Publications by authors named "Pierre-Etienne Heudel"

27 Publications

  • Page 1 of 1

Patterns of Sequelae in Women with a History of Localized Breast Cancer: Results from the French VICAN Survey.

Cancers (Basel) 2021 Mar 8;13(5). Epub 2021 Mar 8.

Department Prevention, Cancer, Environment, Léon Bérard Cancer Center, 69008 Lyon, France.

Breast cancer (BC) remains complex for women both physically and psychologically. The objectives of this study were to (1) assess the evolution of the main sequelae and treatment two and five years after diagnosis in women with early-stage breast cancer, (2) explore patterns of sequelae associated with given sociodemographic, clinical, and lifestyle factors. The current analysis was based on 654 localized BC patients enrolled in the French nationwide longitudinal survey "vie après cancer" VICAN (January-June 2010). Information about study participants was collected at enrollment, two and five years after diagnosis. Changes over time of the main sequelae were analyzed and latent class analysis was performed to identify patterns of sequelae related to BC five years after diagnosis. The mean age (±SD) of study participants at inclusion was 49.7 (±10.5) years old. Six main classes of sequelae were identified two years and five years post-diagnosis (functional, pain, esthetic, fatigue, psychological, and gynecological). A significant decrease was observed for fatigue ( = 0.03) and an increase in cognitive sequelae was reported ( = 0.03). Two latent classes were identified-functional and esthetic patterns. Substantial sequelae remain up to five years after BC diagnosis. Changes in patient care pathways are needed to identify BC patients at a high risk.
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http://dx.doi.org/10.3390/cancers13051161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962808PMC
March 2021

Characteristics and outcome of breast cancer-related microangiopathic haemolytic anaemia: a multicentre study.

Breast Cancer Res 2021 Jan 19;23(1). Epub 2021 Jan 19.

Department of Medical Oncology, Institut Curie, Paris and Saint Cloud, France.

Background: Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA.

Methods: Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records.

Results: Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2-, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0-1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 [1.6; 31.8]), elevated bilirubin (OR = 6.9 [1.1; 42.6]), haemoglobin < 8.0 g/dL (OR = 3.7 [0.9; 16.7]) and prothrombin time < 50% (OR = 9.1 [1.2; 50.0]). A score to predict early death displayed a sensitivity of 86% (95% CI [0.67; 0.96]), a specificity of 73% (95% CI [0.52; 0.88]) and an area under the curve of 0.90 (95% CI [0.83; 0.97]).

Conclusions: Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.
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http://dx.doi.org/10.1186/s13058-021-01386-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814553PMC
January 2021

Impact of body mass index on overall survival in patients with metastatic breast cancer.

Breast 2021 Feb 1;55:16-24. Epub 2020 Dec 1.

Department of Cancer Medicine, Gustave Roussy, 114 Rue Edouard Vaillant, 94800, Villejuif, France; Department of Medical Oncology, CHU de Limoges, 2 Avenue Martin Luther King, Limoges, France.

Background: High Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC).

Methods: The National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers.

Results: Of 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m (range 12.1-66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2-48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02-1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect.

Conclusion: Overweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.
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http://dx.doi.org/10.1016/j.breast.2020.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725947PMC
February 2021

Effect of Weekly Paclitaxel With or Without Bevacizumab on Progression-Free Rate Among Patients With Relapsed Ovarian Sex Cord-Stromal Tumors: The ALIENOR/ENGOT-ov7 Randomized Clinical Trial.

JAMA Oncol 2020 Oct 8. Epub 2020 Oct 8.

GINECO and Centre Léon Bérard, Lyon, France.

Importance: To our knowledge, this is the first randomized trial in sex cord-stromal tumors, and it establishes weekly paclitaxel as standard-of-care therapy after platinum-based therapy in this setting.

Objective: To determine the efficacy of weekly paclitaxel with or without bevacizumab as treatment for relapsed sex cord-stromal tumors and evaluate whether the addition of bevacizumab to weekly paclitaxel improves 6-month progression-free rate.

Design, Setting, And Participants: This open-label, academic, international, randomized phase 2 trial (ALIENOR) was conducted at 28 referral centers in France, Germany, Italy, Japan, and Belgium in collaboration with the Rare Tumor committee of the Gynecologic Cancer InterGroup and used an adaptive bayesian design. It included 60 women with sex cord-stromal tumors that had relapsed after at least 1 platinum-based chemotherapy. Enrollment occurred from 2013 to 2016, and the final analysis database lock was on March 27, 2020 (median follow-up, 38.9 months).

Interventions: Participants were randomized to receive either paclitaxel (80 mg/m2, days 1, 8, and 15 every 4 weeks) alone or paclitaxel with bevacizumab (10 mg/kg, every 2 weeks) for 6 cycles followed by maintenance bevacizumab (15 mg/kg, every 3 weeks) for up to 1 year or until progression or unacceptable toxicity. Crossover to bevacizumab was permitted after progression during or following paclitaxel alone.

Main Outcomes And Measures: Six-month progression-free rate.

