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Aims and objectives: The purpose of this study was to assess the feasibility of using the single-incision round block technique in breast-conserving surgery with sentinel lymph node (SLN) retrieval for breast cancer without compromising oncological safety. Materials and methods: A retrospective observational case-control study was conducted from January 2017 to October 2021. The study population consisted of two groups. In both groups, breast-conserving surgery was carried out through the round-block technique. In group A, SLN retrieval was performed using the round-block incision (study group), while in group B, SLN retrieval was conducted through a second skin incision in the axilla (control group). The study was approved by the local ethics committee Zurich (BASEC-Nr. 2020-02857), and written informed consent was obtained from all participants. Results: Overall, 134 patients met the inclusion criteria, of whom 86 women underwent breast-conserving surgery and SLN retrieval using the single-incision approach (group A), and 48 women underwent conventional surgery, using two independent incisions for tumour resection and SLN retrieval (group B). The overall success rate in group A regarding SLN retrieval was 97.7%, whereas most tumours were located in the upper outer (47.7%) and upper inner quadrant (27.9%). Although the technique was equally successful in the other quadrants, the share of tumours in the lower outer, and the lower inner quadrant, and the retroareolar region was smaller, representing 17.4%, 3.5% and 3.5%, respectively. The median number of dissected lymph nodes was two, with a positivity rate of 24.4%. The occurrence of axillary neuralgia and axillary skin retraction was significantly higher in group B along with tendentially more axillary seroma formation. There were no significant differences regarding reintervention rates, in terms of complications, resection margins, locoregional recurrences, or deaths with a mean follow-up of 11 months. Conclusio

Augmentation mammoplasty using hydrogel fillers such as polyacrylamide gel (PAAG) or Aquafilling® has been performed commonly in some countries as an alternative to breast augmentation with saline or silicone implants. However, the safety of this procedure remains controversial, and many complications associated with the use of large-volume hydrogel injection have been reported in recent years. We present the case of a 33-year-old woman with a history of bilateral Aquafilling® injection augmentation mammoplasty who presented with an enlarged left breast while breastfeeding. Based on the clinical presentation and ultrasound findings, the patient underwent surgical incision as abscess formation caused by infection of the filler material could not be ruled out with certainty. Surgery revealed a galactocele with drainage of large amounts of milky fluid. Remaining filler material was removed as thoroughly as possible, and vacuum assisted wound dressing was performed. Galactocele formation in lactating women is a known complication after injection of hydrogel. Hence, it is important to be familiar with this uncommon but possibly severe complication in order to make an accurate diagnosis and initiate adequate treatment. To that end, it is recommended that patients who underwent Aquafilling® injection for breast augmentation should avoid lactation and that women intending to breastfeed should not undergo augmentation mammoplasty with injection of Aquafilling®.Level of Evidence: Level V, risk / prognostic study

Background: Prepectoral implant-based reconstruction using synthetic meshes is feasible with good outcomes. We present our data using TiLOOP® Bra Pocket, a novel ready-to-use mesh pocket which acts as an internal bra and prevents the implant from dislocating or twisting. Materials and methods: A single-centre retrospective cohort study was performed to assess short-term complication rates and cosmetic outcomes in patients with prepectoral implant-based reconstruction using the TiLOOP® Bra Pocket. The primary endpoint was complication rates during the first 6 months. The secondary endpoint was the cosmetic outcome after 6 to 12 months, which was judged by two breast surgeons using the Harvard score. Results: A total of 63 breasts (43 patients) were reconstructed using the TiLOOP® