Lymph node involvement in immunohistochemistry-based molecular classifications of breast cancer

Background

Prognosis and treatment options differ for each molecular subtype of breast cancer, but risk of regional lymph node (LN) metastasis for each subtype has not been well studied. Since LN status is the most important predictor for prognosis, the aim of this study is to investigate the propensity for LN metastasis in each of the five breast cancer molecular subtypes.

Methods

Under an institutional review board–approved protocol, we retrospectively reviewed the charts of all pathologically confirmed breast cancer cases from January 2004 to June 2012. Five subtypes were defined as luminal A (hormone receptor positive, Ki-67 low), luminal B (hormone receptor positive, Ki-67 high), luminal human epidermal growth factor receptor 2 (HER2), HER2-enriched (hormone receptor negative), and triple negative (TN).

Results

A total of 375 patients with complete data were classified by subtype: 95 (25.3%) luminal A, 120 (32%) luminal B, 69 (18.4%) luminal HER2, 26 (6.9%) HER2-enriched, and 65 (17.3%) TN. On univariate analysis, age (<50), higher tumor grade, HER2+ status, tumor size, and molecular subtype were significant for LN positivity. Molecular subtype correlated strongly with tumor size (χ²; P = 0.0004); therefore, multivariable logistic regression did not identify molecular subtype as an independent variable to predict LN positivity.

Conclusions

Luminal A tumors have the lowest risk of LN metastasis, whereas luminal HER2 subtype has the highest risk of LN metastasis. Immunohistochemical-based molecular classification can be readily performed and knowledge of the factors that affect LN status may help with treatment decisions.     

Value of the pretreatment albumin to globulin ratio in predicting long-term mortality in breast cancer patients

Background

Prior studies have demonstrated the prognostic value of pretreatment serum albumin in different types of cancer. The aim of this study was to assess the predictive value of the albumin to globulin ratio (AGR) on survival in breast cancer patients.

Methods

This retrospective study used an unselected cohort of 354 breast cancer patients who had documented total protein and albumin levels prior to chemotherapy. Survival status was obtained from our cancer registry. Survival analysis, stratified by AGR tertiles, was used to evaluate the prognostic value of AGR.

Results

Patients in the highest AGR tertiles (AGR > 1.45) had a lower 5-year mortality rate compared with those in the middle (AGR 1.21 to 1.45) and the lowest (AGR < 1.21) tertiles (6% vs 18% and 32%, P < .001). After adjusting for confounding variables, AGR remained a significant predictor of mortality (P < .002). Moreover, after excluding the patients with albumin levels less than 3.6, the AGR remained a significant predictor of survival (P .0018).

Conclusions

Pretreatment AGR is an independent, significant predictor of long-term mortality in breast cancer patients, even in patients with normal albumin levels.     

Does the volume of ductal carcinoma in situ impact the positive margin rate in patients undergoing breast conservation for invasive breast cancer?

Background

We sought to investigate whether the volume of ductal carcinoma in situ (DCIS) impacts margin status in patients undergoing lumpectomy for invasive breast cancer.

Methods

We identified 358 patients with stages I–III invasive breast cancer and associated DCIS who were treated with breast-conserving therapy from 1999 to 2009. Data included patient and tumor characteristics, percentage of DCIS (<25%, 26%–50%, or >50%), and pathologic outcomes. Data were compared using chi-square and Fisher exact tests. A two-tailed P value of <0.05 was considered significant.

Results

The 358 patients had a mean age of 58 ± 13 y; 260 (72%) patients were >50 y. The volume of DCIS in lumpectomy specimens was <25% in 296 (83%) patients, 26%–50% in 29 (8%) patients, and >50% in 33 (9%) patients. Tumors with decreasing DCIS volume were more likely to be estrogen receptor positive (239 [82%] with <25% DCIS, 21 [72%] with 26%–50% DCIS, 22 [67%] with >50% DCIS; P = 0.026). DCIS volume was not significantly associated with patient age, tumor size, grade, and stage, nodal status, progesterone receptor status, or Her2 status (P > 0.05). Overall, 137 (38%) patients had one or more positive margins, including 97 of 296 (33%) with <25% DCIS volume, 17 of 29 (59%) with 26%–50% DCIS volume, and 23 of 33 (70%) with >50% DCIS volume (P < 0.0001).