Results: Sixty patients (predominantly with granulosa cell tumors) were randomized, 32 to receive single-agent paclitaxel (median [interquartile range] age at inclusion, 60 [53-64] years) and 28 to receive paclitaxel-bevacizumab (median [interquartile range] age at inclusion, 55 [47-61] years; 1 did not receive treatment). The estimated 6-month progression-free rate was 71% (95% credible interval, 55%-84%) with paclitaxel alone and 72% (95% credible interval, 55%-87%) with paclitaxel-bevacizumab. The bayesian estimate for the probability that the 6-month progression-free rate distribution was higher with the combination than with paclitaxel alone was 57%, less than the predefined superiority threshold. The objective response rate increased from 25% (95% CI, 12%-43%) to 44% (95% CI, 26%-65%) with the addition of bevacizumab. One patient discontinued combination therapy within 6 months because of toxicity.

Conclusions And Relevance: Weekly paclitaxel is a new option for relapsed sex cord-stromal tumors. In this international randomized clinical trial of patients with relapsed sex cord-stromal tumors unsuitable for surgery, adding bevacizumab to weekly paclitaxel does not improve clinical benefit.

Trial Registration: ClinicalTrials.gov Identifier: NCT01770301.
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http://dx.doi.org/10.1001/jamaoncol.2020.4574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545353PMC
October 2020

GINECO Prospective Non-interventional PROSPECTYON Study: Trabectedin Plus Pegylated Liposomal Doxorubicin for Platinum-sensitive Recurrent Ovarian Cancer.

Anticancer Res 2020 Jul;40(7):3939-3945

ORACLE-Centre d'Oncologie de Gentilly, Nancy, France.

Background: Trabectedin and pegylated liposomal doxorubicin (PLD) is an effective combination therapy for platinum-sensitive recurrent ovarian cancer (ROC), particularly for disease relapsing within 6-12 months of platinum therapy. The non-interventional PROSPECTYON study evaluated trabectedin/PLD in French clinical practice.

Patients And Methods: Patients with ROC after at least one platinum-based regimen received 1.1 mg/m trabectedin plus 30 mg/m PLD every 3 weeks. Efficacy and safety were evaluated in subgroups according to platinum-free interval [6-12 versus ≥12 months (partially or fully platinum sensitive, respectively)].

Results: Recurrent disease was partially platinum-sensitive in 58 patients and fully sensitive in 33 patients treated between July 2014 and June 2016. Patients in both subgroups received a median of six cycles of trabectedin and PLD. The most common grade 3 or more toxicities were haematological. Median progression-free survival was 6 months for both subgroups.

Conclusion: Trabectedin/PLD is a valuable treatment option for partially or fully platinum-sensitive ROC.
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http://dx.doi.org/10.21873/anticanres.14385DOI Listing
July 2020

Analysis of the StoRM cohort reveals physical activity to be associated with survival in metastatic breast cancer.

Sci Rep 2020 07 1;10(1):10757. Epub 2020 Jul 1.

Oncology Department, Centre Léon Bérard, Lyon, France.

Benefits of physical activity are widely demonstrated for early stage cancers but few studies have focused on metastatic disease. The purpose of this study was to determine the impact of physical activity on survival in patients with metastatic breast cancer. We conducted a secondary analysis of the national, multicentric, non-randomized, prospective cohort SNPs to Risk of Metastasis (StoRM) study. The level of physical activity was self-reported at inclusion and divided into three categories of physical activity: light level, moderate level, and vigorous level. Overall, 833 patients (56.2%) completed the physical activity questionnaire at baseline on average physical activity during the previous year: 11.6% had a light level of physical activity, 69.0% achieved moderate levels of physical activity and 19.3% reported vigorous levels of physical activity. After adjustment for confounding, physical activity was not statistically significantly associated with overall survival in the whole population. Subgroup analysis identified that both vigorous and moderate physical activity were associated with statistically significantly improved overall survival compared to light physical activity level only in the HER2 positive subgroup (HR 0.23; 95% CI 0.07-0.70, p = 0.01 and HR 0.38; 95% CI 0.15-0.96, p = 0.04). Physical activity done during the previous year was associated with survival in HER2 positive metastatic breast cancer patients. These results suggest that overall survival in metastatic breast cancer patients could be improved through physical activity which should be considered as a complementary intervention for these individuals. The study showed that moderate/vigorous levels of physical activity were associated with better overall survival, and that these associations remained statistically significant in multivariate analysis in the HER2 positive subgroup. These results have clinical relevance and justify the recommendations for physical activity interventions in metastatic breast cancer.
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http://dx.doi.org/10.1038/s41598-020-67431-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329808PMC
July 2020

Feasibility and Health Benefits of an Individualized Physical Activity Intervention in Women With Metastatic Breast Cancer: Intervention Study.

JMIR Mhealth Uhealth 2020 01 28;8(1):e12306. Epub 2020 Jan 28.

Department of Cancer and Environment, Léon Bérard Cancer Center, Lyon, France.

Background: There is limited knowledge regarding the potential benefits of physical activity in patients with metastatic breast cancer.

Objective: The Advanced stage Breast cancer and Lifestyle Exercise (ABLE) Trial aimed to assess the feasibility of a physical activity intervention in women with metastatic breast cancer and to explore the effects of physical activity on functional, psychological, and clinical parameters.

