An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients: EORTC QLQ-BR45.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 was one of the first disease-specific questionnaires developed in 1996 to assess quality of life (QoL) in patients with breast cancer (BC). However, since 1996 major changes in BC treatment have occurred, requiring an update of the EORTC BC module. This study presents the results of the phase I-III update of the QLQ-BR23 questionnaire. PATIENTS AND METHODS: The update of the EORTC QLQ-BR23 module followed standard EORTC guidelines. A systematic literature review revealed 83 potential relevant QoL issues during phases I and II. After shortening the issues list and following interviews with patients and health care providers, 15 relevant issues were transformed into 27 items. The preliminary module was pretested in an international, multicentre phase III study to identify and solve potential problems with wording comprehensibility and acceptability of the items. Descriptive statistics are provided. Analyses were qualitative and quantitative. We provide a psychometric structure of the items. RESULTS: The phase I and II results indicated the need to supplement the original QLQ-BR23 with additional items related to newer therapeutic options. The phase III study recruited a total of 250 patients (from 12 countries). The final updated phase III module contains a total of 45 items: 23 items from the QLQ-BR23 and 22 new items. The new items contain two multi-item scales: a target symptom scale and a satisfaction scale. The target symptom scale can be divided into three subscales: endocrine therapy, endocrine sexual and skin/mucosa scale. CONCLUSION: Our work has led to the development of a new EORTC QLQ-BR45 module that provides a more accurate and comprehensive assessment of the impact of new and scalable treatments on patients' QoL. The final version of the EORTC QLQ-BR45 is currently available for use in clinical practice. The final phase IV study is underway to confirm psychometric properties of the module.

Primary surgery versus no surgery in synchronous metastatic breast cancer: patient-reported quality-of-life outcomes of the prospective randomized multicenter ABCSG-28 Posytive Trial.

BACKGROUND: The ABCSG-28 trial compared primary surgery followed by systemic therapy versus primary systemic therapy without surgery in patients with de novo stage IV BC. The present report describes QoL results of this trial. METHODS: Ninety patients with primary operable MBC were randomised to surgery of the primary tumor followed by systemic therapy or to primary systemic therapy without surgery. QoL analyses covering the results at baseline, 6,12,18 and 24 months follow up of 79 (88%) patients, was assessed with the EORTC QLQ-C30 and QLQ-BR23 questionnaires. RESULTS: There were no statistically significant differences in any of the scales of the QLQ-C30 and QLQ-BR23 questionnaires between the two groups over the time. Baseline global health status and physical functioning were predictors for OS (patients with a higher score lived longer (p=0.0250, p=0.0225; p=0.0355, p=0.0355)). Global health status, social functioning scale, breast symptoms and future perspective were predictors for longer TTPd (p=0.0244; p=0.0140, p=0.020; p=0.0438, p=0.0123). Patients in both arms reported significant improvement on the emotional functioning scale. Cognitive functioning decreased over time in both groups. Younger women had clinically relevant better physical and sexual functioning scores (p=0.039 and 0.024). CONCLUSION: Primary surgery does not improve nor alter QoL of patients with de novo stage IV BC. Global health status and physical functioning were predictors for OS and could be use as additional marker for prediction of OS and TTTd in patients with de novo stage IV BC. TRIAL REGISTRATION: The trial is registered on clinicaltrial.gov (NCT01015625, date of registration:18/11/2009).

The impact of distinct triple-negative breast cancer subtypes on misdiagnosis and diagnostic delay.

