Prepectoral Versus Subpectoral Implant-Based Breast Reconstruction: A Systemic Review and Meta-analysis.

BACKGROUND: Implant-based breast reconstruction (IBBR) remains the standard and most popular option for women undergoing breast reconstruction after mastectomy worldwide. Recently, prepectoral IBBR has resurged in popularity, despite limited data comparing prepectoral with subpectoral IBBR. METHODS: A systematic search of PubMed and Cochrane Library from January 1, 2011 to December 31, 2021, was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting guidelines, data were extracted by independent reviewers. Studies that compared prepectoral with subpectoral IBBR for breast cancer were included. RESULTS: Overall, 15 studies with 3,101 patients were included in this meta-analysis. Our results showed that patients receiving prepectoral IBBR experienced fewer capsular contractures (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.32-0.92; P = 0.02), animation deformity (OR, 0.02; 95% CI, 0.00-0.25; P = 0.002), and prosthesis failure (OR, 0.58; 95% CI, 0.42-0.80; P = 0.001). There was no significant difference between prepectoral and subpectoral IBBR in overall complications (OR, 0.83; 95% CI, 0.64-1.09; P = 0.19), seroma (OR, 1.21; 95% CI, 0.59-2.51; P = 0.60), hematoma (OR, 0.76; 95% CI, 0.49-1.18; P = 0.22), infection (OR, 0.87; 95% CI, 0.63-1.20; P = 0.39), skin flap necrosis (OR, 0.70; 95% CI, 0.45-1.08; P = 0.11), and recurrence (OR, 1.31; 95% CI, 0.52-3.39; P = 0.55). Similarly, no significant difference was found in Breast-Q scores between the prepectoral and subpectoral IBBR groups. CONCLUSIONS: The results of our systematic review and meta-analysis demonstrated that prepectoral, implant-based, breast reconstruction is a safe modality and has similar outcomes with significantly lower rates of capsular contracture, prosthesis failure, and animation deformity compared with subpectoral, implant-based, breast reconstruction.

The Impact of Adjuvant Radiotherapy on Immediate Prepectoral Implant-Based Breast Reconstruction.

BACKGROUND: Immediate prepectoral implant-based breast reconstruction (IBBR) rates have increased in recent years owing to improved cosmetic and psychological benefits. However, there is a lack of studies regarding complications rates following adjuvant radiotherapy (RT) among patients undergoing immediate prepectoral IBBR. METHODS: We conducted a retrospective monocentric analysis of a cohort of consecutively treated patients who underwent NSM following immediate prepectoral IBBR at our institution between March 2017 and November 2021. Patient demographics, quality of life, complication rates, and oncological safety were evaluated in the RT and non-RT groups. Data analysis was performed using IBM SPSS Version 24 (IMB Corp., Armonk, NY, USA). RESULTS: A total of 98 patients were examined: 70 were assigned to have prepectoral IBBR without RT and 28 to the group who had prepectoral IBBR with RT. There was a statistically significant difference in overall capsular contracture rate between the RT and non-RT group (18% vs. 4.3%, p=0.04). The total implant loss in the cohort was 4% (10.7% vs. 1.4%, p=0.05). We obtained a high percentages of all BREAST-Q categories in both groups; however, satisfaction with the breast and sexual well-being was higher in the non-RT group. The three-year overall survivals were 97.4% in the RT group and 98.5% in the non-RT group. CONCLUSION: Our findings showed that patients in the RT group had a higher rate of capsular contracture and implant loss than those in the non-RT group. However, complication rates were within acceptable range and with accurate preoperative information patients have more benefits from immediate reconstruction showing excellent overall quality of life irrespectively of radiation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Conventional versus reverse sequence of neoadjuvant epirubicin/cyclophosphamide and docetaxel: sequencing results from ABCSG-34.

BACKGROUND: Preoperative chemotherapy containing anthracyclines and taxanes is well established in early-stage breast cancer. Previous studies have suggested that the chemotherapy sequence may matter but definitive evidence is missing. ABCSG trial 34 evaluated the activity of the MUC1 vaccine tecemotide when added to neoadjuvant treatment; the study provided the opportunity for the second randomisation to compare two different anthracycline/taxane sequences. METHODS: HER2-negative early-stage breast cancer patients were recruited to this randomised multicentre Phase 2 study. Patients in the chemotherapy cohort (n = 311) were additionally randomised to a conventional or reversed sequence of epirubicin/cyclophosphamide and docetaxel. Residual cancer burden (RCB) with/without tecemotide was defined as primary study endpoint; RCB in the two chemotherapy groups was a key secondary endpoint. RESULTS: No significant differences in terms of RCB 0/I (40.1% vs. 37.2%; P = 0.61) or pathologic complete response (pCR) rates (24.3% vs. 25%, P = 0.89) were observed between conventional or reverse chemotherapy sequence. No new safety signals were reported, and upfront docetaxel did not result in decreased rates of treatment delay or discontinuation. CONCLUSION: Upfront docetaxel did not improve chemotherapy activity or tolerability; these results suggest that upfront neoadjuvant treatment with anthracyclines remains a valid option.

Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In postmenopausal women with hormone receptor-positive, early-stage breast cancer, treatment with adjuvant aromatase inhibitors is the standard of care, but it increases risk for osteoporosis and fractures. Results from the ABCSG-18 trial showed that use of denosumab as an adjuvant to aromatase inhibitor therapy significantly reduced clinical fractures. Disease-free survival outcomes from ABCSG-18 have not yet been reported. METHODS: Postmenopausal patients with early, hormone receptor-positive, non-metastatic adenocarcinoma of the breast, who had completed their initial adjuvant treatment pathway (surgery, radiotherapy, or chemotherapy, or a combination) and were receiving adjuvant aromatase inhibitors, were enrolled at 58 trial centres in Austria and Sweden into this prospective, double-blind, placebo-controlled, phase 3 trial. With permuted block randomisation (block sizes 2 and 4, stratified by previous aromatase inhibitor use, total lumbar spine bone mineral density score at baseline, and type of centre), patients were assigned (1:1) to receive subcutaneous denosumab (60 mg) or matching placebo every 6 months during aromatase inhibitor therapy. The primary endpoint (previously reported) was the time to first clinical fracture after randomisation. The secondary endpoint reported here is disease-free survival (defined as time from randomisation to first evidence of local or distant metastasis, contralateral breast cancer, secondary carcinoma, or death from any cause) in the intention-to-treat population. This study is registered with EudraCT (number 2005-005275-15) and ClinicalTrials.gov (number NCT00556374), and is ongoing for long-term follow-up. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled and randomly assigned; 1711 to the denosumab group and 1709 to the placebo group (with five others withdrawing consent). After a median follow-up of 73 months (IQR 58-95), 240 (14·0%) patients in the denosumab and 287 (16·8%) in the placebo group had disease-free survival events. Disease-free survival was significantly improved in the denosumab group versus the placebo group (hazard ratio 0·82, 95% CI 0·69-0·98, Cox p=0·0260; descriptive analysis, without controlling for multiplicity). In the denosumab group, disease-free survival was 89·2% (95% CI 87·6-90·8) at 5 years and 80·6% (78·1-83·1) at 8 years of follow-up, compared with 87·3% (85·7-89·0) at 5 years and 77·5% (74·8-80·2) and 8 years in the placebo group. No independently adjudicated cases of osteonecrosis of the jaw or confirmed atypical femoral fractures were recorded. The total number of adverse events was similar in the denosumab group (1367 [including 521 serious] adverse events) and the placebo group (1339 [515 serious]). The most common serious adverse events were osteoarthritis (62 [3·6%] of 1709 in the denosumab group vs 58 [3·4%] of 1690 in the placebo group), meniscus injury (23 [1·3%] vs 24 [1·4%]), and cataract (16 [0·9%] vs 28 [1·7%]). One (<0·1%) treatment-related death (due to pneumonia, septic kidney failure, and cardiac decompensation) occurred in the denosumab group. INTERPRETATION: Denosumab constitutes an effective and safe adjuvant treatment for patients with postmenopausal hormone receptor-positive early breast cancer receiving aromatase inhibitor therapy. FUNDING: Amgen.

Adjuvant Bisphosphonates and Breast Cancer Survival.

Randomized trials have studied bisphosphonates in the adjuvant setting of early breast cancer to investigate their ability to prevent treatment-induced bone loss. Trial results have also suggested their potential to prevent disease recurrence and metastases. These trials are summarized in this review. A recent patient-level meta-analysis by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) finds convincing evidence that adjuvant antiresorptive treatments provide persistent benefits to breast cancer patients in low-estrogen situations and should be considered an important part of the treatment algorithm.

Adjuvant Bisphosphonate Therapy in Postmenopausal Breast Cancer.

