Florence Rollot

Bacterial Floras and Biofilms of Malignant Wounds Associated with Breast Cancers

ABSTRACT The risk of infections and the appearance of symptoms (e.g., odors) represent the main troubles resulting from malignant wounds. The aim of this study was to characterize the balance of bacterial floras and the relationships between biofilms and bacteria and the emergence of symptoms. Experimental research was carried out for 42 days on malignant wounds associated with breast cancer. Investigations of bacterial floras (aerobes, aero-anaerobes, and anaerobes), detection of the presence of biofilms by microscopic epifluorescence, and clinical assessment were performed. We characterized biofilms in 32 malignant wounds associated with breast cancer and bacterial floras in 25 such wounds. A mixed group of floras, composed of 54 different bacterial types, was identified, with an average number per patient of 3.6 aerobic species and 1.7 anaerobic species; the presence of strict anaerobic bacterial strains was evidenced in 70% of the wounds; biofilm was observed in 35% of the cases. Odor was a reliable indicator of colonization by anaerobes, even when this symptom was not directly linked to any of the identified anaerobic bacteria. Bacteria are more likely to be present during myelosuppression and significantly increase the emergence of odors and pain when present at amounts of >105 · g−1. The presence of biofilms was not associated with clinical signs or with precise types of bacteria. No infections occurred during the 42-day evaluation period. This study provides a dynamic description of the bacterial floras of tumoral wounds. The study results highlight the absolute need for new therapeutic options that are effective for use on circulating bacteria as well as on bacteria organized in biofilm.

Biofilm et plaies

Le biofilm est une organisation bacterienne particuliere. Des bacteries initialement circulantes adherent au lit de la plaie et se regroupent de facon structuree grâce a un procede de communication interbacterienne appele quorum sensing . Elles vont alors synthetiser une matrice tridimensionnelle qui les protege des antiseptiques et des antibiotiques. Sur les plaies, la presence de biofilm retarde le processus de cicatrisation et majore le risque d’infections. La suspicion de biofilm est evoquee face a une plaie qui n’evolue pas favorablement malgre des soins adaptes. Une detersion repetee associee a l’application d’antimicrobien ou antibiofilm semble la strategie la plus efficace.

330TiPASTER 70S UNICANCER PHASE III TRIAL : ADJUVANT TREATMENT FOR WOMEN OVER 70 WITH LUMINAL BREAST CANCER

ABSTRACT Background: Benefit of the additional adjuvant chemotherapy (CT) compared with hormonal therapy alone (HT) remains debated for women >70 with ER+ HER2- breast cancer (BC) and aggressive characteristics. This trial compares the impact of both strategies on overall survival (OS). Trial design: Following surgery, ∼2,000 patients (Pts) will have a Genomic Grade (GG) performed centrally on FFPE specimens by RT-PCR. Those with a high risk defined as high or equivocal GG will be randomized to HT alone vs CT + HT. Pts with a low GG will be followed as an observational cohort. OS (all deaths) is the primary endpoint. Secondary objectives include competing events, cost-effectiveness and Q-TWiST analysis, geriatric dimension, willingness and health-related quality of life including specific ELD15. Translational research will focus on prognostic biomarkers and pharmacogenetics. Sample size based on an expected 4-year OS benefit (87.5 vs 80%; HR 0.60), with bilateral test a = 0.05 and a statistical power of 80%. It will require to observe 129 events and to randomize 700 Pts over a planned duration of 4 years. As of March 2014, 65 centres in France and Belgium have included 890 Pts aged 70-92. Only 30 GG evaluations were not performed (consent withdrawal, 7; tumour blocks not available, 14; central pathology review discordance, 6; treatment choice, 3). In the main participating site, the study was not proposed to 20% of pre-screened Pts mostly because of team choice (50%) and inclusion criteria (25%). Amongst those informed, 66% accepted to participate.). Overall, of 860 cases with GG report, 346 (41%), 167 (19%) and 338 (39%) were low, equivocal and high GG respectively; 9 tests (1%) failed for technical reasons. The proportion of high risk tumours (high + equivocal GG, 59%) is similar to those observed in general BC populations (40% to 60%) and only 19 of high-risk cases were not randomized (consent withdrawal, 6, distant metastases, 3, treatment choice, 5, tumour phenotype not confirmed, 3, or laboratory values, 2). With 69% of target recruitment at mid-term of the planned inclusion period, we confirm the feasibility of such a multicentre program investigating the role of an innovative prognostic signature to better select adjuvant strategy in the elderly BC population. Disclosure: H. Peyro Saint Paul: employee and stock holder QIAGEN. All other authors have declared no conflicts of interest.