BACKGROUND: Triple-negative breast cancer (TNBC) includes mostly aggressive types of breast cancer with poor prognosis. Due to its growth pattern, misinterpretation in clinical imaging is more frequent than in non-TNBC. As the group of TNBC contains heterogeneous types of tumors, marker expression-based subtypes have recently been established. We analyzed clinical features and false-negative imaging findings that could potentially lead to diagnostic delay within the subtypes. METHODS: An exploratory analysis compared the imaging features across the a priori defined subtypes and related these findings to molecular subtype, disease stage, potential diagnostic delay, and patient outcome. RESULTS: TNBC cases were categorized into basal-like (BL; 38.6%), mesenchymal-like (ML; 19.9%), luminal androgen receptor (LAR; 28.3%), and immunomodulatory (IM; 13.3%) subtype. In almost every third patient, malignant classification was missed in at least one imaging method. Misclassification in mammogram was more frequent in ML, while benign ultrasound features were reported more often in the BL subtype. Diagnostic delay due to misclassification in imaging led to tumor growth and/or upgrading of the tumor stage in 8.9% of BL tumors, which had the lowest overall survivals. Despite misclassification rate was higher in the ML subtype it showed better outcomes. Misdiagnosis of axillary lymph node metastasis was higher in LAR; however, this subtype showed a higher percentage of affected axillary lymph nodes. CONCLUSION: TNBC subtypes have different clinical features, benign appearances, and diagnostic delay, which can lead to tumor stage upgrade. Future clinical studies on TNBC outcomes might consider the confounder of clinical delay in the subtypes.

International validation of the European Organisation for Research and Treatment of Cancer QLQ-BRECON23 quality-of-life questionnaire for women undergoing breast reconstruction.

BACKGROUND: The aim was to carry out phase 4 international field-testing of the European Organisation for Research and Treatment of Cancer (EORTC) breast reconstruction (BRECON) module. The primary objective was finalization of its scale structure. Secondary objectives were evaluation of its reliability, validity, responsiveness, acceptability and interpretability in patients with breast cancer undergoing mastectomy and reconstruction. METHODS: The EORTC module development guidelines were followed. Patients were recruited from 28 centres in seven countries. A prospective cohort completed the QLQ-BRECON15 before mastectomy and the QLQ-BRECON24 at 4-8 months after reconstruction. The cross-sectional cohort completed the QLQ-BRECON24 at 1-5 years after reconstruction, and repeated this 2-8 weeks later (test-retest reliability). All participants completed debriefing questionnaires. RESULTS: A total of 438 patients were recruited, 234 in the prospective cohort and 204 in the cross-sectional cohort. A total of 414 reconstructions were immediate, with a comparable number of implants (176) and donor-site flaps (166). Control groups comprised patients who underwent two-stage implant procedures (72, 75 per cent) or delayed reconstruction (24, 25 per cent). Psychometric scale validity was supported by moderate to high item-own scale and item-total correlations (over 0·5). Questionnaire validity was confirmed by good scale-to-sample targeting, and computable scale scores exceeding 50 per cent, except nipple cosmesis (over 40 per cent). In known-group comparisons, QLQ-BRECON24 scales and items differentiated between patient groups defined by clinical criteria, such as type and timing of reconstruction, postmastectomy radiotherapy and surgical complications, with moderate effect sizes. Prospectively, sexuality and surgical side-effects scales showed significant responsiveness over time (P < 0·001). Scale reliability was supported by high Cronbach's α coefficients (over 0·7) and test-retest (intraclass correlation more than 0·8). One item (finding a well fitting bra) was excluded based on high floor/ceiling effects, poor test-retest and weak correlations in factor analysis (below 0·3), thus generating the QLQ-BRECON23 questionnaire. CONCLUSION: The QLQ-BRECON23 is an internationally validated tool to be used alongside the EORTC QLQ-C30 (cancer) and QLQ-BR23 (breast cancer) questionnaires for evaluating quality of life and satisfaction after breast reconstruction.

Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12.

BACKGROUND: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. PATIENTS AND METHODS: Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points. RESULTS: After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. CONCLUSION: These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. CLINICALTRIALSGOV: NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

Vaginal prolapse surgery with transvaginal mesh: results of the Austrian registry.

