Investigating sexual health after breast cancer by longitudinal assessment of patient-reported outcomes.

BACKGROUND: Sexual concerns are a major unaddressed need among survivors of breast cancer (BC) with significant negative effects on quality of life. We longitudinally analyzed sexual health over time, using patient-reported outcomes. METHODS: Patients with stage I-III BC prospectively included from the CANcer TOxicity cohort (CANTO) provided data at diagnosis, then 1, 2, and 4 years afterward. Sexual concerns outcomes included poor body image (score ≤91/100), poor sexual functioning (≤16/100), poor sexual enjoyment (≤66/100), and sexual inactivity (EORTC QLQ-B23). Multivariate generalized estimating equation models assessed associations with sexual concerns after diagnosis, adjusting for age, sociodemographic, tumor, treatment, and clinical characteristics. RESULTS: Nearly 78.1% among 7895 patients reported at least one sexual concern between diagnosis and 4 years' follow-up. Over time, the proportion of patients reporting sexual concerns either increased or remained constant with diagnosis. Less than half (46%, range 11.4-57) of the patients with sexual concerns reported the use of supportive care strategies, including gynecological or psychological consultations (range 11.4-57.4). Factors consistently associated with sexual concerns up to 4 years after diagnosis included already reporting the same concern at diagnosis [odds ratio (OR)poor body image 3.48 [95% confidence interval (CI) 3.11-3.89]; ORsexual inactivity 9.94 (95% CI 8.84-11.18), ORpoor sexual function 9.75 (95% CI 8.67-10.95), ORpoorsexual enjoyment 3.96 (95% CI 3.34-4.69)], endocrine therapy use [ORpoor body image 1.15 (95% CI 1.01-1.31); ORsexual inactivity 1.19 (95% CI 1.02-1.39), ORpoor sexual function 1.17 (95% CI 1.01-1.37), ORpoor sexual enjoyment 1.23 (95% CI 1.00-1.53)], and depression [ORpoor body image 2.00 (95% CI 1.72-2.34); ORsexual inactivity 1.66 (95% CI 1.40-1.97), ORpoor sexual function 1.69 (95% CI 1.43-2.00), ORpoor sexual enjoyment 1.94 (95% CI 1.50-2.51)]. Outcome-specific associations were also identified. CONCLUSIONS: Sexual concerns seem frequent, persistent, and insufficiently addressed. Pretreatment concerns, endocrine therapy, and emotional distress are commonly associated factors. A proactive evaluation of sexual health across the care continuum is needed, to promptly identify patients suitable for multidisciplinary counseling, referral, and supportive interventions.

Factors associated with enrolment in clinical trials among women with early-stage breast cancer.

BACKGROUND: Clinical trials allow development of innovative treatments and ameliorate the quality of clinical care in oncology. Data show that only a minority of patients are enrolled in clinical trials. We assessed enrolment in clinical trials and its correlates among women with early breast cancer. METHODS: We included 9516 patients with stage I-III breast cancer from the multicenter, prospective CANTO study (NCT01993498), followed-up until year 4 (Y4) post-diagnosis. We assessed factors associated with enrolment using multivariable logistic regression. In exploratory, propensity score matched analyses, we used multiple linear regression to evaluate the relationship of enrolment in clinical trials with the European Organisation for Research and Treatment of Cancer Quality Of Life (QoL) questionnaire (EORTC QLQ-C30) Summary Score and described clinical outcomes (distant disease event, invasive disease event, and death by any cause) according to enrolment. RESULTS: Overall, 1716 patients (18%) were enrolled in a clinical trial until Y4 post-diagnosis of breast cancer. Socioeconomic factors were not associated with enrolment. Centres of intermediate volume were most likely to enrol patients in clinical trials [versus low volume, odds ratio 1.45 (95% confidence interval (CI) 1.08-1.95), P = 0.0124]. Among 2118 propensity score matched patients, enrolment was associated with better QoL at Y4 (adjusted mean difference versus not enrolled 1.37, 95% CI 0.03-2.71, P = 0.0458), and clinical outcomes (enrolled versus not enrolled, distant disease event 7.3% versus 10.1%, P = 0.0206; invasive disease event 8.2% versus 10.5%, P = 0.0732; death by any cause 2.8% versus 3.7%, P = 0.2707). CONCLUSIONS: In this large study, one in five patients enrolled on a clinical trial until Y4 after diagnosis of early breast cancer. Geographical and centre-related factors were significantly associated with enrolment in clinical trials. Inclusion in clinical trials seemed associated with improved QoL and clinical outcomes. Access to innovation for early-stage breast cancer patients should be encouraged and facilitated by overcoming organizational and geographical barriers to recruitment.