OPINION STATEMENT: Bone health and breast cancer are two connected subjects, because breast cancer patients have a higher prevalence of osteopenia/osteoporosis and reduced bone health parameters than healthy woman of the same age. Therefore, the positive effect of adjuvant bisphosphonate therapy plays an important role in breast cancer treatment. Several randomized trials have studied bisphosphonates in the adjuvant setting in postmenopausal woman and demonstrated their potential to prevent treatment-induced bone loss. The prevention of fractures and the subsequent preservation of patients' quality of life are important arguments for the use of adjuvant bisphosphonates in postmenopausal breast cancer patients. In addition, trials of adjuvant bone-targeted agents showed a reduction of recurrences in and outside bone and an improved outcome in patients treated with bisphosphonates.

Objective breast symmetry analysis with the breast analyzing tool (BAT): improved tool for clinical trials.

PURPOSE: Objective cosmetic analysis is important to evaluate the cosmetic outcome after breast surgery or breast radiotherapy. For this purpose, we aimed to improve our recently developed objective scoring software, the Breast Analyzing Tool (BAT®). METHODS: A questionnaire about important factors for breast symmetry was handed out to ten experts (surgeons) and eight non-experts (students). Using these factors, the first-generation BAT® software formula has been modified and the breast symmetry index (BSI) from 129 women after breast surgery has been calculated by the first author with this new BAT® formula. The resulting BSI values of these 129 breast cancer patients were then correlated with subjective symmetry scores from the 18 observers using the Harris scale. The BSI of ten images was also calculated from five observers different from the first author to calculate inter-rater reliability. In a second phase, the new BAT® formula was validated and correlated with subjective scores of additional 50 women after breast surgery. RESULTS: The inter-rater reliability analysis of the objective evaluation by the BAT® from five individuals showed an ICC of 0.992 with almost no difference between different observers. All subjective scores of 50 patients correlated with the modified BSI score with a high Pearson correlation coefficient of 0.909 (p < .001) which was better compared to the old software (r = 0.769; p < .001). CONCLUSIONS: The modified BAT® software improves the correlation between subjective and objective BSI values, and may be a new standard for trials evaluating breast symmetry.

Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. METHODS: In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. FINDINGS: Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. INTERPRETATION: Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. FUNDING: Amgen.

Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers.

BACKGROUND: Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. METHODS: DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples, respectively. The CpG island methylator phenotype (CIMP) was assessed by MethyLight in FFPE material from 78 patients with pT2 and pT3 rectal adenocarcinoma. RESULTS: We identified and confirmed two novel three-gene signatures in fresh frozen samples that can distinguish tumours from adjacent tissue as well as from blood with a high sensitivity and specificity of up to 1 and an AUC of 1. In addition, methylation of individual CIMP markers was associated with specific clinical parameters such as tumour stage, therapy or patients' age. Methylation of CDKN2A was a negative prognostic factor for overall survival of patients. CONCLUSIONS: The newly defined methylation markers will be suitable for early disease detection and monitoring of rectal cancer.

Ptotic versus Nonptotic Breasts in Nipple-sparing Mastectomy and Immediate Prepectoral Breast Reconstruction.

In recent years, nipple-sparing mastectomy followed by implant-based breast reconstruction has gained popularity due to improved cosmetic and psychological benefits. However, patients with ptotic breasts remain the main challenge for surgeons, owing to the potential risk of postoperative complications. Methods: A retrospective chart review was performed for patients who underwent nipple-sparing mastectomy and prepectoral implant-based breast reconstruction between March 2017 and November 2021. Patient demographics, incidence of complications, and quality of life assessed using the BREAST-Q questionnaire were compared between the two different incisions [inverted-T for ptotic versus inframammary fold (IMF) for nonptotic breasts]. Results: A total of 98 patients were examined: 62 in the IMF cohort and 36 in the inverted-T cohort. The results demonstrated equivalence in the safety metrics between the two groups, including hematoma (p=0.367), seroma (p=0.552), infection (P = 1.00), skin necrosis (P = 1.00), local recurrence (P = 1.00), implant loss (P = 0.139), capsular contracture (P = 1.00), and nipple-areolar complex necrosis (P = 0.139). The BREAST-Q scores were equally high in both groups. Conclusion: Our results suggest that inverted-T incision for ptotic breasts is a safe modality with similar complication rates and high aesthetic results compared with IMF incision for nonptotic breasts. A higher rate of nipple-areolar complex necrosis in the inverted-T group, although not significant, should be considered during careful preoperative planning and patient selection.

Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer.

Based upon results of the KEYNOTE-522 trial and following approval by regulatory authorities, the addition of pembrolizumab to chemotherapy is now the standard-of-care for the treatment of early triple-negative breast cancer (eTNBC) (Clinical stage II-III). Pembrolizumab is a programmed cell death protein 1 monoclonal antibody, known to cause immune-related adverse events (irAEs) in a significant subset of patients. Real-world data on incidence, type and treatment strategies of irAEs in the setting of eTNBC treatment are sparse. In this multicenterretrospective analysis, we characterized real-world incidence of irAEs and treatment outcomes such as pathological complete response (pCR) from the combination of pembrolizumab and chemotherapy as neoadjuvant treatment for eTNBC. We found a rate of irAEs of all grades of 63.9% and of 20% for irAEs of grade 3 or higher. In the overall population, a pCR rate of 57.1% was observed. The emergence of irAEs correlated significantly with pCR (72.2% versus 30.8%; p =.03). Discontinuation of neoadjuvant chemotherapy before week 12 correlated significantly with a lower pCR rate. To our knowledge, this is the first study evaluating the real-world efficacy and safety of a neoadjuvant combination of chemotherapy and pembrolizumab in eTNBC, demonstrating a significant correlation between irAEs and pCR. Early discontinuation of neoadjuvant therapy due to AEs resulted in a lower pCR rate.

Differential immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel in breast cancer patients.

BACKGROUND: Epirubicin/cyclophosphamide (EC) and docetaxel (D) are commonly used in a sequential regimen in the neoadjuvant treatment of early, high-risk or locally advanced breast cancer (BC). Novel approaches to increase the response rate combine this treatment with immunotherapies such as PD-1 inhibition. However, the expected stimulatory effect on lymphocytes may depend on the chemotherapy backbone. Therefore, we separately compared the immunomodulatory effects of EC and D in the setting of a randomized clinical trial. METHODS: Tumor and blood samples of 154 patients from the ABCSG-34 trial were available (76 patients received four cycles of EC followed by four cycles of D; 78 patients get the reverse treatment sequence). Tumor-infiltrating lymphocytes, circulating lymphocytes and 14 soluble immune mediators were determined at baseline and at drug change. Furthermore, six BC cell lines were treated with E, C or D and co-cultured with immune cells. RESULTS: Initial treatment with four cycles of EC reduced circulating B and T cells by 94% and 45%, respectively. In contrast, no comparable effects on lymphocytes were observed in patients treated with initial four cycles of D. Most immune mediators decreased under EC whereas D-treatment resulted in elevated levels of CXCL10, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR). Accordingly, only the exposure of BC cell lines to D induced similar increases as compared to E. While treatment of BC cells with E was associated with cell shrinkage and apoptosis, D induced cell swelling and accumulation of cells in G2 phase. CONCLUSION: The deleterious effect of EC on lymphocytes indicates strong immunosuppressive properties of this combination therapy. D, in contrast, has no effect on lymphocytes, but triggers the secretion of stimulatory proteins in vivo and in vitro, indicating a supportive effect on the immune system. Underlying differences in the induced cell death might be causal. These divergent immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel should be considered when planning future combinations with immunotherapies in breast cancer.

Influence of Height on Risk and Outcome of Patients with Early Breast Cancer: A Pooled Analysis of 4,925 Patients from 5 Randomized Trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG).

Background: Associations between height, cancer risk and worse outcome have been reported for several cancers including breast cancer. We hypothesized that in breast cancer clinical trials, tall women should be overrepresented and might have worse prognosis. Methods: Data of 4,935 women, included from 1990 to 2010 in 5 trials of the Austrian Breast and Colorectal Cancer Study Group (ABCSG), were analyzed retrospectively. The primary objective was to determine differences in height distribution between the ABCSG cohort and the Austrian female population according to a cross-sectional health survey conducted by the Austrian Statistic Center in 2006 and 2007. Secondary endpoints were disease-free survival (DFS) and overall survival (OS) in different height classes and differences of body mass index (BMI) distribution. Results: Breast cancer patients in the ABCSG cohort were only slightly but statistically significantly smaller compared to unselected Austrian adult females (mean 164.3 vs. 164.8 cm; p < 0.0001) and significantly more patients were seen in the lower body height class (50 vs. 46%; p < 0.0001) when using the median as a cutoff. However, after adjustment for age, the difference in body height between the two cohorts was no longer significant (p = 0.089). DFS and OS in the two upper height groups (≥170 cm) compared to the two lowest height groups (<160 cm) was not significantly different (5-year DFS: 84.7 vs. 83.0%; HR 0.91, 95% CI 0.73-1.13, p = 0.379; 5-year OS: 94.8 vs. 91.7%; HR 0.74, 95% CI 0.55-1.00, p = 0.051). The BMI of ABCSG patients was significantly higher than in the reference population (mean BMI 24.64 vs. 23.96; p < 0.0001). Conclusions: Our results do not confirm previous findings that greater body height is associated with a higher breast cancer risk and worse outcome.

Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders.

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. SIGNIFICANCE: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275.

Androgen Receptor is Expressed in Breast Cancer Brain Metastases.

BACKGROUND: Androgen receptor (AR) expression is a potential therapeutic target in breast cancer (BC) as it is frequently expressed in the luminal A and B subtypes and in approximately one third of basal-like cancers. As AR-positive BC displays a distinct biological behavior, we aimed to analyze AR expression in the particular context of BC brain metastases (BM). MATERIALS AND METHODS: Patients with newly diagnosed BC BM treated with neurosurgical resection were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, biological tumor subtypes and overall survival were obtained by retrospective chart review. Formalin-fixed and paraffin-embedded specimen containing BM tissue were retrieved from the Neuro-Biobank. Immunohistochemical staining of AR was performed and AR expression in the tumor-cell nucleus was evaluated. RESULTS: Fifty-seven BM samples from 57 individual patients with BC were available for this analysis. AR expression of ≥1% tumor cells was evident in 20/57 (35.1%) BM specimens; the median AR-expression rate was 10% (range: 1% to 60%). AR expression was observed in 11/21 (52.4%) BM of the luminal/human epidermal growth factor receptor 2 (HER2)-negative subtype, 3/13 (23.1%) of the luminal/HER2-positive subtype, 2/7 (28.6%) of the HER2-positive subtype and 4/16 (25.0%) of the triple-negative subtype (P=0.247). Median survival from diagnosis of BM was 10 months (range: 0 to 104 mo) in the entire cohort. No significant association of overall survival and AR expression ≥1% was observed (15 vs. 13 mo; P>0.05). CONCLUSION: AR is expressed in more than one third of BC BM with the highest rates among the luminal/HER2-negative BC subtype and may therefore be a potential prognostic and predictive biomarker in this particular BC population.

Favourable outcome of patients with breast cancer brain metastases treated with dual HER2 blockade of trastuzumab and pertuzumab.

BACKGROUND: Dual human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab and pertuzumab (TP) is a standard therapy of metastatic and localized HER2-positive breast cancer (BC), but its activity in breast cancer brain metastases (BCBM) is unknown. METHODS: Patients with HER2-positive BCBM were identified from the Vienna Brain Metastasis Registry and clinical data including patient characteristics, therapies and overall survival (OS) were obtained. Patients were grouped into 'TP', 'other-HER2-targeted therapy' and 'no-HER2-targeted therapy' according to received first-line systemic therapy after diagnosis of BCBM. Radiological re-assessment of intracranial lesions was performed in patients treated with TP as systemic first-line therapy according to RANO response criteria for brain metastases (BM). RESULTS: A total of 252 HER2-positive BC patients with BM were available for this analysis. Patients treated with TP as systemic first-line therapy after diagnosis of BM had a significantly longer OS compared with treatment with other-HER2-targeted therapy and no-HER2-targeted therapy (44 versus 17 versus 3 months, p < 0.001; log-rank test). Among radiologically re-assessed patients treated with TP as systemic first-line therapy after diagnosis of BM, 5/14 patients (35.7%) had complete intracranial remission (CR), 8/14 patients (57.1%) partial intracranial remission (PR), 1/14 patients (7.1%) stable intracranial disease (SD) and 0/14 patients (0.0%) progressive intracranial disease (PD) as best response resulting in an intracranial objective response rate (iORR) of 92.9% and an intracranial clinical benefit rate (iCBR) of 100.0%. CONCLUSION: First-line therapy with dual HER2-inhibition of TP after BM diagnosis was associated with the longest median OS times in patients with BCBM.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

AIM: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. METHODS: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. RESULTS: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. CONCLUSIONS: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Efficacy and safety of the therapeutic cancer vaccine tecemotide (L-BLP25) in early breast cancer: Results from a prospective, randomised, neoadjuvant phase II study (ABCSG 34).

