TORSAFUF - Surgical exploration for torsion of spermatic cord suspicion and risk factors for unnecessary surgery: Results of a French nationwide retrospective study on 2940 patients.

BACKGROUNDS: Spermatic cord torsion is a frequent urological emergency that mostly concerns teenagers and young adults. This study aimed to determine the clinical and surgical characteristics of young adults who had scrotal exploration for suspected spermatic cord torsion and to identify clinical risk factors associated with needless scrotal exploration. METHODS: We retrospectively collected national data from patients aged 12years and older who underwent a surgical exploration for suspicion of torsion of the spermatic cord between 2005 and 2019 in 17 hospitals. We analyzed demographics, surgical and postoperative characteristics in our population. We compared the cohort according to the intraoperative diagnosis of torsion or not. RESULTS: In total, 2940 had surgical exploration: 1802 (61.3%) patients had torsion of the spermatic cord and 1138 (38.7%) had another diagnosis. In multivariate analysis, age (OR: 1.04; 95% CI: 1.01-1.06; P=0.005), medical history of cryptorchism (OR: 4.14; 95% CI: 1.05-16.31; P=0.042) and VAS pain score (OR: 0.91; 95% CI: 0.83-0.98; P=0.018) were risk factors significantly associated with unnecessary surgical exploration. The rate of complications in the 90days after surgery was 11% in the "torsion" group, and 9.7% in the "non-torsion" group (P=0.28). CONCLUSION: Scrotal exploration without intraoperative diagnosis of torsion was performed in 40% of our cohort. VAS pain score and cryptorchism history can help for the diagnosis but scrotal exploration remains the way to diagnose spermatic cord torsion and should be performed on the slightest suspicion, even after 24hours of symptoms, as the chances for testicular salvage remains around 50%.

[Impact of positive surgical margins on prostate cancer prognosis]. / Impact carcinologique des marges positives après prostatectomie totale.

OBJECTIVE: To examine the impact of positive surgical margins (PSM) after radical prostatectomy (RP) for prostate cancer on oncological results. PATIENTS AND METHODS: We performed a study where all patients who underwent radical prostatectomy between January 2004 and December 2018 for prostate cancer were included. The preoperative, postoperative data and the carcinological results collected were analyzed. Data were analysed using Kaplan-Meier survival analysis and proportional hazards models. RESULTS: A total of 319 patients with a median age of 65 years (IQR : 62-69) were included. The median follow-up was 43.6 months (IQR: 19.4-79.3). The overall rate of PSM was 33.5%. PSM was associated with biochemical recurrence (P<0.001). Overall mortality was not associated with positive margins. A clinical stage> T1c was an independent predictor of PSM on multivariate analysis (P=0.01). CONCLUSION: PSM would increase the risk of biochemical recurrence with no impact on survival. Clinical stage>T1c was an adverse predictor for PSM. LEVEL OF EVIDENCE: 3.

Characterization of the pathogenicity of strains of Pseudomonas syringae towards cherry and plum.

Bacterial canker is a major disease of Prunus avium (cherry), Prunus domestica (plum) and other stone fruits. It is caused by pathovars within the Pseudomonas syringae species complex including P. syringae pv. morsprunorum (Psm) race 1 (R1), Psm race 2 (R2) and P. syringae pv. syringae (Pss). Psm R1 and Psm R2 were originally designated as the same pathovar; however, phylogenetic analysis revealed them to be distantly related, falling into phylogroups 3 and 1, respectively. This study characterized the pathogenicity of 18 newly genome-sequenced P. syringae strains on cherry and plum, in the field and laboratory. The field experiment confirmed that the cherry cultivar Merton Glory exhibited a broad resistance to all clades. Psm R1 contained strains with differential specificity on cherry and plum. The ability of tractable laboratory-based assays to reproduce assessments on whole trees was examined. Good correlations were achieved with assays using cut shoots or leaves, although only the cut shoot assay was able to reliably discriminate cultivar differences seen in the field. Measuring bacterial multiplication in detached leaves differentiated pathogens from nonpathogens and was therefore suitable for routine testing. In cherry leaves, symptom appearance discriminated Psm races from nonpathogens, which triggered a hypersensitive reaction. Pathogenic strains of Pss rapidly induced disease lesions in all tissues and exhibited a more necrotrophic lifestyle than hemibiotrophic Psm. This in-depth study of pathogenic interactions, identification of host resistance and optimization of laboratory assays provides a framework for future genetic dissection of host-pathogen interactions in the canker disease.