Prognosis of deep infection in spinal surgery using implants, treated by retention, removal of bone graft and lengthy antibiotherapy. / Pronóstico de la infección profunda en la cirugía raquídea con implante, tratada mediante retención, retirada del injerto óseo y antibioterapia prolongada.

OBJECTIVE: Surgical site infections (SSIs) are complications that predispose to a high risk of unfavourable surgical outcomes. The aim of this study was to assess the SSI rate in this type of patients and their prognosis with similar treatment. MATERIALS AND METHODS: A retrospective case series of 799 patients above 18 years old with spinal instrumentation surgery, between January 2010 and December 2014 in the traumatology and orthopaedic surgery department of our institution. All patients with SSIs were treated by debridement, graft replacement, retention of the instrumentation and lengthy courses of antimicrobial therapy. The patients were followed up for a period of 12 months. RESULTS: Of all the patients with arthrodesis, 32 (4%) had spinal SSIs. Three patients were lost to follow-up. The final sample analyzed comprised 29 cases, with a median age of 54.9 years (IQR, 45.7-67 years) and a Charlson comorbidity index of 2.0 (IQR; 0-3). A microbiological diagnosis was obtained in 75.8% of the cases. Of these, the ISSs were monomicrobial in 68.2% and polymicrobial in 31.8%. Once treatment had been completed, 96% were cured without sequelae, and the rate of recurrence and reoperation was 4%. CONCLUSIONS: Treatment based on debridement, retention of the instrumentation, graft replacement and lengthy courses of antimicrobial therapy seems a very effective strategy in the treatment of patients with deep surgical site infection in spine surgery.

Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

UNICANCER-PEGASE 07 study: a randomized phase III trial evaluating postoperative docetaxel-5FU regimen after neoadjuvant dose-intense chemotherapy for treatment of inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive disease requiring a multimodal treatment. We evaluated the benefit of adding docetaxel-5-fluorouracil (D-5FU) regimen after preoperative dose-intense (DI) epirubicin-cyclophosphamide (EC) and locoregional treatment in IBC patients. PATIENTS AND METHODS: PEGASE 07 was a national randomized phase III open-label study involving 14 hospitals in France. Women with nonmetastatic IBC were eligible and randomly assigned to receive either four cycles of DI EC (E 150 mg/m(2) and C 4000 mg/m(2) every 3 weeks with repeated hematopoietic stem cell support), then mastectomy with axillary lymph node dissection, and radiotherapy (arm A) or the same treatment followed by four cycles of D-5FU (D 85 mg/m(2), day 1 and 5FU 750 mg/m(2)/day continuous infusion, days 1-5 every 3 weeks) administered postradiotherapy (arm B). Patients with hormone receptor-positive tumors received hormonal therapy. Disease-free survival (DFS) was the primary end point. Secondary end points included tolerance, pathological complete response (pCR) rate, and overall survival (OS). RESULTS: Between January 2001 and May 2005, 174 patients were enrolled and treated (87 in each arm). Median follow-up was similar in both arms: 59.6 months [95% confidence interval (CI) 58.4-60.3] in arm A and 60.5 months (95% CI 58.3-61.4) in arm B. The estimated 5-year DFS rates were not different: 55% (95% CI 43.9-64.7) in arm A and 55.5% (95% CI 44.3-65.3) in arm B [hazard ratio (HR) = 0.94 (0.61-1.48); P = 0.81]. Identical results were observed for 5-year OS: 70.2% (95% CI 59.1-78.8) in arm A and 70% (95% CI 58.8-78.7) in arm B [HR = 0.93 (0.55-1.60); P = 0.814]. Following DI EC induction, in-breast and global (breast plus nodes) pCR were 28.9% and 20.1%, respectively. Estrogen receptor and pCR status were independently associated with survival. CONCLUSION: The addition of D-5FU after preoperative DI EC and standard local therapy did not improve DFS in IBC. CLINICAL TRIAL NUMBER: ClinicalTrials.gov identifier: NCT02324088.