Methods: The ABLE Trial was a single-arm, 6-month intervention study with a home-based, unsupervised, and personalized walking program using an activity tracker. At baseline and 6 months, we assessed anthropometrics, functional fitness, physical activity level, sedentary behavior, quality of life, fatigue, and tumor progression. Paired proportions were compared using the McNemar test and changes of parameters during the intervention were analyzed using the Wilcoxon signed-rank test, the Mann-Whitney test, and Spearman rank correlations.

Results: Overall, 49 participants (mean age 55 years; recruitment rate 94%) were enrolled and 96% adhered to the exercise prescription (attrition rate 2%). Statistically significant improvements in the 6-minute walking distance test (+7%, P<.001) and isometric quadriceps strength (+22%, P<.001), as well as decreases in body mass index (-2.5%, P=.03) and hip circumference (-4.0%, P<.001) were observed at 6 months. Quality of life remained stable and a nonstatistically significant decrease (-16%, P=.07) in fatigue was observed.

Conclusions: The high recruitment and adherence rates suggest the willingness of patients with metastatic breast cancer to participate in a physical activity program. The beneficial outcomes regarding physical fitness and anthropometry of this unsupervised physical activity program may encourage these patients to maintain a physically active lifestyle. Future randomized controlled trials with larger sample sizes are warranted.

Trial Registration: ClinicalTrials.gov NCT03148886; https://clinicaltrials.gov/ct2/show/NCT03148886.
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http://dx.doi.org/10.2196/12306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013652PMC
January 2020

Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers.

Gynecol Oncol 2019 11 8;155(2):262-269. Epub 2019 Oct 8.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France; University Claude Bernard (UCBL Lyon1), Lyon, France.

Objective: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice.

Methods: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy.

Results: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) ≥ 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI ≥ 12 months, CR and normalization of CA-125.

Conclusions: Platinum-free interval ≥ 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy.
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http://dx.doi.org/10.1016/j.ygyno.2019.09.008DOI Listing
November 2019

Physical activity preferences before and after participation in a 6-month physical activity intervention among women with metastatic breast cancer.

Eur J Cancer Care (Engl) 2020 Jan 30;29(1):e13169. Epub 2019 Sep 30.

Department of Cancer and Environment, Leon Berard Cancer Center, Lyon, France.

Objective: This secondary analysis of the ABLE Trial (ClinicalTrials.gov NCT03148886) aimed to assess physical activity preferences before and after a 6-month physical activity intervention for women recently diagnosed with metastatic breast cancer and to investigate demographic and clinical correlates of these preferences.

Methods: Forty-nine patients participated in the ABLE Trial, a single-arm, unsupervised 6-month physical activity intervention with activity trackers. At baseline and 6 months, physical activity preferences, physical activity level, clinical variables, demographics and social vulnerability were assessed.

Results: At baseline, 49 participants were included, among whom 85% were interested in receiving physical activity counselling and 89% were interested in following a physical activity programme designed for metastatic breast cancer. At the end of the study, more participants preferred practising in a community fitness centre (66%) rather than at home (19% vs. 44% at baseline, p = .03). A higher social vulnerability score and not being treated by chemotherapy at baseline were significantly associated with lower desire to receive physical activity counselling (p = .01 and p = .04 respectively).

Conclusions: This study will help design future studies within patients with metastatic breast cancer in accordance with their preferences. Designing tailored physical activity interventions according to the participant's preferences may be one key to success for adherence.
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http://dx.doi.org/10.1111/ecc.13169DOI Listing
January 2020

Real-life activity of eribulin mesylate among metastatic breast cancer patients in the multicenter national observational ESME program.

Int J Cancer 2019 12 20;145(12):3359-3369. Epub 2019 Jun 20.

Centre Oscar Lambret, Lille, France.

Eribulin mesylate (EM) was recently approved for metastatic breast cancer (MBC) chemotherapy (CT) in late lines by the FDA, with debated results in second line. We evaluated outcomes in breast cancer patients receiving EM as second, third and fourth line in a national real-life cohort of 16,703 consecutive MBC patients initiating their first metastatic therapeutic line between 2008 and 2014. Primary and secondary objectives were overall survival (OS) and progression-free survival (PFS). An imbalance was seen for HER2+ tumors and concomitant anti-HER2 targeted therapies use, we thus performed a subanalysis in HER2- patients. PFS and OS were significantly better in EM patients in third and fourth lines, compared to "Other chemotherapies" patients (PFS: 4.14 vs. 3.02 months, p = 0.0010; 3.61 vs. 2.53 months, p = 0.0102, third and fourth-line; OS: 11.27 vs. 7.65 months, p = 0.0001; 10.91 vs. 5.95 months, p < 0.0001, third and fourth-line). No significant difference was reported in second-line (PFS: 5.06 vs. 4.14 months, p = 0.1171; OS: 13.99 vs. 11.66 months, p = 0.151). Among HER2- patients, a significant difference was seen for all lines, including 2nd-line (PFS: 4.57 vs. 3.91 months, p = 0.0379; OS: 14.98 vs. 10.51 months, p = 0.0113). In this large real-world database, HER2-negative MBC patients receiving EM in second or later CT line presented significantly better PFS and OS. This difference disappeared in second line in the overall population, probably because of the imbalance in HER2-targeted treatments use. Our results mirror those of the published randomized trials. The effect of anti-HER2 therapies addition in this setting still needs to be defined.
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http://dx.doi.org/10.1002/ijc.32402DOI Listing
December 2019

Feasibility of an exercise and nutritional intervention for weight management during adjuvant treatment for localized breast cancer: the PASAPAS randomized controlled trial.