To which mixtures are French pregnant women mainly exposed? A combination of the second French total diet study with the EDEN and ELFE cohort studies.

Pregnant women and their unborn child are exposed to a large number of substances during pregnancy. Some of these substances may cross the placenta, resulting in exposure of the foetus. There is growing evidence that certain substances could interact to produce a mixture effect. It is therefore essential to identify the main mixtures mothers are exposed to. This study aimed to identify the major mixtures French pregnant women included in EDEN and ELFE cohorts were exposed to, on the basis of the 441 substances analysed in the second French total diet study. Exposure systems and the composition of substances were identified from co-exposures using sparse non-negative matrix under-approximation to generate the main mixtures. Individuals were clustered to define clusters with similar co-exposure profiles. Six clusters associated with eight mixtures were identified. For example in ELFE, cluster 2 comprising 10% of the population was characterised by mixtures "Pest-1" mainly contains pesticides and "TE-F-PAH″ contains trace elements, furans and polycyclic aromatic hydrocarbons. Five other clusters were also described with their associated mixtures. Similar results were observed for EDEN. This study helps to prioritise mixtures for which it is crucial to investigate possible toxicological effects and to recommend epidemiological studies concerning health effects.

Dietary exposure to benzoates (E210-E213), parabens (E214-E219), nitrites (E249-E250), nitrates (E251-E252), BHA (E320), BHT (E321) and aspartame (E951) in children less than 3 years old in France.

This study aimed to estimate the exposure to seven additives (benzoates, parabens, nitrites, nitrates, BHA, BHT and aspartame) in children aged less than 3 years old in France. A conservative approach, combining individual consumption data with maximum permitted levels, was carried out for all the additives. More refined estimates using occurrence data obtained from products' labels (collected by the French Observatory of Food Quality) were conducted for those additives that exceeded the acceptable daily intake (ADI). Information on additives' occurrence was obtained from the food labels. When the ADI was still exceeded, the exposure estimate was further refined using measured concentration data, if available. When using the maximum permitted level (MPL), the ADI was exceeded for benzoates (1.94 mg kg(-1) bw day(-1)), nitrites (0.09 mg kg(-1) bw day(-1)) and BHA (0.39 mg kg(-1) bw day(-1)) in 25%, 54% and 20% of the entire study population respectively. The main food contributors identified with this approach were current foods as these additives are not authorised in specific infant food: vegetable soups and broths for both benzoates and BHA, delicatessen and meat for nitrites. The exposure estimate was significantly reduced when using occurrence data, but in the upper-bound scenario the ADI was still exceeded significantly by the age group 13-36 months for benzoates (2%) and BHA (1%), and by the age group 7-12 months (16%) and 13-36 months (58%) for nitrites. Measured concentration data were available exclusively for nitrites and the results obtained using these data showed that the nitrites' intake was below the ADI for all the population considered in this study. These results suggest that refinement of exposure, based on the assessment of food levels, is needed to estimate the exposure of children to BHA and benzoates for which the risk of exceeding the ADI cannot be excluded when using occurrence data.

Rapid identification of the genus Dekkera/Brettanomyces, the Dekkera subgroup and all individual species.

The genus Dekkera/Brettanomyces comprises five described species: Dekkera bruxellensis, D. anomala, Brettanomyces custersianus, B. naardenensis and B. nanus. Some of them, especially D. bruxellensis, are important spoilage organisms, particularly in the wine and beverage industries. Because of their economic importance many different methods have been developed to identify members of the genus in general and D. bruxellensis in particular. These methods vary in their rapidity, complexity and cost but, partly because of confidentiality issues, it is unclear which methods are used, or how widely, in the relevant industries. Building on previous work with the genera Saccharomyces and Zygosaccharomyces, a suite of eight PCR primer pairs has been designed either on the D1-D2 region of the 26S rRNA gene or translation elongation factor TEF1-α. These primers can specifically identify the genus as a whole, only Dekkera species, each one of the five recognised species as well as a significant subgroup of D. bruxellensis represented by NCYC 3426. Multiplexing has also been tried and it has been shown to be possible with some combinations of genus or Dekkera-level and species-specific primers. Using direct colony PCR amplification followed by gel electrophoresis, a clear positive result can be obtained in less than 3h, thus providing a quick, reliable and inexpensive way to identify target species.

Assessment of infant exposure to food chemicals: the French Total Diet Study design.