Conclusions

The volume of DCIS associated with an invasive breast cancer in the final lumpectomy specimen is a strong predictor of positive surgical margins. Future analyses will focus on the ability of core pathology to provide this information for intraoperative surgical decision making.     

Surgical,oncologic, and cosmetic differences between oncoplastic and nononcoplastic breast conserving surgery in breast cancer patients

Background

There is a lack of information regarding the safety, complication rate, and cosmetic outcome of oncoplastic breast conserving surgery. The purpose of this study is to evaluate and compare oncoplastic and nononcoplastic procedures.

Methods

A retrospective review was conducted of patients treated with oncoplastic or nononcoplastic lumpectomies. Immediate and long-term complication rates and cosmetic satisfaction were compared.

Results

Of the 142 surgeries, 58 were oncoplastic lumpectomies (40.8%). Oncoplastic patients were younger than nononcoplastic patients (60.9 vs 65.2 years, P = .043). Immediate complications were similar with the exception of nonhealing wounds (oncoplastic = 8.6% vs nononcoplastic = 1.2%, P = .042). Cosmetic complaints were similar, but fat necrosis was more common in the oncoplastic group (25.9% vs 9.5%, P = .009). Time to radiation and number of future biopsies were similar between the groups.

Conclusion

Oncoplastic lumpectomy is a safe alternative to standard lumpectomy for selected breast cancer patients.     

Regional recurrence in the era of sentinel lymph node biopsy

Background

The incidence of all-location regional recurrence after sentinel lymph node biopsy is not well documented. This study attempts to identify risk factors.

Methods

A prospectively maintained database was queried to identify patients with a regional recurrence of breast cancer after a first operation for invasive unilateral breast cancer. Patients with regional recurrence were compared with those alive and disease free at 5 years.

Results

Twenty-one of 1,060 patients (2%) experienced a regional recurrence. Most patients (95%) underwent sentinel lymph node biopsy as their axillary staging. Those with regional recurrences had larger tumors (P < .001), higher stage disease (P < .001), more estrogen receptor– and triple-negative breast cancers (P < .001), and more positive lymph nodes (P = .007). Mastectomy (P = .001) and receipt of neoadjuvant and/or chemotherapy (P < .001) were more common among those with regional recurrences.

Conclusions

Regional recurrence of breast cancer occurs infrequently. Risk factors include high-risk cancers, higher stage at presentation, nodal involvement, and need for therapies reflecting higher risk biology.     

Aberrant expression of decoy receptor 3 in human breast cancer: relevance to lymphangiogenesis

Background

Decoy receptor 3 (DcR3), a decoy receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily, is overexpressed in some forms of cancer. It was recently reported that DcR3 could protect endothelial cells from apoptosis, implying a potential role in the development of vessels, whereas its role in the lymphangiogenesis remains unclear. In the present study, we studied the DcR3 expression and its relationship with the lymphatic microvessel density (LMVD) to investigate if it played a role in the lymph metastasis of human breast cancer.

Materials and methods

Real-time polymerase chain reaction and immunohistochemistry were performed to measure the messenger RNA and protein expression of DcR3 in the breast cancer tissues, noncancerous counterparts, and axillary lymph node from 63 patients. LMVD in these specimens was assessed by counting the D2-40 labeled–microvessels. Furthermore, the correlations between DcR3 expression and LMVD and other clinicopathologic parameters were analyzed.

Results

DcR3 was overexpressed in the breast cancer tissue of 58 patients (92.1%) and was also expressed in vascular endothelial cells and tumor cells in the lymph nodes. LMVD in cancer tissue and lymph nodes were both positively correlated to the aberrant expression of DcR3.

Conclusions

The relevance between DcR3 overexpression and LMVD revealed the existence of possible links between DcR3 and lymphangiogenesis. Based on these findings, it is important to further explore the regulation of lymphangiogenesis operated by the reverse tumor necrosis factor signaling of DcR3.     

The accuracy of preoperative core biopsy in determining histologic grade, hormone receptors, and human epidermal growth factor receptor 2 status in invasive breast cancer

Background

Proper determination of histologic type and biomarkers in a core biopsy specimen is important before preoperative systemic therapy. The purpose of this study was to determine the accuracy of preoperative core biopsy through comparative analysis of histologic grade (HG), hormone receptors, and human epidermal growth factor receptor 2 (HER-2) status in both the core biopsy and surgical specimens.