Support Care Cancer 2019 Sep 24;27(9):3449-3461. Epub 2019 Jan 24.

Léon Bérard Cancer Center, Lyon, France.

Purpose: Lack of physical activity (PA), weight gain, and overweight have been associated with increased risk of recurrence and mortality after breast cancer diagnosis. We evaluated the feasibility of implementing an individualized exercise program and nutritional counseling during adjuvant treatment of localized invasive breast cancer.

Methods: Sixty-one patients eligible for adjuvant chemotherapy were randomized 2:1 to receive a 6-month program of weekly aerobic exercises associated with nutritional counseling (n = 41) or usual care with nutritional counseling (n = 20, one withdrawal). The primary endpoints were the proportion of patients compliant with two weekly supervised sessions and their overall adherence (i.e., proportion of supervised and unsupervised sessions completed versus planned sessions).

Results: Ten percent of patients in the intervention group were compliant with the two weekly supervised sessions for 6 months, but the overall median adherence rate was 85% of supervised and non-supervised sessions completed. Non-adherence was mainly due to intrinsic reasons (medical, organizational, psychological barriers). Adherence was positively associated with education and baseline PA level and inversely associated with baseline weight and tumor grade. No statistically significant benefits were observed in the intervention group, even if overall PA level and body composition improved and anthropometrics were maintained over time (p < 0.05).

Conclusions: Overall, there was good adherence with the 6-month exercise program during adjuvant treatment for breast cancer, despite poor compliance to twice-weekly supervised sessions. This study highlights the need for flexible exercise modalities and innovative experimental design to reach patients who would most adhere and benefit from intervention.

Trial Registration: ClinicalTrials.gov Identifier: NCT01331772. Registered 8 April 2011, https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1.
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http://dx.doi.org/10.1007/s00520-019-4658-yDOI Listing
September 2019

Does a homeopathic medicine reduce hot flushes induced by adjuvant endocrine therapy in localized breast cancer patients? A multicenter randomized placebo-controlled phase III trial.

Support Care Cancer 2019 May 7;27(5):1879-1889. Epub 2018 Sep 7.

Department of Medical Oncology, Centre Léon Bérard, 28 rue Laennec, 69373, Lyon Cedex 08, France.

Purpose: Endocrine therapy (ET) used to reduce the risk of recurrence in hormone receptor-expressing disease (75% of breast cancers) is associated with worsening of climacteric symptoms with a negative impact on quality of life (QoL). Homeopathy might allow a better management of hot flushes (HF).

Methods: In this multicenter randomized double-blind placebo-controlled phase III study ( ClinicalTrials.gov NCT01246427), we enrolled ≥ 18 years old women with histologically proven non metastatic localized breast cancer, with Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) ≤ 1, treated for at least 1 month with adjuvant ET, and complaining about moderate to severe HF. Patients should not be scheduled for chemotherapy or radiotherapy, and had no associated pathology known to induce HF. After a 2- to 4-week placebo administration, we randomly assigned (1:1) patients with HFS ≥ 10 using an interactive web-based centralized platform to BRN-01 homeopathic medicine complex (Actheane®) in arm A or Placebo (Arm P). Randomization was stratified by adjuvant ET (taxoxifen/aromatase inhibitor) and recruiting site. HF scores (HFS) were calculated as the mean of HF frequencies before randomization, at 4, and at 8 weeks post-randomization (pre-, 4w,- and 8w-) weighted by a 4-level intensity scale. Primary endpoint was assessed at 4-week post-randomization, as the variation between pre- and 4w-HFS. Secondary endpoints included HFS variation between pre- and 8w-HFS, compliance and tolerance assessed 8 weeks after randomization, and QoL and satisfaction assessed at 4- and 8-week post-randomization.

Results: Two hundred ninety-nine patients were included, and 138 (46.2%) randomized (A, 65; P, 73). Median 4w-HFS absolute variation (A, - 2.9; P, - 2.5 points, p = 0.756) and relative decrease (A, - 17%; P, - 15%, p = 0.629) were not statistically different. However, 4w-HFS decreased for 46 (75%) in A vs 48 (68%) patients in P arm. 4w-QoL was stable or improved for respectively 43 (72%) vs 51 (74%) patients (p = 0.470).

Conclusions: The efficacy endpoint was not reached, and BRN-01 administration was not demonstrated as an efficient treatment to alleviate HF symptoms due to adjuvant ET in breast cancer patients. However, the study drug administration led to decreased HFS with a positive impact on QoL. Without any recommended treatment to treat or alleviate the HF-related disabling symptoms, Actheane® could be a promising option, providing an interesting support for better adherence to ET, thereby reducing the risk of recurrence with a good tolerance profile.
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http://dx.doi.org/10.1007/s00520-018-4449-xDOI Listing
May 2019

A Personalized Physical Activity Program With Activity Trackers and a Mobile Phone App for Patients With Metastatic Breast Cancer: Protocol for a Single-Arm Feasibility Trial.

JMIR Res Protoc 2018 Aug 30;7(8):e10487. Epub 2018 Aug 30.