As part of the previous French Total Diet Studies (TDS) focusing on exposure to food chemicals in the population aged 3 years and older, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) launched a specific TDS on infants to complete its overall chemical food safety programme for the general population. More than 500 chemical substances were analysed in food products consumed by children under 3 years old, including nutrients, several endocrine disruptors resulting from human activities (polychlorinated biphenyls, dioxins and furans, brominated flame retardants, perfluoroalkyl acids, pesticide residues, etc.) or migrating from food contact materials such as bisphenol A or phthalates, but also natural substances such as mycotoxins, phytoestrogens and steroids. To obtain a representative and general view of infant food consumption, food items were selected based on results of a national consumption survey conducted specifically on this population. Moreover, a specific study on food was conducted on 429 households to determine which home-cooking practices are employed to prepare food consumed by infants. Overall, the targeted chemical substances were analysed in more than 450 food samples, representing the purchase and home-cooking practices of over 5500 food products. Foods included common foods such as vegetables, fruit or cakes as well as specific infant foods such as infant formula or jarred baby food. The sampling plan covered over 80% of the total diet. Specificities in infant food consumption and habits were therefore considered to define this first infant TDS. This study, conducted on a large scale and focusing on a particularly sensitive population, will provide accurate information on the dietary exposure of children under 3 years to food chemicals, especially endocrine disruptors, and will be particularly useful for risk assessment analysis under the remit of ANSES' expert committees.

Urinary S-PMA related to indoor benzene and asthma in children.

INTRODUCTION: Benzene is a ubiquitous pollutant of both indoor and outdoor environments which impacts on respiratory health. Our aim was to relate urinary S-phenylmercapturic acid (S-PMA), a biomarker of benzene exposure, to benzene concentrations and related sources at home and asthma in a population-based sample of children. METHODS: Exposure to benzene was assessed in the dwellings of 63 children (32 asthmatics and 31 controls) through the identification of sources of benzene and in situ assessments with passive samplers. The determination of urinary S-PMA was obtained by liquid chromatography-mass spectrometry. RESULTS: At home, asthmatics were significantly more polluted by benzene levels from ambient sampling than controls (p ≤ 0.05). Benzene exposure significantly aggravated asthma symptoms overall in non-atopic children (OR = 10.10; 95% confidence interval: 10.10). Urinary S-PMA was significantly associated with benzene concentrations in the entire population (regression coefficient = 0.28, 95% CI: 0.07-0.49; p < 0.05) and asthma (OR = 7.69; 95% CI: 1.37-42.52 for an increase of 1 µg/g creatinine of urinary S-PMA). However, after adjustment for environmental tobacco smoking exposure, familial allergy, age and sex, the latter relationship was no more significant (OR = 4.95; 95% CI: 0.91-27.4, p < 0.10). Both benzene concentrations and urinary S-PMA concentrations were higher in dwelling built after 1948 and in flats. CONCLUSIONS: Our study suggests a relationship between childhood asthma and benzene concentrations at home, even at low levels of this pollutant. This was confirmed when considering urinary S-PMA, which was related to both benzene concentrations and asthma. Further epidemiological and toxicological studies are needed to confirm our results.

Positive associations between respiratory outcomes and fungal index in rural inhabitants of a representative sample of French dwellings.

Our study aims at estimating exposure to molds at home, based on microbial Volatile Organic Compounds (MVOCs) assessment, and evaluating its effect on respiratory diseases in a representative sample of dwellings. In the framework of a national campaign, indoor pollution was monitored in a sample of the 24 million dwellings of metropolitan France (n=567). 727 subjects answered to a standardized questionnaire on respiratory diseases and had MVOCs sampled in their bedrooms and a fungal index (FI) defined. Among the 431 dwellings with complete data, one out of three was contaminated by molds as assessed by a positive FI: 27.0% in urban, 38.2% in periurban and 34.9% in rural dwellings respectively. Positive associations were observed between fungal index and current asthma (8.6%) and chronic bronchitis-like symptoms (8.4%), especially in rural areas (OR=2.95, 95%CI (1.10; 7.95) and 3.35, 95%CI (1.33; 8.48) respectively). Our study, based on objective assessments of fungal contamination, is in agreement with previous results suggesting mold-related respiratory effects. Moreover associations found among rural population could indicate specific pollution and impact in this environment.

[Allergic diseases in children and farming environment]. / Allergies et asthme chez l'enfant en milieu rural agricole.

INTRODUCTION: Children living in rural areas had lower prevalence of allergies than children from cities, in relation to farming exposure. STATE OF ART: Exposure to farm animals and consumption of raw milk appear to play an important role in the protection afforded by the agricultural environment, and this at different stages of child development. The mechanisms involved in these effects are still controversial, and recent publications cast doubt on the role of endotoxins initially suggested. It seems that exposure to indoor air pollution, characterized by excessive biocontaminants (mold, allergens…) is a key element in the development of allergic diseases. PERSPECTIVES: The establishment of cohort studies, a better assessment of exposure to pollution at home but also in farm buildings and the study of gene-environment interactions should improve the knowledge on the protective effect towards allergy of farming environment. CONCLUSIONS: The farming environment, very specific, could be an important model for better understanding the mechanisms involved in allergic and respiratory diseases. In addition, urbanization and thus reduction of the rural environment, may well explain the increased prevalence of allergies observed in the past 50 years.

Indoor air pollution and childhood asthma: variations between urban and rural areas.

UNLABELLED: Health effects of indoor pollution have been investigated overall in urban areas. To compare the potential effect of home air pollutants on asthma in urban and rural houses, two case-control populations, composed of children living in the city (32 asthmatics and 31 controls) and in the countryside (24 asthmatics and 27 controls) were included. During 1 week, nitrogen dioxide, fine particles, and volatile organic compounds (formaldehyde, acetaldehyde, benzene, toluene, ethylbenzene, and xylenes) were assessed at home. Urban dwellings were found to be more polluted than rural ones, with concentrations up to two times higher. In the whole population, exposure to acetaldehyde and toluene was significantly associated with a higher risk of asthma. In the urban population, the association with toluene was significant in children studied during winter, and with toluene, xylenes, and ethylbenzene when cases were restricted to current asthmatics. In rural settings, a relationship between asthma and formaldehyde exposure was observed (OR = 10.7; 95% CI 1.69-67.61). Our findings suggest that daily continuous exposures to pollutants may be implicated in asthma, even in the case of low exposure, as those found in rural areas. Our results could also indicate a specific effect of indoor pollution in the rural environment. PRACTICAL IMPLICATIONS: Everyday exposure to indoor pollution was associated with a higher risk of childhood asthma. These findings suggest that even at low concentrations, pollutants could be implicated in asthma and reinforce the importance of establishing guideline values to improve indoor air quality by limiting sources or by optimizing ventilation. Specific effects could occur in rural environments where pollution differs from urban area.

Identification of biological factors predictive of response to imatinib mesylate in aggressive fibromatosis.

BACKGROUND: Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown. METHODS: We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of KIT exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors. RESULTS: Of 10 patients for whom DNA could be extracted, 3 had a KIT exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1-2) did not correlate with PFS. Pre-treatment lymphopenia (<1500/microl) and tumour size >120 mm correlated with shorter PFS in univariate and multivariate analyses. CONCLUSION: Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained.

Neo/adjuvant chemotherapy does not improve outcome in resected primary synovial sarcoma: a study of the French Sarcoma Group.

BACKGROUND: There are only scarce data about the benefit of adjunctive chemotherapy in patients with localized synovial sarcoma (SS). PATIENTS AND METHODS: Data from 237 SS patients recorded in the database of the French Sarcoma Group were retrospectively analyzed. The respective impact of radiotherapy, neo-adjuvant chemotherapy and adjuvant chemotherapy on overall survival (OS), local recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were assessed after adjustment to prognostic factors. RESULTS: The median follow-up was 58 months (range 1-321). Adjuvant, neo-adjuvant chemotherapy and postoperative radiotherapy were administered in 112, 45 and 181 cases, respectively. In all, 59% of patients treated with chemotherapy received an ifosfamide-containing regimen. The 5-year OS, LRFS and DRFS rates were 64.0%, 70% and 57%, respectively. On multivariate analysis, age >35 years old, grade 3 and not-R0 margins were highly significant independent predictors of worse OS. After adjustment to prognostic factors, radiotherapy significantly improved LRFS but not DRFS or OS. Neither neo-adjuvant nor adjuvant chemotherapy had significant impact on OS, LRFS or DRFS. CONCLUSION: As for other high-grade soft-tissue sarcomas, well-planned wide surgical excision with adjuvant radiotherapy remains the cornerstone of treatment for SS. Neo-adjuvant or adjuvant chemotherapy should not be delivered outside a clinical trial setting.

Practical guidance for the management of aromatase inhibitor-associated bone loss.