Comparison of the prognostic value of genomic grade index, Ki67 expression and mitotic activity index in early node-positive breast cancer patients.

Background The genomic grade index (GGI) completes the prognostic value of histological grade (HG). Other proliferation markers include the mitotic activity index (MAI) and the Ki67 immunohistochemistry (IHC) status. We compared the prognostic value of GGI, HG, MAI, Ki67 IHC and messenger RNA (mRNA) status in node-positive breast cancer (BC) patients treated with adjuvant anthracycline-based chemotherapy in the prospective PACS01 trial. Patients and methods The five proliferation-related parameters (GGI, Ki67 mRNA expression and centrally determined HG, MAI, and Ki67 IHC status) of tumours were available for 204 cases and analysed as continuous values. We compared the correlations of each one with the other proliferation-related parameters and with histoclinical variables including the disease-free survival (DFS). Results Expected correlations were observed between the five parameters and for each parameter with biological features (hormone-receptor and HER2 status, molecular subtypes), but the GGI displayed the strongest correlations. The GGI outperformed the prognostic performance of the four other proliferation-related parameters for the DFS in all 204 patients and in the 95 HG2 patients. In multivariate analysis including the classical prognostic factors, only GGI remained significant. Finally, the GGI outperformed the prognostic performance of MKI67 mRNA expression in a series of 1599 samples and 656 HG2 cases. Conclusions In this small pilot biomarker study ancillary to the PACS01 trial, the GGI outperforms the prognostic performance of centrally determined HG, MAI, Ki67 IHC status and mRNA expression. Further validation is warranted in larger series.

A refined molecular taxonomy of breast cancer.

The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER+/PR+/AR+, one was ER-/PR-/AR+ and one was triple negative (AR-/ER-/PR-). ERBB2-amplified tumors were split between the ER-/PR-/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer.

High rate of extra-haematological toxicity compromises dose-dense sequential adjuvant chemotherapy for breast cancer.

BACKGROUND: A dose-dense strategy has been considered to improve results of adjuvant chemotherapy for breast cancer. This randomised phase II trial investigated the feasibility of this approach with sequential anthracyclines and taxanes-based chemotherapy. METHODS: Patients with high-risk node-positive breast cancer were treated with three cycles of fluorouracil 500 mg m(-2), epirubicin 100 mg m(-2), cyclophosphamide 500 mg m(-2) (FEC 100) followed by three cycles of docetaxel 100 mg m(-2) delivered at 2-weekly intervals supported by primary prophylaxis with filgrastim. All patients were randomised to either uninterrupted treatment (arm A) or to have a 2-week additional period of rest between the FEC and docetaxel (arm B). The primary endpoint was the rate of success of chemotherapy delivery. Using a two-stage Fleming design, 120 patients were required with one interim analysis. RESULTS: In March 2005, enrolment was stopped into arm A after the observation of severe skin toxicities. Following the planned interim analysis, the study was closed because of the high rate of grade 3/4 skin toxicities in both arms (arm A: 32.4% and arm B: 18.9%). CONCLUSION: Sequential dose-dense FEC 100 followed by docetaxel 100 mg m(-2) is not feasible. Feasibility still depends largely on several factors including the choice of drugs, dosage and sequence of administration.

Participants' uptake of clinical trial results: a randomised experiment.

BACKGROUND: Participants are showing great interest these days in obtaining the results of clinical trials. The aim of this study was to assess patients' uptake and understanding of the results of the trial in which they have participated and the impact of a letter offering patients the possibility of consulting the trial results on a specific website. METHODS: Breast cancer patients participating in a trial on the efficacy of Trastuzumab were randomly subdivided into an Internet group (who received the letter of invitation) and a control group (who did not receive it). Among 115 HER2-positive women from 21 centres, 107 (93%) answered a self-administered questionnaire. RESULTS: Most of the patients in both groups had access to the Internet (72.0%). The majority (97.2%) stated that receiving information about the trial results would be useful, and the oncologist was the most frequently preferred information provider. The Internet group's declared uptake of the trial results was only slightly higher (47.1% vs 33.9%; P=0.166); however, they understood the results significantly more accurately (18.8% vs 5.6%; P=0.039). INTERPRETATION: Although Internet was not the respondents' preferred source of information, the possibility of using this source slightly increased the uptake and understanding of the results.