Inter-University Laboratory of Human Movement Biology, University Claude Bernard Lyon 1, University of Lyon, Lyon, France.

Background: About 5% of breast cancer cases are metastatic at diagnosis, and 20%-30% of localized breast cancer cases become secondarily metastatic. Patients frequently report many detrimental symptoms related to metastasis and treatments. The physical, biological, psychological, and clinical benefits of physical activity during treatment in patients with localized breast cancer have been demonstrated; however, limited literature exists regarding physical activity and physical activity behavior change in patients with metastatic breast cancer.

Objective: The primary objective of this study is to assess the feasibility of a 6-month physical activity intervention with activity trackers in patients with metastatic breast cancer (the Advanced stage Breast cancer and Lifestyle Exercise, ABLE Trial). Secondary objectives are to examine the effects of physical activity on physical, psychological, anthropometrics, clinical, and biological parameters.

Methods: We plan to conduct a single-center, single-arm trial with 60 patients who are newly diagnosed with metastatic breast cancer. Patients will receive an unsupervised and personalized 6-month physical activity program that includes an activity tracker Nokia Go and is based on the physical activity recommendation. Patients will be encouraged to accumulate at least 150 minutes per week of moderate-to-vigorous intensity physical activity. Baseline and 6-month assessments will include anthropometric measures, functional tests (eg, 6-minute walk test and upper and lower limb strength), blood draws, patient-reported surveys (eg, quality of life and fatigue), and clinical markers of tumor progression (eg, Response Evaluation Criteria In Solid Tumors criteria).

Results: Data collection occurred between October 2016 and January 2018, and the results are expected in August 2018.

Conclusions: The ABLE Trial will be the first study to assess the feasibility and effectiveness of an unsupervised and personalized physical activity intervention performed under real-life conditions with activity trackers in patients with metastatic breast cancer.

Trial Registration: ClinicalTrials.gov NCT03148886; https://clinicaltrials.gov/ct2/show/NCT03148886 (Accessed by WebCite at http://www.webcitation.org/71yabi0la).

Registered Report Identifier: RR1-10.2196/10487.
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http://dx.doi.org/10.2196/10487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137283PMC
August 2018

Transmission of breast cancer polygenic risk based on single nucleotide polymorphisms.

Breast 2018 Oct 14;41:14-18. Epub 2018 Jun 14.

Centre Paul Strauss, Porte de l'Hopital Strasbourg, France. Electronic address:

Aim: The goal of the present study was to further refine how polygenic risk scores may be used in a large population and to quantify the transmission of risk score through generations.

Methods: Allele frequencies from the 1000 Genomes data for 159 single nucleotide polymorphisms associated with breast cancer risk were used. A breast cancer risk score was calculated among 100,000 people. Choosing two "parents" and the alleles they transmit at random, 100,000 "daughters" were simulated. The population was divided by deciles of risk score. Comparing mean risk score in the mother and daughter populations provided information regarding the general relationship at a population level. By examining the distribution of daughter's risk score within each decile of maternal risk score, the transmission was evaluated at the subject level.

Results: Mean values of risk score were 85.1 (St Dev = 7.5) and 85.0 (St Dev = 7.5) for the populations of mothers and daughters, respectively (mean absolute difference = 0.02, p = 0.48). When examining the transmission of risk score from mothers to daughters in specific deciles of risk, statistically significant differences were observed in all deciles (ranged between 0.001 and < 2.2 × 10).

Conclusion: The relationship at the subject level will not provide information regarding prevention and screening of offspring based on the knowledge of parents' risk score alone. The present results show that risk estimation by polygenic risk scores is personal, and evaluation of risk score is required for each individual.
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http://dx.doi.org/10.1016/j.breast.2018.06.006DOI Listing
October 2018

Location of Mutation in Gene and Survival in Patients with Ovarian Cancer.

Clin Cancer Res 2018 01 30;24(2):326-333. Epub 2017 Oct 30.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France.

BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of gene affects the clinical outcome of ovarian cancer patients. A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for and genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer ( = 316) was used as a validation cohort. In the study cohort, 78 patients were carriers of germline mutations of After adjustment for FIGO stage and macroscopic residual disease, carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20-0.64; = 0.001] and prolonged PFI (29.7 vs. 15.5 months, = 0.011), compared with noncarriers. carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07; = 0.094) or PFI (19 vs. 15.5 months, = 0.146). In the TCGA cohort, only carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68; = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; = 0.001). Among ovarian cancer patients, carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-2136DOI Listing
January 2018

Survival impact of centralization and clinical guidelines for soft tissue sarcoma (A prospective and exhaustive population-based cohort).

PLoS One 2017 3;12(2):e0158406. Epub 2017 Feb 3.

Department of Medical Oncology, Centre Léon Bérard, Lyon, France.

Purpose: The outcome of sarcoma has been suggested in retrospective and non-exhaustive studies to be better through management by a multidisciplinary team of experts and adherence to clinical practice guidelines (CPGs). The aim of this prospective and exhaustive population based study was to confirm the impact of adherence to CPGs on survival in patients with localized sarcoma.

Experimental Design: Between 2005 and 2007, all evaluable adult patients with a newly diagnosis of localized sarcoma located in Rhone Alpes region (n = 634), including 472 cases of soft-tissue sarcoma (STS), were enrolled. The prognostic impact of adherence to CPGs on progression-free survival (PFS) and overall survival (OS) was assessed by multivariate Cox model in this cohort.