BACKGROUND: Recent studies indicate that women with breast cancer are at increased risk of fracture compared with their age-matched peers. Current treatment guidelines are inadequate for averting fractures in osteopenic women, especially those receiving aromatase inhibitor (AI) therapy. Therefore, we sought to identify clinically relevant risk factors for fracture that can be used to assess overall fracture risk and to provide practical guidance for preventing and treating bone loss in women with breast cancer receiving AI therapy. METHODS: Systematic review of pertinent information from published literature and meeting abstracts through December 2007 was carried out to identify factors contributing to fracture risk in women with breast cancer. An evidence-based medicine approach was used to select risk factors that can be used to determine when to initiate bisphosphonate treatment of aromatase inhibitor-associated bone loss (AIBL). RESULTS: Fracture risk factors were chosen from large, well-designed, controlled, population-based trials in postmenopausal women. Evidence from multiple prospective clinical trials in women with breast cancer was used to validate AI therapy as a fracture risk factor. Overall, eight fracture risk factors were validated in women with breast cancer: AI therapy, T-score <-1.5, age >65 years, low body mass index (BMI <20 kg/m(2)), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking. Treatment recommendations were derived from randomized clinical trials. CONCLUSIONS: The authors recommend the following for preventing and treating AIBL in women with breast cancer. All patients initiating AI therapy should receive calcium and vitamin D supplements. Any patient initiating or receiving AI therapy with a T-score >/=-2.0 and no additional risk factors should be monitored every 1-2 years for change in risk status and bone mineral density (BMD). Any patient initiating or receiving AI therapy with a T-score <-2.0 should receive bisphosphonate therapy. Any patient initiating or receiving AI therapy with any two of the following risk factors-T-score <-1.5, age >65 years, low BMI (<20 kg/m(2)), family history of hip fracture, personal history of fragility fracture after age 50, oral corticosteroid use >6 months, and smoking-should receive bisphosphonate therapy. BMD should be monitored every 2 years, and treatment should continue for at least 2 years and possibly for as long as AI therapy is continued. To date, the overwhelming majority of clinical evidence supports zoledronic acid 4 mg every 6 months to prevent bone loss in women at high risk. Although there is a trend towards fewer fractures with zoledronic acid, studies completed to date have not been designed to capture significant differences in fracture rate, and longer follow-up is needed.

Phase II multicenter study of larotaxel (XRP9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy.

BACKGROUND: Treatment options are limited for patients with refractory metastatic breast cancer (MBC). Larotaxel (XRP9881) is a novel taxoid with preclinical activity against taxane-resistant breast cancer. The current phase II trial of larotaxel was conducted in women with taxane-treated MBC. PATIENTS AND METHODS: Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m(2) was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated. RESULTS: One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%). CONCLUSIONS: Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC.

Oligonucleotide microarray analysis of estrogen receptor alpha-positive postmenopausal breast carcinomas: identification of HRPAP20 and TIMELESS as outstanding candidate markers to predict the response to tamoxifen.

The estrogen receptor alpha (ER alpha) status of breast tumors is used to identify patients who may respond to endocrine agents such as tamoxifen. However, ER alpha status alone is not perfectly predictive, and there is a pressing need for more reliable markers of endocrine responsiveness. In this aim, we used a two-step strategy. We first screened genes of interest by a pangenomic 44 K oligonucleotide microarray in a series of ten ER alpha-positive tumors from five tamoxifen-treated postmenopausal patients who relapsed (distant metastasis) and five tamoxifen-treated postmenopausal patients who did not relapse, matched with respect to age, Scarff-Bloom-Richardson grade, lymph node status, and macroscopic tumor size. Genes of interest (n=24) were then investigated in an independent well-characterized series of ER alpha-positive unilateral invasive primary breast tumors from postmenopausal women who received tamoxifen alone as adjuvant hormone therapy after primary surgery. We identified four genes (HRPAP20, TIMELESS, PTPLB, and MGC29814) for which high mRNA levels were significantly associated with shorter relapse-free survival (log-rank test). We also showed that hormone-regulated proliferation-associated 20 kDa protein (HRPAP20) and TIMELESS are 17beta-estradiol-regulated in vitro and are ectopically expressed in OH-Tam-resistant cell lines. In conclusion, these findings point to HRPAP20 and TIMELESS as promising markers of tamoxifen resistance in women with ER alpha-positive breast tumors.

Response to neoadjuvant chemotherapy in lobular and ductal breast carcinomas: a retrospective study on 860 patients from one institution.