Cost-effectiveness of adjuvant docetaxel for node-positive breast cancer patients: results of the PACS 01 economic study.

BACKGROUND: Using data from the PACS 01 randomized trial, we evaluated the cost-effectiveness of anthracyclines plus docetaxel (Taxotere; FEC-D) versus anthracyclines alone (FEC100) in patients with node-positive breast cancer. PATIENTS AND METHODS: Costs and outcomes were assessed in 1996 patients and the incremental cost-effectiveness ratios (ICERs) were estimated, using quality-adjusted life years (QALYs) as outcome. To deal with uncertainty due to sampling fluctuations, confidence regions around the ICERs were calculated and cost-effectiveness acceptability curves were drawn up. Sensitivity analyses were also carried out to assess the robustness of conclusions. RESULTS: The mean cost of treatment was 33% higher with strategy FEC-D, but this difference decreased to 18% at a 5-year horizon. The ICER of FEC-D versus FEC100 was estimated to be 9665euro per QALY gained (95% confidence interval euro2372-euro55 515). The estimated probability that FEC-D was cost-effective reached >96% for a threshold of euro50 000 per QALY gained. If the price of taxane decreased slightly, the ICER would reach some very reasonable levels and this strategy would therefore be much more cost-effective. CONCLUSION: The sequential use of FEC100 followed by docetaxel appears to be a cost-effective alternative, even when uncertainty is taken into account.

Enlargement of the proximal pituitary stalk associated with spontaneous recovery from multiple pituitary hormone deficiencies.

We report the case of a child with multiple pituitary hormone deficiencies and a truncated pituitary stalk on MR imaging who had recovery of normal secretion of pituitary hormones in early adulthood. Follow-up MR imaging examination after recovery revealed marked enlargement of the proximal pituitary stalk. The case of our patient helps to explain the mechanism whereby some patients experience recovery of hormonal function.

Testicular seminoma in a patient with a constitutively activating mutation of the luteinizing hormone/chorionic gonadotropin receptor.

A white man who had been diagnosed, 35 years previously at the age of 27 months, to have precocious puberty, was later determined to have familial male-limited precocious puberty (FMPP), on the basis of his family history, increased serum testosterone, prepubertal concentrations of follicle stimulating hormone and luteinizing hormone, and Leydig cell hyperplasia. Recently, this diagnosis was confirmed by molecular genetic analysis that demonstrated the presence of a heterozygous constitutive activating mutation of the luteinizing hormone/chorionic gonadotropin receptor. This dominant gain-of-function Asp578Gly mutation has been shown constitutively to activate the receptor in the absence of the agonist, leading to enhanced synthesis of cAMP and, in turn, to increased, sustained production of testosterone. In 1994, this patient was found to have a testicular seminoma. He represents the first case of a testicular germ cell tumor described in an FMPP patient, raising the possibility of a potentially harmful effect of prolonged increased concentrations of sex hormones, with onset early in life, upon the cellular components of the testes.

Clinical utility of plasma membrane vesicles expressing recombinant glycophorin A-encoded blood group antigens.

BACKGROUND: Although the genes encoding most of the major blood group determinants are now cloned, recombinant blood group antigens are not commonly used in the clinical laboratory. This study assessed the feasibility of using plasma membrane vesicles expressing recombinant glycophorin A blood group antigens as soluble immunoadsorbants. STUDY DESIGN AND METHODS: Chinese hamster ovary cells were transfected with plasmids containing the cDNA encoding the M- or N-allele of glycophorin A. Plasma membrane vesicles were chemically induced from stable, high-expressing cell lines. Antibodies were assessed for reactivity in hemagglutination-inhibition assays. RESULTS: Eight anti-M antibodies were evaluated. Vesicles expressing the M-allele of glycophorin A neutralized four antibodies (two murine monoclonals; two human sera), while the activity of four human sera was unaffected. Three anti-N reagents were also evaluated (murine monoclonal antibody; rabbit polyclonal antibody; Vicia graminea lectin). All were neutralized by vesicles expressing the N-allele of glycophorin A. There was no detectable neutralization of other clinically significant blood group antibodies. CONCLUSIONS: Plasma membrane vesicles expressing recombinant glycophorin blood group determinants may prove to be useful reagents in the clinical laboratory. However, the partial failure of M antibody recognition requires further study. This general approach could be utilized for any similarly expressed recombinant blood group antigen.

