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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).

Background: The aim of this study was to examine whether EndoPredict (EP), a novel genomic expression test, is effective in predicting local recurrence (LR)-free survival (LRFS) following surgery for breast cancer in postmenopausal women. In addition, we examined whether EP may help tailor local therapy in these patients. Methods: From January 1996 to June 2004, 3714 postmenopausal patients were randomly assigned to either tamoxifen or tamoxifen followed by anastrozole within the prospective ABCSG 8 trial. Using assay scores from EP, we classified breast tumour blocks as either low or high risk for recurrence. Results: Data were gathered from 1324 patients. The median follow-up was 72.3 months and the cumulative incidence of LR was 2.6% (0.4% per year). The risk of LR over a 10-year period among patients with high-risk lesions ( n =683) was significantly higher (LRFS=91%) when compared with patients with low-risk lesions ( n =641) (10-year LRFS=97.5%) (HR: 1.31 (1.16–1.48) P <0.005). The groups that received breast conservation surgery (BCT) and mastectomy (MX) had similar LR rates ( P =0.879). Radiotherapy (RT) after BCT significantly improved LRFS in the cohorts predicted by EP to be low-risk for LR (received RT: n =436, 10-year LRFS 99.8%; did not receive RT: n =63, 10-year LRFS 83.6%, P <0.005). Conclusions: EndoPredict is an effective prognostic tool for predicting LRFS. Among postmenopausal, low-risk patients, EP does not appear to be useful for tailoring local therapy.

BackgroundWhile “no tumour on ink” is an accepted margin width for R0 resection in primary surgery, it’s unclear if it’s oncologically safe after neoadjuvant chemotherapy (NAC). Only limited data demonstrate that surgery within new margins in cases of a pathological complete response (pCR) is safe. We therefore investigated the influence of different margins and pCR on local recurrence and survival rates after NAC.MethodsWe retrospectively analysed data of 406 women with invasive breast cancer, treated with NAC and breast-conserving therapy between 1994 and 2014 in two certified Austrian breast health centres. We compared R ≤ 1 mm, R > 1 mm and RX (pCR) for local recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS).ResultsAfter a median follow-up of 84.3 months, the 5-year LRFS (R ≤ 1 mm: 94.2%, R > 1 mm: 90.6%, RX: 95.0%; p = 0.940), the 5-year DFS (R ≤ 1 mm: 71.9%, R > 1 mm: 74.1%, RX: 87.2%; p = 0.245) and the 5-year OS (R ≤ 1 mm: 85.1%, R > 1 mm: 88.0%, RX: 96.4%; p = 0.236) did not differ significantly between narrow, wide, nor RX resections. Regarding DFS and OS, a negative nodal status reduced the hazard ratio significantly.ConclusionThere is no significant difference in LRFS, DFS and OS comparing close, wide or unknown margins after pCR. We suggest that resection in new margins after NAC is safe according to “no tumour on ink”. Resection of the clipped area in cases of pCR is emphasized.

PurposeIndications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion.MethodsThe panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology.ResultsConsensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.ConclusionsIn case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Background: We investigated whether body mass index (BMI) can be used as a predictive parameter indicating patients who benefit from extended aromatase inhibitor (AI) treatment. Methods: The ABCSG-6a trial re-randomised event-free postmenopausal hormone receptor-positive patients from the ABCSG-6 trial to receive either 3 additional years of endocrine therapy using anastrozole vs nil. In this retrospective analysis, we investigated the prognostic and predictive impact of BMI on disease outcome and safety. Results: In all, 634 patients (177 normal weight, 307 overweight, and 150 obese) patients were included in this analysis. Normal weight patients with additional 3 years of anastrozole halved their risk of disease recurrence (disease-free survival (DFS) HR 0.48; P =0.02) and death (HR 0.45; P =0.06) and had only a fifth of the risk of distant metastases (HR 0.22; P =0.05) compared with normal weight patients without any further treatment. In contrast, overweight+obese patients derived no benefit from additional 3 years of anastrozole (DFS HR 0.93; P =0.68; distant recurrence-free survival HR 0.91; P =0.78; and OS HR 0.9; P =0.68). The possible predictive impact of BMI on extended endocrine treatment could be strengthened by a Cox regression interaction model between BMI and treatment ( P =0.07). Conclusion: Body mass index may be used to predict outcome benefit of extended AI treatment in patients with receptor-positive breast cancer.

Background: Body mass index (BMI) has an impact on survival outcome in patients treated with aromatase inhibitors (AIs). Obesity is associated with an increased body aromatisation and may be a cause of insufficient estradiol depletion. Methods: Sixty-eight postmenopausal oestrogen receptor-positive patients with early breast cancer were prospectively included in this study. Follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were analysed immediately in the clinical routine lab and in a dedicated central lab before (T1) and 3 months after start with aromatase inhibitors (T2). Results: A total of 40 patients were normal or overweight (non-obese: BMI 18.5–29.9 kg m −2 ) and 28 were obese (BMI⩾30 kg m −2 ). Aromatase inhibitors significantly suppressed estradiol serum levels (T1: 19.5 pg ml −1 , T2: 10.5 pg ml −1 , P <0.01) and increased FSH serum levels (T1: 70.2 mIU ml −1 , T2: 75.7 mIU ml −1 , P <0.05). However, after 3 months of AI treatment, estradiol levels of obese patients were nonsignificantly higher compared with non-obese patients (12.5 pg ml −1 vs 9.0 pg ml −1 , P =0.1). This difference was reflected by significantly lower FSH serum levels in obese compared with non-obese patients (65.5 mIU ml −1 vs 84.6 mIU ml −1 , P <0.01). The significant effects of BMI on FSH serum levels could be detected both in the routine as well as in the dedicated central lab. Conclusion: Aromatase inhibitors are less efficient at suppressing estradiol serum levels in obese when compared with non-obese women.

Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test. Results: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours ( P =0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours ( P =0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P =0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P =0.014). Conclusion: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.

Background: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit. Methods: Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy. Results: Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone ( P =0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P =0.012). Interpretation: This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ⩾70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.

Background: Validated multigene signatures (MGS) provide additional prognostic information when evaluating clinical features of ER + , HER2 − early breast cancer. We have studied the quantitative and qualitative impact of MGS on multidisciplinary team (MDT) recommendations. Methods: We prospectively recruited 75 ER + , HER2 − breast cancer patients. Inclusion was based on biopsy assessment of grade, hormone receptor status, HER2, clinical tumour and nodal status. A fresh tissue sample was sent for MammaPrint (MP), TargetPrint analysis at surgery. Clinical risk was decided by the MDT in the absence of MP results and repeated following the collection of MP results. Decision changes were recorded and a health technology assessment was undertaken to compare cost effectiveness. Results: The majority of patients were assigned low to intermediate clinical risk by the MDT. According to MP, 76% were low risk. A very high correlation between local IHC and the TargetPrint assessment was shown. In over a third of patients, discordance between clinical and molecular risk was observed. Decision changes were recorded in half of these cases (18.6%) and resulted in two out of three patients not requiring chemotherapy. The use of MP was also found to be more cost effective. Conclusions: The multigene signature MP revealed clinical and molecular risk discordance in a third of patients. The impact of this on MDT recommendations was most profound in cases where few clinical risk factors were observed and enabled some women to forgo chemotherapy. The use of MGS is unlikely to have an impact in either clinically low-risk women or in patients with more than one relative indication for chemotherapy.