Methods

We identified 104 patients with invasive ductal cancer who underwent core biopsy and definitive surgery in our institution. The histologic type, HG, estrogen receptor (ER), progesterone receptor (PR), and HER-2 status were determined in both the core biopsy and surgical specimens by one pathologist.

Results

The mean age of the 104 patients was 50 ± 9.9 years and the mean number of core biopsies was 5.1 ± .9. The concordance rates for histologic type, HG, ER, PR, and HER-2 status were 100%, 80.8%, 99%, 97.1%, and 86.5%, respectively.

Conclusions

Core biopsy can predict histologic type, HG, ER, PR and HER-2 status preoperatively in breast cancer when used properly.     

Therapy choices and quality of life in young breast cancer survivors: a short-term follow-up

Background

Premenopausal women represent approximately 35% of new breast cancer diagnoses. Diagnosis and treatment may lead to substantial disruption in quality of life (QOL).

Methods

Premenopausal patients (aged 18 to 50 years) treated for nonmetastatic breast cancer completed a mailed questionnaire. Multiple self-reported QOL measures and clinical data were collected. Cluster analysis and Cronbach's α were used to validate the survey. Analysis of variance was performed for specific interventions. Lower interference scores conveyed higher QOL.

Results

The response rate was 49.8%. Cronbach's α was 0.96. Immediate contralateral prophylactic mastectomy (CPM) carried the highest interference (mean, 3.3148) with sexuality compared with no CPM (mean, 2.85) or delayed CPM (P = .03). Breast conservation had the least interference with appearance (P < .01) and work and finances (P = .02).

Conclusions

Therapeutic mastectomy and CPM with or without reconstruction may adversely affect QOL. These findings suggest that the choice and timing of interventions may significantly affect patient satisfaction.     

An Open,Randomised, Multicentre,Phase 3 Trial Comparing the Efficacy of Two Tamoxifen Schedules in Preventing Gynaecomastia Induced by Bicalutamide Monotherapy in Prostate Cancer Patients

Background

Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration.

Objective

To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated.

Design, setting, and participants

This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n = 41) and weekly (n = 39). Median follow-up was 24.2 mo.

Intervention

Daily bicalutamide (150 mg) plus daily tamoxifen 20 mg continuously (daily group) or the same but with tamoxifen at 20 mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events.

Measurements

For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires.

Results and limitations

Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p < 0.0001), and it was more severe in patients who switched to weekly tamoxifen (p = 0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p = 0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far.

Conclusions

This study demonstrated that tamoxifen 20 mg/wk is inferior to tamoxifen 20 mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20 mg for the prophylaxis of bicalutamide-induced breast events were confirmed.     

Seven In Absentia Homolog 2 (SIAH2) downregulation is associated with tamoxifen resistance in MCF-7 breast cancer cells

Background

A significant percentage of estrogen receptor (ER)–positive breast cancers are resistant to tamoxifen therapy. Seven in Absentia Homolog 2 (SIAH2), an E3 ubiquitin protein ligase, has been shown to be associated with resistance to antiestrogens. We sought to assess its role in the resistance of a breast cancer cell line, MCF-7, to the ER antagonist, tamoxifen.

Materials and methods

A bioinformatic approach was used for the analysis of SIAH2 expression in breast cancer. MCF-7 and MDA-MB-231, which are ER-positive and -negative breast cancer cell lines, respectively, were used for in vitro studies. SIAH2 and ER-α were selectively knocked down in these cell lines with small-interfering RNAs. Knockdowns were confirmed with Western blot analysis and quantitative real-time polymerase chain reaction. Cells with SIAH2 knockdown were treated with tamoxifen and compared with controls.

Results

Knockdown of SIAH2 followed by treatment with tamoxifen resulted in a significant decrease in the sensitivity of treated ER-positive cells. Of note, knockdown of SIAH2 resulted in downregulation of ER-α, whereas knockdown of ER-α had minimal effect on SIAH2. Consistent with this result, the bioinformatic analysis of clinical data revealed that SIAH2 expression is significantly correlated with ER positivity in human breast cancers, and low SIAH2 expression is associated with a poorer response to tamoxifen.