Results: The median age was 61 years (range 16-92). The most common subtypes were liposarcoma (n = 133, 28%), unclassified sarcoma (n = 98, 20.7%) and leiomyosarcoma (n = 69, 14.6%). In the initial management phase, from diagnosis to adjuvant treatment, the adherence to CPGs for patients with localized STS was 36% overall, corresponding to 56%, 85%, 96% and 84% for initial surgery, radiation therapy, chemotherapy and follow-up, respectively. Adherence to CPGs for surgery was the strongest independent prognostic factor of PFS, along with age, gender, grade, and tumor size. For OS, multivariate analysis adherence to CPGs for surgery was a strong independent prognostic factor, with an important interaction with a management in the regional expert centers.

Conclusions: This study demonstrates impact of CPGs and treatment within an expert center on survival for STS patients in a whole population-based cohort.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158406PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291382PMC
August 2017

Efficacy and safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer with brain metastases.

Breast Cancer Res Treat 2016 06 11;157(2):307-318. Epub 2016 May 11.

Medical Oncology Department, Institut Claudius Regaud, IUCT-Oncopole, 1 avenue Irène Joliot-Curie, 31059, Toulouse, France.

Few data are currently available regarding the efficacy and safety of T-DM1 in breast cancer (BC) patients with unselected brain metastases (BM), since most clinical trials have excluded BM patients or have only included highly selected patients. HER2 + BC patients with BM treated with T-DM1 in 5 French centers were included in this retrospective study. Clinical management was performed according to the product guidelines. Efficacy was evaluated recording tumor response rates, progression-free (PFS) and overall survival, treatment compliance, and safety. Thirty nine patients received T-DM1, among whom 82 % presented with concomitant extra-cerebral disease. Median number of previous metastatic chemotherapy and HER2-directed targeted therapy regimens was 2 (range 0-8) and 1 (0-7), respectively. Thirty six patients had received BM loco-regional treatment (72 % whole-brain radiation therapy). After a median follow-up of 8.1 months (1.4-39.6), 24 patients had progressed (first site of progression: brain 14; meningeal 2; outside of the central nervous system 5; both intra- and extra-cerebral 3), 12 patients had died (disease progression), and 27 patients were still alive. Median number of T-DM1 cycles was 8 (1-43). There were 17 partial responses (44 %) and 6 patients achieved disease stabilization (59 % clinical benefit rate). Median PFS was 6.1 months (95 %CI 5.2-18.3), with one- and two-year PFS rates of 33 and 17 %, respectively. Treatment was well tolerated, without unexpected toxicities, treatment delay, or dose reduction. In this retrospective study, T-DM1 appeared to be an effective and well-tolerated therapeutic option in unselected HER2 + BC patients with BM. These findings require a prospective validation.
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http://dx.doi.org/10.1007/s10549-016-3828-6DOI Listing
June 2016

[Trastuzumab emtansine in the systemic treatment of HER-2-positive breast cancer brain metastases].

Bull Cancer 2016 May 15;103(5):507-10. Epub 2016 Mar 15.

Centre Léon-Bérard, département d'oncologie médicale, 69008 Lyon, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2016.02.005DOI Listing
May 2016

[Initial management of advanced ovarian cancer: What radiological, pathological and surgical information are important for optimal therapeutic strategy?].

Bull Cancer 2015 Sep 28;102(9):772-9. Epub 2015 May 28.

Centre Léon-Bérard, département d'oncologie médicale, 69008 Lyon, France.

Because the majority of patients present advanced disease at diagnosis, the management of epithelial ovarian cancer needs specialist multidisciplinary teamwork. Expertise in surgery, chemotherapy, imaging and histopathology is essential to achieve optimum outcomes. Computed tomography scans are routinely used to determine the extent of disease and to aid in surgical planning. The histologic classification is crucial to plan the best therapeutic strategy and to define the prognosis of disease. Pathological prognostic factors, such as degree of differentiation, FIGO-stage, and histological type have to be described. This report is fundamental to assessing prognosis and selection of appropriate treatment strategy. An adequate staging procedure is an extensive staging by an experienced gynecological oncologist, exploring the entire upper abdomen, and the pelvic and para-aortic lymph node regions to define the Peritoneal Cancer Index (PCI). The final assessment is the completeness of cytoreduction (CC) score, which is an assessment of residual disease after a maximal surgical effort. Initial management of advanced ovarian cancer is best provided by a specialist multidisciplinary team, including a radiologist, a pathologist, a gynecologic oncologist and a medical oncologist.
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http://dx.doi.org/10.1016/j.bulcan.2015.04.011DOI Listing
September 2015

[New therapeutical strategies in metastatic hormone-dependent breast cancer].

Bull Cancer 2015 Apr 21;102(4):367-80. Epub 2015 Mar 21.

Centre Léon-Bérard, 69008 Lyon, France.