BACKGROUND: Immune-based strategies represent a promising approach in breast cancer (BC) treatment. The glycoprotein mucin-1 (MUC-1) is overexpressed in more than 90% of BC patients, and is targeted by the cancer vaccine tecemotide. We have investigated the efficacy and safety of tecemotide when added to neoadjuvant standard-of-care (SoC) treatment in early BC patients. PATIENTS AND METHODS: A total of 400 patients with HER2-early BC were recruited into this prospective, multicentre, randomised 2-arm academic phase II trial. Patients received preoperative SoC treatment (chemotherapy or endocrine therapy) with or without tecemotide. Postmenopausal women with oestrogen receptor (ER)+++, or ER++ and Ki67 < 14%, and G1,2 tumours ('luminal A' tumours) received 6 months of letrozole. Postmenopausal patients with triple-negative, ER-/+/++ and Ki67 ≥ 14%, and with G3 tumours, as well as premenopausal patients, received four cycles of epirubicin/cyclophosphamide plus four cycles of docetaxel. Primary end-point was residual cancer burden (RCB; 0/I versus II/III) at surgery. Secondary end-points included pathological complete response (pCR), safety, and quality of life. FINDINGS: We observed no significant difference in RCB 0/I rates between patients with (36.4%) and without (31.9%) tecemotide in the overall study population (p = 0.40) nor in endocrine and chemotherapy-treated subgroups (25.0% versus 13.3%, p = 0.17; 39.6% versus 37.8%, p = 0.75, respectively). The addition of tecemotide did not affect overall pCR rates (22.5% versus 17.4%, p = 0.23), MUC-1 expression, or tumour-infiltrating lymphocytes content. Tecemotide did not increase toxicity when compared to SoC therapy alone. INTERPRETATION: Neoadjuvant tecemotide is safe, but does not improve RCB or pCR rates in patients receiving standard neoadjuvant therapy.

Continued Endocrine Therapy Is Associated with Improved Survival in Patients with Breast Cancer Brain Metastases.

PURPOSE: Brain metastases (BMs) are a rare but devastating condition in estrogen receptor (ER)-positive metastatic breast cancer (MBC). Although endocrine therapy (ET) is the mainstay of treatment in this disease subtype, only case reports have been published concerning the activity of ET in BMs henceforth. Therefore, we aimed to systematically investigate the impact of ET after diagnosis of BM on outcome and clinical course of disease in patients with ER-positive MBC. EXPERIMENTAL DESIGN: Patient characteristics, detailed information about BMs including diagnosis-specific graded prognostic assessment class (DS-GPA), and clinical outcome were obtained by retrospective chart review for all patients treated for ER-positive breast cancer BMs between 1990 and 2017 at an academic care center. Overall survival (OS) was measured as the interval from diagnosis of BM until death or last date of follow-up. RESULTS: Overall, 198 patients [female: 195/198 (98.5%); male: 3/198 (1.5%)] with ER-positive breast cancer BMs were available for this analysis. Eighty-eight of 198 patients (44.4%) received ET after diagnosis of BM including aromatase inhibitors (AIs; letrozole, anastrozole, exemestane), tamoxifen, and fulvestrant. Median OS was significantly longer in patients receiving ET after diagnosis of BM compared with patients who did not (15 vs. 4 months, P < 0.001; log-rank test). No significant difference in terms of OS was observed between patients receiving AIs, tamoxifen, or fulvestrant. In patients with concomitant leptomeningeal carcinomatosis (LC), ET prolonged median OS significantly as well (7 vs. 3 months, P = 0.012; log-rank test). In a multivariate analysis including DS-GPA and ET, only treatment with ET after diagnosis of BM (HR, 0.69; 95% confidence interval, 0.48-0.99; P = 0.046) was associated with prognosis (Cox regression model). CONCLUSIONS: Continuing ET after BM diagnosis was associated with a significantly prolonged OS in this large single-center cohort. No substantial differences between substances were observed. These findings should be validated in a prospective cohort.

Local therapies for breast cancer.

During the San Antonio Breast Cancer Symposium in December 2016, the main topics were systemic treatment of breast cancer and molecular research. But several studies were also presented concerning local therapy: Surgical issues on evaluating resection margins, management of ductal carcinoma in situ (DCIS), surgical challenges after neoadjuvant therapy related to assessment of response or treatment of axillary lymph nodes, and studies about outcome after breast reconstruction and radiation therapy were discussed. In this short review, oral presentations of these topics are summarized.