Conclusions

SIAH2 appears to be an important modulator of tamoxifen sensitivity in ER-positive MCF-7 cells, mediated, at least in part, through regulation of ER-α expression. Low expression of SIAH2 may be one of the mechanisms that contribute to tamoxifen resistance in human breast cancer.     

Safety and Efficacy of the Specific Endothelin-A Receptor Antagonist ZD4054 in Patients with Hormone-Resistant Prostate Cancer and Bone Metastases Who Were Pain Free or Mildly Symptomatic: A Double-Blind,Placebo-Controlled,Randomised, Phase 2 Trial

Background

The endothelin-A receptor (ETAR) has been implicated in the progression of prostate cancer.

Objectives

To investigate the safety and efficacy of the specific ETAR antagonist ZD4054 in patients with metastatic hormone-resistant prostate cancer (HRPC).

Design, setting, and participants

Double-blind, placebo-controlled, randomised, parallel-group, multicentre, phase 2 trial in patients attending cancer centres with HRPC and bone metastases who were pain free or mildly symptomatic for pain.

Intervention

Patients were randomised to receive once-daily oral tablets of ZD4054 10 mg, or ZD4054 15 mg, or placebo.

Measurements

The primary end point was time to progression, defined as clinical progression, requirement for opiate analgesia, objective progression of soft-tissue metastases, or death in the absence of progression. Secondary end points included overall survival, time to prostate-specific antigen (PSA) progression, and safety. Statistical significance was preset at 20%.

Results and limitations

A total of 312 patients were randomised (ZD4054 10 mg, n = 107; ZD4054 15 mg, n = 98; placebo, n = 107). At the primary analysis, median time to progression was 3.6 mo, 4.0 mo, and 3.8 mo in the placebo, ZD4054 10 mg, and ZD4054 15 mg groups, respectively, with no statistically significant difference between ZD4054 groups and placebo (hazard ratio [HR] vs placebo for the ZD4054 10 mg group: 0.88 [80% CI: 0.71–1.09]; HR vs placebo for the ZD4054 15 mg group: 0.83 [80% CI: 0.66–1.03]). However, a signal for prolonged overall survival was observed in the ZD4054 treatment groups versus placebo, based on 40 deaths. At a subsequent analysis after 118 deaths, this survival benefit was confirmed (HR vs placebo for the ZD4054 10 mg group, 0.55 [80% CI: 0.41–0.73], p = 0.008; HR vs placebo for the ZD4054 15 mg group, 0.65 [80% CI: 0.49–0.86], p = 0.052) but the differences in time to progression remained nonsignificant. Median overall survival was 17.3 mo, 24.5 mo, and 23.5 mo in the placebo group, the ZD4054 10 mg group, and the ZD4054 15 mg group, respectively. Discordance between results for time to progression and overall survival may be due to the sensitivity of the definition of progression. Adverse events were in line with the expected pharmacologic effects of an ETAR antagonist.

Conclusions

The primary end point of time to progression was not achieved in this study, but an improvement was seen in overall survival in both active treatment arms. ZD4054 was well tolerated.

Trial registration

Clinicaltrials.gov NCT00090363.     

Is chronic kidney disease an independent risk factor for mortality in breast cancer?

Background

Chronic kidney disease (CKD) is an independent risk factor for morbidity and mortality in multiple disease processes. However, not much is known about the relationship between breast cancer and CKD. CKD is associated with increased difficulty in breast cancer screening or surveillance due to increased calcifications on mammography. In addition, there is concern regarding the optimization of serum levels of chemotherapeutics in patients with CKD or on hemodialysis. We hypothesized that CKD is an independent risk factor for mortality in patients with breast cancer.

Methods

A case-matched, retrospective review of a prospectively maintained database was conducted on patients treated for breast cancer at an academic medical center between 1998 and 2011. Glomerular filtration rates (GFRs) were calculated for each patient at the time of diagnosis, and patients with CKD (GFR <60 mL/min) were matched in a 1:2 ratio with patients with GFR >60 mL/min, controlling for age, stage at diagnosis, and race. Primary end points measured were disease-free survival and overall survival. Statistical analysis was performed using Student t-test and Kaplan–Meier.

Results

Of the 1223 total patients, 54 (4%) had CKD. One hundred five patients without CKD were matched for age, stage at diagnosis, and race. Mean GFR among patients with and without CKD were 47.6 and 83.2 mL/min, respectively (P < 0.001). The 5-y overall survival was 77% for patients with CKD and 86% for patients without CKD (P = 0.47). Disease-free survival was 64% and 81%, respectively (P = 0.45).