INTRODUCTION AND HYPOTHESIS: Several mesh repair systems for pelvic organ prolapse (POP) were introduced into clinical practice with limited data on safety, complications or success rates, and impact on sexual function. The Austrian Urogynecology Working Group initiated a registry to assess the use of transvaginal mesh devices for POP repair. We looked at perioperative data, as well as outcomes at 3 and 12 months. METHODS: Between 2006 and 2010 a total of 20 gynecology departments in Austria participated in the Transvaginal Mesh Registry. Case report forms were completed to gather data on operations, the postoperative course, and results at 3 and 12 months. RESULTS: A total of 726 transvaginal procedures with 10 different transvaginal kits were registered. Intra- and perioperative complications were reported in 6.8%. The most common complication was increased intraoperative bleeding (2.2%). Bladder and bowel perforation occurred in 6 (0.8%) and 2 (0.3%) cases. Mesh exposure was seen in 11% at 3 and in 12% at 12 months. 24 (10%) previously asymptomatic patients developed bowel symptoms by 1 year. De novo bladder symptoms were reported in 39 (10%) at 3 and in 26 (11%) at 12 months. Dyspareunia was reported by 7% and 10% of 265 and 181 sexually active patients at 3 and 12 months postoperatively respectively. CONCLUSIONS: The 6.8% rate of intra- and perioperative complications is in line with previous reports. Visceral injury was rare. The 12% rate of mesh exposure is consistent with previous series.

Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE).

BACKGROUND: The GENEVIEVE study, comparing neoadjuvant cabazitaxel versus paclitaxel in triple-negative breast cancer (TNBC) and luminal B/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC), previously reported significant differences in pathological complete response (pCR) rates. Effects on long-term outcome are unknown. PATIENTS AND METHODS: GENEVIEVE randomized patients with cT2-3, any cN or cT1, cN+/pNSLN+, centrally confirmed TNBC or luminal B/HER2-negative BC (latter defined as estrogen/progesterone receptor-positive and >14% Ki-67-stained cells) to receive either cabazitaxel 25 mg/m2 q3w for four cycles or paclitaxel 80 mg/m2 weekly for 12 weeks. Anthracycline-containing chemotherapy was allowed in case of histologically proven invasive residuals as neoadjuvant treatment or after surgery as adjuvant treatment. Here we report the secondary endpoints invasive disease-free survival (iDFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: Of the 333 patients randomized, 74.7% and 83.2% completed treatment in the cabazitaxel and paclitaxel arms, respectively. After a median follow-up of 89.3 months (interquartile range 68.8-97.3 months), 80 iDFS events (43 after cabazitaxel and 37 after paclitaxel) and 47 deaths (23 after cabazitaxel and 24 after paclitaxel) were reported. IDFS rates were not significantly different between the cabazitaxel and paclitaxel arms after a 3-year (83.6% versus 85.0%) and 5-year follow-up (76.2% versus 78.3%) [hazard ratio (HR) = 1.27, 95% confidence interval 0.82-1.96, P = 0.294], respectively. DDFS rates at 3 years (88.6% versus 87.8%) and 5 years (82.1% versus 82.8%) for cabazitaxel and paclitaxel were comparable (HR = 1.15, P = 0.573). Similarly, OS rates at 3 years (91.6% versus 91.8%) and 5 years (89.2% versus 86.8%) showed no significant differences (HR = 1.05, P = 0.872). Subgroup analysis for TNBC and luminal B/HER2-negative BCs indicated no significant variations in 3- or 5-year iDFS, DDFS, or OS. CONCLUSIONS: The significant differences in pCR rates observed in both treatment arms did not significantly impact long-term outcomes for patients treated with cabazitaxel versus paclitaxel in the GENEVIEVE trial.

Breast-conserving surgery with intraoperative radiotherapy in recurrent breast cancer: the patient's perspective.

PURPOSE: When ipsilateral breast-tumor recurrence (IBTR) following breast-conserving surgery (BCS) occurs, the cure of a potentially life-threatening disease is the main goal. If, however, this is diagnosed early, prognosis is still good and patient-reported outcomes become more important. Despite the fact that many patients would prefer a further BCS, international breast cancer guidelines still recommend mastectomy, mainly because previous radiation implies limited options. Our comparative study evaluates the long-term quality-of-life and outcome in patients with IBTR who received BCS plus intraoperative radiotherapy (IORT) versus mastectomy. METHODS: Patients with IBTR were retrospectively divided into three groups according to the local treatment: group 1 (n = 26) was treated with BCS + IORT; group 2 (n = 35) received a standard mastectomy; group 3 (n = 52) had a mastectomy with subsequent reconstruction. Outcomes were analyzed after a mean follow-up of 5 years after IBTR. Quality-of-life was evaluated by the validated questionnaire BREAST-Q in 50 patients who fulfilled the inclusion criteria. RESULTS: Quality-of-life scores varied within the groups, ranging from 51.4 to 91.3 (out of 100 points). We observed satisfactory scores in all items, with no statistical difference within the groups. Disease-free survival of all groups did not statistically differ, and overall mortality was very low (0.9%). The postinterventional complication rate was lower after BCS (19.2% versus 34.3% after mastectomy and 30.8% after mastectomy with reconstruction). CONCLUSION: For patients with previous surgery and radiation who demand a second BCS in the recurrent situation, this surgical technique can be offered in combination with IORT. Our long-term results imply oncological safety, lower complication rate, and good patient satisfaction.