Hormone-dependent breast cancer is the first example of cancer treated by targeted therapy for more than 30 years. Blocking estrogen pathway was the first therapeutical strategy for this subtype of breast cancer, and remains the principle of current standard treatment. Despite the efficacy of drugs used in endocrine therapy, hormone resistance is a major problem for the management of patients with hormone-dependent breast cancer. In this review, we will discuss the development of strategies targeting the PI3K/Akt/mTOR pathway, CDK4/6 (Cyclin Dependent Kinase 4/6) and FGFR (Fibroblast Growth Factor Receptor) in hormone-dependent metastatic breast cancer (ER+). Recent results of clinical trials showed that combination of endocrine therapy with such pharmacological inhibitors is a promising strategy to overcome endocrine resistance. Mutated forms and isoforms of ERα have been recently discovered and its targeting could represent an therapeutic alternative. Future progress will focus on the identification of new compounds and combinations with other targeted therapies to improve the efficacy of such inhibitors in clinical practice.
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http://dx.doi.org/10.1016/j.bulcan.2015.02.013DOI Listing
April 2015

Therogenetics: transferring GWAS technology to the clinic.

Mutagenesis 2015 Mar;30(2):213-5

Université de Lyon, F-69000 Lyon, France, Université Lyon 1, F-69100 Villeurbanne, France, INSERM U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France and Centre Léon Bérard, F-69008 Lyon, France.

Molecular characteristics of breast tumours have been used for the last decades to guide clinicians in treating this devastating disease. More recent information has led to further refinement of molecular characteristics of breast tumours, and subsequent indications for specific treatments. However, evidence exists that factors independent of the primary tumour type, potentially germline genetics, may influence progression to metastasis. In this review, we expose some of this evidence, and propose tools needed to overcome current limitations to the identification of specific germline variants that influence risk of metastases in breast cancer patients.
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http://dx.doi.org/10.1093/mutage/geu060DOI Listing
March 2015

Territorial inequalities in management and conformity to clinical guidelines for sarcoma patients: an exhaustive population-based cohort analysis in the Rhône-Alpes region.

Int J Clin Oncol 2014 Aug 10;19(4):744-52. Epub 2013 Aug 10.

Centre Léon Bérard, 28 Rue Laennec, 69008, Lyon, France,

Background: Sarcomas are rare cancers with great variability in clinical and histopathological presentation. The main objective of clinical practice guidelines (CPGs) is to standardize diagnosis and treatment.

Methods: From March 2005 to February 2007, all patients diagnosed with localized sarcoma in the Rhône-Alpes region were included in a cohort-based study, to evaluate the compliance of sarcoma management with French guidelines in routine practice and to identify predictive factors for compliance with CGPs.

Results: 634 (71 %) patients with localized sarcoma satisfying the inclusion criteria were included out of 891 newly diagnosed sarcomas. Taking into account initial diagnosis until follow-up, overall conformity to CPGs was only 40 % [95 % confidence interval (CI) = 36-44], ranging from 54 % for gastrointestinal stromal tumor to 36 % for soft tissue sarcoma and 42 % for bone sarcoma. In multivariate analysis, primary tumor type [relative risk (RR) = 4.42, 95 % CI = 2.79-6.99, p < 0.001], dedicated multidisciplinary staff before surgery (RR = 4.19, 95 % CI = 2.39-7.35, p < 0.001) and management in specialized hospitals (RR = 3.71, 95 % CI = 2.43-5.66, p < 0.001) were identified as unique independent risk factors for conformity to CPGs for overall treatment sequence.

Conclusions: With only 40 % of total conformity to CPGs, the conclusions support the improvement of initial sarcoma management and its performance in specialized centres or within specialized dedicated networks.
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http://dx.doi.org/10.1007/s10147-013-0601-2DOI Listing
August 2014

Molecular characterization of anastrozole resistance in breast cancer: pivotal role of the Akt/mTOR pathway in the emergence of de novo or acquired resistance and importance of combining the allosteric Akt inhibitor MK-2206 with an aromatase inhibitor.

Int J Cancer 2013 Oct 2;133(7):1589-602. Epub 2013 May 2.

ISPB, Faculté de Pharmacie, Université Lyon 1, Lyon, France.

Acquisition of resistance to aromatase inhibitors (AIs) remains a major drawback in the treatment of estrogen receptor alpha (ERα)-positive breast cancers. The Res-Ana cells, a new model of acquired resistance to anastrozole, were established by long-term exposure of aromatase-overexpressing MCF-7 cells to this drug. These resistant cells developed ER-independent mechanisms of resistance and decreased sensitivity to the AI letrozole or to ERα antagonists. They also displayed a constitutive activation of the PI3K/Akt/mTOR pathway and a deregulated expression of several ErbB receptors. An observed increase in the phospho-Akt/Akt ratio between primary and matched recurrent breast tumors of patients who relapsed under anastrozole adjuvant therapy also argued for a pivotal role of the Akt pathway in acquired resistance to anastrozole. Ectopic overexpression of constitutively active Akt1 in control cells was sufficient to induce de novo resistance to anastrozole. Strikingly, combining anastrozole with the highly selective and allosteric Akt inhibitor MK-2206 or with the mTOR inhibitor rapamycin increased sensitivity to this AI in the control cells and was sufficient to overcome resistance and restore sensitivity to endocrine therapy in the resistant cells. Our findings lead to us proposing a model of anastrozole-acquired resistance based on the selection of cancer-initiating-like cells possessing self-renewing properties, intrinsic resistance to anastrozole and sensitivity to MK-2206. Altogether, our work demonstrated that the Akt/mTOR pathway plays a key role in resistance to anastrozole and that combining anastrozole with Akt/mTOR pathway inhibitors represents a promising strategy in the clinical management of hormone-dependent breast cancer patients.
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http://dx.doi.org/10.1002/ijc.28182DOI Listing
October 2013

[Antihormonal therapy in breast cancer and mTOR inhibitors].