Conclusion

Based on our data, CKD does not appear to have a significant impact on outcomes in patients with breast cancer.     

Survival Following Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiotherapy in Patients With Prostate Cancer: The Impact of Competing Causes of Mortality and Patient Stratification

Background

Data regarding the natural history of biochemical recurrence (BCR) after radical prostatectomy (RP) and adjuvant radiotherapy (aRT) are limited.

Objective

To evaluate cancer-specific (CSM) and other-cause mortality (OCM) in prostate cancer patients with BCR after RP and aRT.

Design, setting, and participants

We identified 336 patients with BCR treated between 1990 and 2006 at two tertiary care centers.

Intervention

All patients underwent RP plus aRT.

Outcome measurements and statistical analysis

Cox regression analyses were used to evaluate the association between clinicopathologic variables and CSM. The coefficients of CSM-independent predictors were used to develop a novel nomogram. Patients were stratified into groups according to nomogram-calculated CSM probability and median age. Competing-risks survival analyses were used to estimate CSM and OCM for each group.

Results and limitations

Ten-year CSM and OCM were 21.5 and 21.7%, respectively. On multivariable analyses, short time to BCR, pathologic Gleason score ≥8, and positive lymph node count of more than two at RP were significantly associated with increased CSM rate (all p ≤ 0.01). These variables were used to develop a novel nomogram, which was used to stratify patients according to their 10-yr, nomogram-calculated, CSM probability: ≤10% versus >10–30% versus >30%. On competing-risks analysis, 10-yr CSM rate for these groups was 6%, 15%, and 42%, respectively, for patients aged ≤68 yr, versus 8%, 19%, and 42% for patients aged >68 yr. Likewise, 10-yr OCM rate was 24%, 9%, and 10%, respectively, for patients aged ≤68 yr, versus 37%, 20%, and 28%, respectively, for patients aged >68 yr. The study is limited by its retrospective design.

Conclusions

Short time to BCR, pathologic Gleason score ≥8, and more than two positive lymph nodes were independent predictors of CSM in patients with BCR after RP and aRT. Men with these features may benefit from additional secondary therapies, ideally, in a clinical trial setting.     

Predicting Survival of Patients with Node-positive Prostate Cancer Following Multimodal Treatment

Background

According to the TNM staging system, patients with prostate cancer (PCa) with lymph node invasion (LNI) are considered a single-risk group. However, not all LNI patients share the same cancer control outcomes.

Objective

To develop and internally validate novel nomograms predicting cancer-specific mortality (CSM)–free rate in pN1 patients.

Design, setting, and participants

We evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant therapy at two tertiary care centers between 1988 and 2010.

Outcome measurements and statistical analysis

Univariable and multivariable Cox regression models tested the relationship between CSM and patient clinical and pathologic characteristics, which consisted of prostate-specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage, status of surgical margins, number of positive lymph nodes, and status of adjuvant therapy. A Cox regression coefficient-based nomogram was developed and internally validated.

Results and limitations

All 1107 patients received adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87% in patients treated with aRT plus aHT versus 82% in patients treated with aHT alone (p = 0.08). At multivariable analyses, PSA value, pathologic Gleason score, pathologic tumor stage, surgical margin status, number of positive lymph nodes, and aRT status were statistically significant predictors of CSM (all p ≤ 0.04). Based on these predictors, nomograms were developed to predict the 10-yr CSM-free rate in the overall patient population and in men with biochemical recurrence. These models showed high discrimination accuracy (79.5–83.3%) and favorable calibration characteristics. These results are limited by their retrospective nature.

Conclusions

Some patients with pN1 PCa have favorable CSM-free rates at 10 yr. We developed and internally validated the first nomograms that allow an accurate prediction of the CSM-free rate in these patients at an individual level.     

Evaluation of Functional Status,Pulmonary Capacity,Body Composition,and Quality of Life of End-Stage Liver Disease Patients Who are Candidates for Liver Surgery

Introduction

Muscular weakness in combination with malnutrition can induce a global motor impairment and physical inactivity, adversely impairing the daily living activities and quality of life of end-stage liver disease patients who are candidates for liver transplantation.