Can routine gynecologic examination contribute to the diagnosis of cervical involvement by primary endometrial cancer?

OBJECTIVE: There are few data in the literature as to whether findings at routine preoperative gynecologic examination of patients with primary endometrial cancer including cervical cytology, colposcopy and rectovaginal bimanual pelvic exam could predict cervical extension of the disease. METHODS AND MATERIALS: The present retrospective study was undertaken to preoperatively identify potential clinical parameters associated with the histological diagnosis of cervical involvement by primary endometrial cancer in the hysterectomy specimen. We reviewed the records of 104 patients with Stage II endometrial cancer treated at our institution between 1985 and 2005 by simple or radical abdominal hysterectomy with special emphasis on cervical Pap smear, colposcopy, cervical palpation as well as rectal parametrial assessment. Patients with Stage I disease operated on before and after each study patient were selected as controls (n = 208). Patients with more advanced disease were excluded. RESULTS: Overall, 312 records of patients with primary endometrial cancer were reviewed. Patients with Stage II disease had a significantly lower prevalence (p < 0.0001) of endometrioid carcinomas and a significantly higher (p < 0.01) prevalence of G3 tumors compared to the control patients. Pap smears and colposcopic findings were abnormal in 39% of patients with Stage II and in 9% and 10% of patients with Stage I disease (p < 0.0001). Of patients with Stage II disease, 42% had a suspicious cervical palpation compared to only 4% of patients with Stage I disease (p < 0.0005). Parametrial assessment was suspicious in 16% of patients with Stage II disease and in no patient with Stage I disease (p < 0.001). CONCLUSION: The four routine clinical parameters Pap smear, colposcopy, cervical palpation and rectal parametrial examination are significantly more often pathologic in patients with Stage II than in Stage I disease. The majority of patients with Stage II disease had at least one of these tests positive. Thus they may be useful to preoperatively detect cervical involvement by primary endometrial cancer.

Prognostic impact of PIK3CA protein expression in triple negative breast cancer and its subtypes.

BACKGROUND: Triple negative breast cancer (TNBC) harbors a heterogeneous group of carcinomas with poor prognosis and high genetic variability. As a potential aim for targeted therapy, genetic mutations leading to an activation of the phosphoinositide 3-kinase pathway in a catalytic subunit (PIK3CA) in breast cancer have been analyzed currently. Little is known about the clinical impact and prognostic or predictive value of this marker in TNBC subtypes. METHODS: Samples from 119 TNBC cases were submitted to immunohistochemical PIK3CA protein expression analysis and scored semi-quantitatively as negative, weak (1 +), or strongly expressed (2 +). Expression scores were correlated to patient's characteristics, imaging features, and TNBC subtypes. TNBC subtypes were categorized into four subtypes: basal like, mesenchymal like, luminal androgen receptor (LAR), and immunomodulatory. RESULTS: We did not observe differences in clinical aspects and imaging features between TNBC with and without PIK3CA expression. PIK3CA expression was in general higher in the LAR subtype. The disease-free survival and overall survival were significantly better in TNBC with PIK3CA protein expression, independent of TNBC subtypes. CONCLUSION: Despite conflicting results in the literature, our study clearly shows a better outcome of PIK3CA-expressing TNBC, independent of TNBC subtypes. PIK3CA expression in TNBC is not associated with specific clinical or diagnostic features. Further molecular studies and meta-analysis are warranted to clarify the prognostic and predictive role of PIK3CA protein expression.