Abstract OT3-1-10: ASTER 70s (UNICANCER phase III trial): Is personalized adjuvant treatment for women over 70 with luminal breast cancer the way to go?

Background The question of the additional benefit of adjuvant chemotherapy (CT) compared to hormonal therapy alone (HT) for women >70 with ER+ / HER2- breast cancer (BC) and aggressive characteristics is still unsolved. This trial compares the impact of both strategies on overall survival (OS). Trial design Following surgery, ∼2,000 patients will have a Genomic Grade (GG) centrally performed on FFPE specimens. Those with a high or equivocal GG will be randomized HT alone vs HT+CT. Patients with low GG will be followed as an observational cohort. The study, on-going in France since April 2012, has been recently activated in Belgium. Eligibility criteria Any ER+ HER2- BC after complete surgery, M0, any pT or pN. Normal organ functions. No specific BC treatment before surgery. Contralateral BC, invasive BC after ductal carcinoma in situ and isolated local invasive relapse when adjuvant systemic treatment is considered are all eligible. Multifocal or bilateral are eligible according to focus with worst GG. The G8 screening tool is used as stratification criteria for randomization. Specific aims OS (all deaths) is the primary endpoint. Secondary objectives include competing events, cost-effectiveness and Q-TWiST analysis, geriatric dimension, acceptability/willingness and health-related quality of life including specific ELD15. The Lee9s 4-year mortality score is calculated. Translational research will focus on prognostic biomarkers and pharmacogenetic, investigating also the impact of treatments on putative ageing biomarkers as CRAMP, stathmin, EF-1α and chitinase and telomeres length. Statistical methods Sample size based on 4-year OS (87.5 vs 80%), bilateral test, α = 0.05, β = 0.20 and HR = 0.60. In total, 129 events are expected, requiring 340 patients/arm. Considering those lost to follow-up, ∼700 patients in total should be included (5 extra patients/year). Present accrual and target accrual As of May 2013, 43 centres have included 406 Patients aged 70-88. Only 14 GG evaluations were not performed for the following reasons: Patients consent withdrawal (n = 3), tumour block not available for the GG test (n = 5), CT not a treatment option anymore (patients or investigator9s decision) (n = 2) or tumour status (ER+/HER2-) not confirmed by central review (n = 4). 8 GG evaluations are on-going. Of 384 cases with GG report, 160 (42%), 151 (39%) and 65 (17%) were respectively GG-1 (low risk), GG-3 (high risk) and GG-EQ (equivocal); 8 (2%) tests failed for technical reasons. The proportion of high GG in the study (53%) is similar to those observed in previous studies in general BC populations (40% to 60%). Of 216 GG-3/-EQ cases, 4 were not randomized because of distant metastases detected during extensive work-up (n = 3) and Patient refusal of CT treatment before randomization (n = 1). Five randomizations are on-going. GG determination was obtained in 384 leading to randomization in 207, totalizing so far 30% of the projected recruitment for the primary objective. This confirms the feasibility of such multicentre strategic program with an innovative prognostic signature in the elderly BC population. Contact information c-orsini@unicancer.fr. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-1-10.