Objectives

To evaluate functional status, pulmonary capacity, body composition and quality of life in end-stage liver disease patients who are candidates for liver transplantation; to verify if there is a correlation between the functional variables of the individuals tested through the 6-minute walk test (6MWT) and covariables: pulmonary function test (PFP), quality of life and body composition.

Methods

This study was carried out at the Liver Transplantation Unit of the State University of Campinas (UNICAMP). We included 46 patients with end-stage liver disease who underwent the following evaluations: medical history, quality of life questionnaire “Short Form 36” (SF-36), surface electromyography (sEMG) of the diaphragm and rectus abdominis muscles, body composition assessment by electrical vioimpedance (BIA), 6MWT and PFP.

Results

Univariate analysis and Pearson's correlation found correlations between distance walked on 6MWT and QOL (P = .006 and P = .02) and TBW (P = .5 and P = .02). Pearson's correlation were found between respiratory variables of 6MWT, QOL, and PFP.

Conclusion

The functional status may be correlated to body composition, quality of life and pulmonary capacity of patients with liver disease, candidates for transplantation.     

Additional Analysis of the Secondary End Point of Biochemical Recurrence Rate in a Phase 3 Trial (CS21) Comparing Degarelix 80 mg Versus Leuprolide in Prostate Cancer Patients Segmented by Baseline Characteristics

Background

Recent data suggest prostate-specific antigen (PSA) progression may predict overall survival in prostate cancer patients.

Objective

To compare the activity of degarelix and leuprolide regarding PSA recurrence-free survival.

Design, setting, and participants

Phase 3, 1-yr, multicentre, randomised, open-label trial comparing the efficacy and safety of degarelix at 240 mg for 1 mo, and then 80 mg monthly (240/80 mg); degarelix at 240 mg for 1 mo, and then 160 mg monthly; and leuprolide at 7.5 mg/mo. Overall, 610 patients with histologically confirmed prostate cancer (all stages), for whom androgen deprivation therapy was indicated, were included. The primary end point of this trial has been reported previously; the protocolled and exploratory subgroup analyses reported in this paper focus on degarelix at 240/80 mg (dose approved by the US Food and Drug Administration and the European Medicine Evaluation Association for the treatment of patients with hormone-naive advanced prostate cancer).

Measurements

PSA progression-free survival (two consecutive increases in PSA of 50% compared with nadir and ≥5 ng/ml on two consecutive measurements at least 2 wk apart or death) and change in PSA were reviewed. Effects of baseline disease stage (localised, locally advanced, and metastatic) and PSA level (<10, 10–20, >20–50, and >50 ng/ml) were analysed.

Results and limitations

Patients receiving degarelix showed a significantly lower risk of PSA progression or death compared with leuprolide (p = 0.05). PSA recurrences occurred mainly in patients with advanced disease and exclusively in those with baseline PSA >20 ng/ml. Patients with PSA >20 ng/ml had a significantly longer time to PSA recurrence with degarelix (p = 0.04). The relatively low number of patients in each subgroup is a limitation of this study.

Conclusions

These results generate the hypothesis that degarelix at 240/80 mg offers improved PSA control compared with leuprolide. PSA recurrences occurred almost exclusively in patients with metastatic prostate cancer or high baseline PSA during this 1-yr study. Further studies are warranted to confirm these findings.     

Validation and Reliability Testing of the EORTC QLQ-NMIBC24 Questionnaire Module to Assess Patient-reported Outcomes in Non–Muscle-invasive Bladder Cancer

Background

Well-developed and well-tested patient-reported outcome measures for non–muscle-invasive bladder cancer (NMIBC) are required.

Objective

To test and adapt the scale structure and explore the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire for NMIBC.

Design, setting, and participants

A total of 433 patients in the Bladder COX-2 Inhibition Trial (BOXIT) completed the EORTC QLQ-C30 and NMIBC questionnaires. BOXIT is evaluating the addition of celecoxib to standard treatment in high- and intermediate-risk NMIBC.

Outcome measurements and statistical analysis

Multitrait scaling investigated and adapted the questionnaire scale structure and evaluated the reliability and validity of the revised scales, as well as responsiveness to change.