Bull Cancer 2011 Dec;98(12):1431-7

Centre Léon-Bérard, oncologie médicale, Lyon, France.

Hormonal dependence of breast cancer has been known for a long time, yet about half of breast cancers with estrogen receptor will not respond to antihormonal therapy. Now, we know that this resistance may be related to a dysfunction of the estrogen pathway, or that of growth factors and particularly the pathway of cell activation PI3K/Akt/mTOR. Prevention of these different mechanisms of resistance could involve combination therapies such as anti-estrogens (SERMs, aromatase inhibitors) with inhibitors of the activity of growth factors that are particularly temsirolimus and everolimus for the activation pathway cell PI3K/Akt/mTOR.
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http://dx.doi.org/10.1684/bdc.2011.1496DOI Listing
December 2011

Outcome of recurrent and metastatic small cell carcinoma of the bladder.

BMC Urol 2009 Jun 6;9. Epub 2009 Jun 6.

Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco.

Background: Bladder small cell carcinoma is an uncommon tumour. Through a retrospective study we will present the evolution of recurrent and metastatic disease and outcome of patients treated at Léon-Bérard Cancer Centre.

Methods: Only 15 patients having recurrent or metastatic bladder small cell carcinoma were treated at Léon-Bérard Cancer Centre between 1996 and 2007. The patients were divided in two groups: a mixed small cell carcinoma group (9 patients) and a pure small cell carcinoma group (6 patients). All the records and informations related to treatment and outcome of the 15 patients were retrospectively analyzed. Various characteristics of small cell carcinoma were investigated.

Results: The median age of the 15 patients having recurrent or metastatic bladder small cell carcinoma and treated at Léon-Bérard Cancer Centre was 63 years and the disease was at stage IV for all cases. Nine patients were treated by chemotherapy. Four patients were treated by local radiotherapy (3 with radiotherapy without previous surgery and 1 with surgery followed by radiotherapy) and chemotherapy. One patient was treated by whole brain radiotherapy. And one patient died before treatment. After 52.4 months median follow up, 12 patients died. Median overall survival was 7.6 months. Survival probability at 1 year was 33%. Median overall survival was 9.9 months in the mixed small cell carcinoma group, and was only 4.6 months in the pure small cell carcinoma group. Survival probability at 1 year in the mixed small cell carcinoma group was 44% as compared to 17% in the pure small cell carcinoma group (Log-rank test: p = 0.228).

Conclusion: Recurrent and metastatic bladder small cell carcinoma is associated with very poor prognosis. The pure bladder small cell carcinoma appears to have poorer outcome than the mixed bladder small cell carcinoma. Chemotherapy using platinum drugs is a mainstay treatment.
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http://dx.doi.org/10.1186/1471-2490-9-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2700133PMC
June 2009

Small cell cancer of the bladder: The Leon-Berard cancer centre experience.

Indian J Urol 2008 Oct;24(4):494-7

Medical Oncology, Centre Léon-Bérard, 28, Rue Laennec, Lyon-69373 - France.

Background: Small cell bladder carcinoma is an uncommon tumor. In this retrospective study we report our experience dealing with this disease at the Leon-Berard Cancer Centre.

Materials And Methods: WE RETROSPECTIVELY ANALYZED VARIOUS CHARACTERISTICS OF SMALL CELL BLADDER CARCINOMA: patient demographics, histological diagnosis, disease stage, treatment effects and outcome, in 14 non-metastatic small cell bladder carcinoma patients treated at our institution between 1995 and 2006.

Results: The mean age at diagnosis was 60 years (range, 45-77). All patients were male. Seventy-five per cent were smokers. All had locally advanced disease. Ten patients (71.4%) were treated by cystoprostatectomy and bilateral pelvic lymph node resection, one by cystoprostatectomy alone. Two patients received neoadjuvant chemotherapy and four received adjuvant chemotherapy. One patient was treated by radiotherapy with concomitant cisplatin after transurethral resection of bladder tumor (TURBT). One patient refused surgery and was treated by chemotherapy alone. One patient was lost to follow-up after TURBT. After 49-month median follow-up, 12 patients had relapsed. Disease-free survival was 5.7 months. The most frequent sites of relapse were the retroperitoneal lymph node (seven patients) and the liver (three patients). Nine patients died of metastasis. Median overall survival was 29.5 months. Survival probability at two years was 58%. Median overall survival was 34 months in the mixed small carcinoma group, as compared with 9.5 months in the pure small cell carcinoma group (P=0.01). Mean overall survival was 27.2 months for all patients and 38.6 months for patients treated with cystectomy and adjuvant chemotherapy.

Conclusion: To date, the optimal treatment for locally advanced small cell bladder carcinoma is not clear. Cystectomy with neoadjuvant or adjuvant chemotherapy appears as a viable option.
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http://dx.doi.org/10.4103/0970-1591.44255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684383PMC
October 2008