients receiving SBRT, radiotherapy dose and fractionation depends on the site of the bone metastasis and the proximity to critical normal structures. This study aims to accrue a total of 196 patients within 4 years. The primary endpoint is progression-free survival at 1 year, and secondary endpoints include Bone progression-free survival; Local control; Cancer-specific survival; Overall survival; Toxicity; Quality of life; Pain score analysis, Cost-utility analysis; Cost-effectiveness analysis and Budget impact analysis. Discussion The expected benefit for the patient in the experimental arm is a longer expectancy of life without skeletal recurrence and the discomfort, pain and drastic reduction of mobility and handicap that the lack of local control of bone metastases eventually inflicts. Trials registration ClinicalTrials.gov NCT03143322 Registered on May 8th 2017. Ongoing stud

A Pragmatic Study Evaluating NEPA Versus Aprepitant for Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy

International audienceBackground Neurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5-hydroxytryptamine-3 (5-HT3) RA and dexamethasone (DEX), have demonstrated clear improvements in chemotherapy-induced nausea and vomiting (CINV) prevention over a 5-HT(3)RA plus DEX. However, studies comparing the NK1RAs in the class are lacking. A fixed combination of a highly selective NK(1)RA, netupitant, and the 5-HT(3)RA, palonosetron (NEPA), simultaneously targets two critical antiemetic pathways, thereby offering a simple convenient antiemetic with long-lasting protection from CINV. This study is the first head-to-head NK(1)RA comparative study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). Materials and Methods This was a pragmatic, multicenter, randomized, single-cycle, open-label, prospective study designed to demonstrate noninferiority of single-dose NEPA to a 3-day aprepitant regimen in preventing CINV in chemotherapy-naive patients receiving AC/non-AC MEC in a real-life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0-120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at -10%. Results Noninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, -2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant. Conclusion This pragmatic study in patients with cancer receiving AC and non-AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3-day aprepitant regimen, with indication of a potential efficacy benefit for NEPA. Implications for Practice In the absence of comparative neurokinin 1 (NK1) receptor antagonist (RA) studies, guideline committees and clinicians consider NK(1)RA agents to be interchangeable and equivalent. This is the first head-to-head study comparing one NK(1)RA (oral netupitant/palonosetron [NEPA]) versus another (aprepitant) in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy. Noninferiority of NEPA versus the aprepitant regimen was demonstrated; the overall complete response (no emesis and no rescue use) rate was numerically higher for NEPA (65%) than aprepitant (54%). As a single-dose combination antiemetic, NEPA not only simplifies dosing but may offer a potential efficacy benefit over the current standard-of-care

Different Prognostic Values of Tumour and Nodal Response to Neoadjuvant Chemotherapy Depending on Subtypes of Inflammatory Breast Cancer, a 317 Patient-Study

Inflammatory breast cancer (IBC) is a rare entity with a poor prognosis. We analysed the survival outcomes of patients with nonmetastatic IBC and the prognostic value of tumour or nodal responses to assess their individual prognostic impact across IBC subtypes. This retrospective multicentre study included patients diagnosed with IBC between 2010 and 2017 to account for advances in neoadjuvant systemic therapies and modern radiotherapy at seven oncology centres in France. Three hundred and seventeen patients were included and analysed. After a median follow-up of 52 months, the 5-year DFS was lower for triple-negative (TN) (50.1% vs. 63.6%; p &lt; 0.0001). After multivariate analyses, incomplete nodal response was the only significant prognostic factor in the triple-negative group (HR:6.06). The poor prognosis of TN-IBC was reversed in the case of nodal response after neoadjuvant chemotherapy. Breast response does not appear to be a decisive prognostic factor in patients with TN-IBC compared to lymph node response. Despite improvements in neoadjuvant treatments, IBC remains associated with a poor prognosis. In TN-IBC patients, lack of pathological complete node response was associated with poorer survival than any other group. Treatment intensification strategies are worth investigating

Data_Sheet_1_Post-traumatic stress disorder symptoms and associated factors in breast cancer patients during the first COVID-19 lockdown in France.docx

IntroductionWe aimed to study post-traumatic stress disorder (PTSD) symptoms in breast cancer (BC) patients during the coronavirus disease (COVID-19) pandemic.Materials and methodsWe included BC patients receiving medical treatment during the first COVID-19 lockdown in France. PTSD symptoms were evaluated using the Impact of Event Scale-Revised (IES-R) questionnaire. Quality of life [Functional Assessment of Cancer Therapy-General (FACT-G)], cognitive complaints [Functional Assessment of Cancer Therapy–Cognitive Function (FACT-Cog)], insomnia [Insomnia Severity Index (ISI)], and psychosocial experiences during lockdown were also evaluated. Multivariable logistic regression was used to identify clinical factors (from medical records) and psychosocial factors (from questionnaires) associated with PTSD symptoms.ResultsAmong the 253 included BC patients (mean age: 58), 46% had metastatic cancer and 52% were treated by chemotherapy alone. COVID-19-induced adjustments in medical oncology practices were experienced by 27% of patients (mainly teleconsultations). No case of COVID-19 was reported; 23% of BC patients had PTSD symptoms. Compared to other patients, patients with PTSD symptoms had more fears relative to COVID-19 infection (83 vs. 60%, p = 0.009), had more feeling of isolation (69 vs. 41%, p = 0.003), and had more prescription or increased use of psychotropic drugs (49 vs. 20%, p = 0.001). In the multivariable model adjusted for clinical factors, fears relative to COVID-19 and increased use of psychotropic drugs were independently associated with PTSD symptoms (OR [95% CI] = 3.01 [1.20–8.44] and 3.45 [1.48–8.17], respectively). Besides, patients with PTSD symptoms had poor quality of life (QoL), and more cognitive complaints and insomnia.ConclusionPost-traumatic stress disorder symptoms were observed in 23% of BC patients during the first COVID-19 lockdown in France. Psychological supports are needed for patients treated during the COVID-19 pandemic.</p