Results and limitations

A total of 410 patients (94.7%) (79.3% men, 74.6% high risk) returned baseline forms, and the questionnaire response rate was 88.2%. Multitrait scaling confirmed six scales and five single items. Scales and items demonstrated significant differences between patients with good and poor performance status scores (p < 0.001). Men reported better sexual function than women (p < 0.001). Scale and single-item module scores were not highly correlated with QLQ-C30 scores (evidence of discriminant validity), and the module was responsive to changes in health over time. International and test–retest data are required.

Conclusions

This study demonstrates the evidence-driven adapted scale structure and psychometric data of the EORTC QLQ-NMIBC24 module to use in clinical trials of patients with high- or intermediate-risk bladder cancer.     

High TFAP2C/low CD44 expression is associated with an increased rate of pathologic complete response following neoadjuvant chemotherapy in breast cancer

Background

In luminal breast cancer cell lines, TFAP2C regulates expression of key genes in the estrogen receptor–associated cluster and represses basal-associated genes including CD44. We examined the effect of TFAP2C overexpression in a basal cell line and characterized the expression of TFAP2C and CD44 in breast cancer specimens to determine if expression was associated with clinical response.

Methods

MDA-MB-231 breast cancer cells were treated with a TFAP2C-containing plasmid and evaluated for effects on CD44 expression. Pretreatment biopsy cores from patients receiving neoadjuvant chemotherapy for breast cancer were evaluated for TFAP2A, p53, TFAP2C, and CD44 expression by immunohistochemistry.

Results

Overexpression of TFAP2C in MDA-MB-231 cells resulted in decreased expression of CD44 mRNA and protein, P < 0.05. A pathologic complete response (pCR) following neoadjuvant chemotherapy was achieved in 17% of patients (4/23). Average expression for TFAP2C by immunohistochemistry in patients with a pCR was 93%, compared with 46% in patients with residual disease, P = 0.016; and in tumors that stained at ≥80% for TFAP2C, 4 of 9 (44%) achieved pCR, compared with 0 of 14 below 80%, P = 0.01. Additionally, in tumors that stained ≤80% for CD44, 4 of 10 (40%) achieved pCR, compared with 0 of 13 >80%, P = 0.02. In tumors that stained high for TFAP2C (≥80%) and low for CD44 (≤80%), 4 of 7 (57%) achieved pCR, compared with 0 of 16 in all other groups (P = 0.004).

Conclusions

TFAP2C repressed CD44 expression in basal-derived breast cancer. In primary breast cancer specimens, high TFAP2C and low CD44 expression were associated with pCR after neoadjuvant chemotherapy and could be predictive of tumors that have improved response to neoadjuvant chemotherapy.     

A new risk classification rule for curve progression in adolescent idiopathic scoliosis

Background context

Prognostic factors for curve progression of adolescent idiopathic scoliosis (AIS) have been reported previously. There is only one existing rule that classifies AIS patients into two groups by a curvature of 25°.

Purpose

This study aimed to develop a more refined risk classification rule for AIS.

Study design

This was a retrospective cohort study.

Patient sample

We examined 2,308 untreated AIS patients, aged 10 years and older, who had a Risser sign of 2 and lesser and a curvature less than 30° at presentation.

Outcome measures

Outcome was taken as the time to progression to 30°.

Methods

Patients' clinical parameters were analyzed by Classification and Regression Tree analysis.

Results

The new classification rule identified four risk groups of curve progression. Patients with a curvature of 26° and more and less than 18° constituted the highest and lowest risk groups, respectively. The two intermediate groups were identified by the age (11.3 years), menarcheal status, and body height (154 cm).

Conclusions

The risk classification rule only uses information at the first presentation and can aid physicians in deriving an efficient management.     

Infiltration de ropivacaïne en chirurgie carcinologique du sein : effet sur la douleur postopératoire aiguë et chronique

Objectives

Decrease acute pain after breast cancer surgery by an infiltration of ropivacaine. Analyse effect on chronic pain.

Study design

Prospective randomised double blind versus placebo study.

Patients and methods

Eighty-one patients randomised between two groups received wound infiltration with 40 ml of ropivacaine 4.75 mg/ml or placebo. Acute pain was assessed during 24 h with analogical visual scale and antalgic consumption. One year later, telephonic interviews looked for chronic pain and evaluate it with McGill Pain Questionnaire.

Results

Analogical visual scale pain score, antalgic consumption and chronic pain incidence were similar between groups.

Conclusion

Ropivacaine scar infiltration provided no acute or chronic pain relief after breast cancer surgery.