Long-term control of bone marrow carcinosis and severe thrombocytopenia with standard-dose chemotherapy in a breast cancer patient: a case report.

BACKGROUND: Primary metastatic breast cancer with bone marrow involvement and pronounced thrombocytopenia is rare. The myelosuppressive effect of most cytotoxic drugs limits chemotherapy in patients with cytopenia due to marrow involvement. CASE REPORT: A 62-year-old patient, who presented with locally and systemically advanced breast cancer, is reported. The initial work-up revealed bone marrow carcinosis with thrombocytopenia of less than 20,000/mm3 lung and osseous metastases without signs of suppressed erythropoiesis and leucopoiesis. The patient was stabilized with 6 different standard-dose chemotherapy regimens, antihormonal therapy, and trastuzumab before dying 57 months after first diagnosis. The patient received only platelet transfusions on 2 instances with platelets of 2,000/mm3. CONCLUSION: This case illustrates that aggressive standard chemotherapy may be feasible in selected patients with bone marrow carcinosis-associated thrombocytopenia without major bleeding episodes.

[Transobturator tapes: better than TVT?]. / Transobturatorische Bänder: Besser als TVT?

Suburethral slings (or tapes) placed by a transobturator approach may be an alternative to established retropubic tension-free vaginal tapes. Comparisons are hampered by the number of available systems. Injury of the bladder, bowel and major vessels appears less frequent with transobturator systems whereas vaginal tape erosion and infectious complications appear to be more common. Results of adequately powered randomized trials are not yet available.

Mesh versus acellular dermal matrix in immediate implant-based breast reconstruction - A prospective randomized trial.

BACKGROUND: Comparative studies on the use of meshes and acellular dermal matrices (ADM) in implant-based breast reconstruction (IBBR) have not yet been performed. METHODS: This prospective, randomized, controlled, multicenter pilot study was performed at four Austrian breast cancer centers. Fifty patients with oncologic or prophylactic indication for mastectomy and IBBR were randomized to immediate IBBR with either an ADM (Protexa(®)) or a titanized mesh (TiLOOP(®) Bra). Complications, failed reconstruction, cosmetic outcome, patients' quality of life and the thickness of the overlying tissue were recorded immediately postoperatively and 3 and 6 months after surgery. RESULTS: 48 patients participated in the study (Protexa(®) group: 23; TiLOOP(®) Bra group: 25 patients). The overall complication rate was 31.25% with similar rates in both groups (Protexa(®) group: 9 versus TiLOOP(®) Bra group: 6; p = 0.188). There was a higher incidence of severe complications leading to failed reconstructions with implant loss in the Protexa(®) group than in the TiLOOP(®) Bra group (7 versus 2; p < 0.0001). An inverted T-incision technique led to significantly more complications and reconstructive failure with Protexa(®) (p = 0.037, p = 0.012, respectively). There were no significant differences in patients' satisfaction with cosmetic results (p = 0.632), but surgeons and external specialists graded significantly better outcomes with TiLOOP(®) Bra (p = 0.034, p = 0.032). CONCLUSION: This pilot study showed use of TiLOOP(®) Bra or Protexa(®) in IBBR is feasible leading to good cosmetic outcomes and high patient satisfaction. To validate the higher failure rates in the Protexa(®) group, data from a larger trial are required. NCT02562170.

Recurrence in a Schuchardt incision after Schauta-Amreich radical vaginal hysterectomy for cervical cancer.

A Schuchardt incision is frequently performed to facilitate access to the parametrium during radical vaginal hysterectomy for cervical cancer. We report an adenocarcinoma recurrence in a Schuchardt incision 12 months after radical vaginal hysterectomy for FIGO stage IB1 cervical cancer. Histology of the primary tumor had shown a well-differentiated adenocarcinoma and poorly differentiated squamous cell carcinoma of the cervix 2.6 cm in maximum diameter. After further surgical therapy and adjuvant radiotherapy, the patient died of disease 51 months after the initial operation. Cervical cancers can implant and recur in perineal incisions. Thus, it appears prudent to avoid such incisions or, if they are made, to irrigate them copiously before closing them.