Enzyme immunoassay for identification of Vibrio vulnificus in seawater, sediment, and oysters.

Historically, methods used to identify Vibrio vulnificus in environmental samples have been inadequate because isolation and identification procedures are time-consuming and fail to separate V. vulnificus from other bacterial species. We describe an enzyme immunoassay (EIA) and culture techniques which identified V. vulnificus in seawater, sediment, and oysters. The EIA used monoclonal antibody FRBT37 to a species-specific epitope of V. vulnificus. No cross-reactions were observed among 72 non-V. vulnificus strains comprising 34 species and 15 genera. In field trials, the EIA identified correctly 99.7% of 348 biochemically confirmed V. vulnificus isolates. The epitope corresponding to FRBT37 was found in cells lysed by Triton X-100, deionized H2O, and ultrasonication but was not found in culture supernatants, indicating that its location was intracellular. In addition, electron micrographs of V. vulnificus labeled with FRBT37-biotin-avidin-gold showed that epitope FRBT37 reacted with fragments of lysed cells but not whole cells. FRBT37 was expressed when V. vulnificus was cultured in different growth media. The minimum level of detection of the EIA was approximately 2,000 V. vulnificus cells per EIA well. Epitope FRBT37 was labile at 70 degrees C for 30 min. Immunoblot and EIA plate formats reduced assay time and facilitated handling large numbers of test samples.

Enzyme linked immunosorbent assay for detecting adenoviruses in stool specimens: comparison with electron microscopy and isolation.

A commercial enzyme linked immunosorbent assay (ELISA) for detection of adenoviruses in stool samples was compared with the use of electron microscopy and isolation in Graham 293 cells. Although specific, the ELISA was less sensitive than both electron microscopy and isolation. The ELISA had an overall sensitivity of 78% and a specificity of 100%. The sensitivity was related to the amount of virus particles present in the stool sample, increasing to 90% with about 10(7) viral particles/ml of stool. The ELISA was easy to perform, requiring no instrumentation, and is a useful first line test for detection of adenoviruses in stool samples, especially in laboratories without access to an electron microscope. Wider use of ELISAs should help in evaluating the role of adenoviruses in viral gastroenteritis.

Different glycosylation of human prolactin in cystic fibrosis patients.

1. The elevated (Cl) of sweat from cystic fibrosis (CF) skin reverted to normal after the skin had been grafted onto immunoincompetent, congenitally athymic mice [N'NIH(S)-NU]. 2. The sweat (Cl) of CF skin grafts unlike that from normal skin did not increase when the host mice were injected with antibodies to human prolactin (hPRL). 3. One explanation for the above observations postulated a structurally modified PRL in CF patients. Circulating PRL in CF appears to contain a larger amount of glycosylated variants than that of healthy individuals.

Reliability of percutaneous needle aspiration biopsy for diagnosis of bronchogenic carcinoma.

Aspiration biopsy is a widely accepted diagnostic modality for intrathoracic lesions. Between August 1978 and July 1980, percutaneous needle aspiration biopsy was utilized as a means to diagnose intrathoracic lesions in 82 patients. Cytologic diagnosis was obtained in 81 of 82 patients, 60 with a diagnosis of malignant lesions and 21 of nonmalignant lesions. Forty-four patients (53.7%) were treated surgically and 38 patients (46.3%) were treated conservatively, including radiotherapy and/or chemotherapy. Of the 44 patients who came to surgery, 35 had a malignant cytologic diagnosis. Surgery was performed in 11 patients with an initial benign cytologic diagnosis--there were 4 benign tumors, 4 inflammatory lesions and 3 false-negative cases. Of the 3 negatives, two patients had been biopsied on a second occasion with a malignant cytologic diagnosis. Of the 38 patients treated conservatively (malignant 27, benign 10, insufficient specimen 1) only one patient initially considered benign was later diagnosed with unresectable malignancy. The full collaboration of the radiologist and cytologist at the time of the biopsy has contributed to 94% sensitivity, 100% specificity, and 100% predictive valve for aspiration biopsy of intrathoracic lesions.