BACKGROUND: We compared the impact of neoadjuvant chemotherapy on pathologic response and outcome in operable invasive lobular breast carcinoma (ILC) and invasive ductal breast carcinoma (IDC). PATIENTS AND METHODS: We extracted from our database all patients with pure invasive lobular (n=118, 14%) or pure invasive ductal carcinomas (n=742, 86%). Their treatment included neoadjuvant chemotherapy, adapted surgery, radiotherapy and adjuvant hormonal treatment. RESULTS: Compared with IDC, ILC presented with larger tumors (T3: 38.1% versus 21.4%, P=0.0007), more N0 nodes status (55.9% versus 43.3%, P=0.01), less inflammatory tumors (5.9% versus 11.8%, P=0.01), more hormone receptor positivity (65.5% versus 38.8%), lower histological grade (P<0.0001). Final surgery was a mastectomy in 70% of patients with ILC (34% were reoperated after initial partial mastectomy) and in 52% of IDC after 8% of reoperation (P=0.006). A pathological complete response (pCR) was achieved in 1% of ILC and 9% of IDC (P=0.002). The outcome at 60 months was significantly better for ILC, but histologic type was not an independent factor for survival in multivariate analysis. CONCLUSIONS: ILC appeared less responsive to chemotherapy but presented a better outcome than IDC. While new information on biological features of ILC is needed, we consider that neoadjuvant endocrine therapy in hormone receptor-positive ILC may be a more adapted approach than neoadjuvant chemotherapy.

How to maximize the efficacy of taxanes in breast cancer.

The life-expectancy of women with metastatic breast cancer (MBC) is closely linked to response to therapy. A significant increase in progression-free survival (PFS) and overall survival (OS) has been demonstrated in women who achieve a complete response. Anthracycline combinations have been proven as highly effective in MBC, and anthracycline regimens plus cyclophosphamide with or without fluorouracil were established as first-line chemotherapy for MBC in the 1990s. Clinical trials have shown that anthracycline-taxane combinations are more effective than anthracyclines or taxanes alone in terms of overall response rates (ORR), PFS and OS in women who have not received prior anthracycline chemotherapy. The use of anthracycline-based regimens is limited, however, by the widespread use of anthracycline adjuvant therapy and the development of anthracycline-resistance. Platinum-taxane combinations have similar efficacy to anthracycline-based regimens and are well-tolerated by patients. Carboplatin combined with paclitaxel or docetaxel is more effective than carboplatin or taxanes alone, with ORR of 53-62%. Taxane combinations with gemcitabine or capecitabine are also more effective than docetaxel, paclitaxel, capecitabine or gemcitabine administered alone. The efficacy of docetaxel and paclitaxel can be increased, and drug-related toxicity decreased, by adapting dose-dense schedules of drug administration. The addition of trastuzumab to taxane-based chemotherapy increases the efficacy of taxane-based regimens in women with HER2-positive MBC.

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer.

The purpose of the study was to evaluate the efficacy and safety of docetaxel plus epirubicin (ET) and of 5-fluorouracil plus epirubicin and cyclophosphamide (FEC) as first-line chemotherapy for metastatic breast cancer. A total of 142 patients (intent-to-treat (ITT)) with at least one measurable lesion were randomised to receive docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2) or 5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles. Prophylactic granulocyte-colony-stimulating factor was only permitted after the first cycle, if required. Per-protocol analysis (n=132) gave an overall response rate for ET of 63.1% (95% confidence interval (CI), 50-78%) and for FEC 34.3% (95% CI, 23-47%) after a median seven and six cycles, respectively. Intent-to-treat population (n=142) gave an overall response rate for ET of 59% (95% CI, 47-70%) and for FEC 32% (95% CI, 21-43%) after a median seven and six cycles, respectively. The median response duration for ET was 8.6 months (95% CI, 7.2-9.6 months) and for FEC 7.8 months (95% CI, 6.5-10.4 months). The median time to progression (ITT) for ET was 7.8 months (95% CI, 5.8-9.6 months) and for FEC 5.9 months (95% CI, 4.6-7.8 months). After a median follow-up of 23.8 months, median survival (ITT) for ET and FEC were 34 and 28 months, respectively. Nonhaematologic grade 3-4 toxicities were infrequent in both arms. Haematologic toxicity was more common with ET and febrile neutropenia was reported in 13 patients (18.6%) in the ET group. Two deaths in the ET group were possibly related to study treatment. In conclusion, both ET and FEC were associated with acceptable toxicity. ET is a highly active first-line therapy for metastatic breast cancer.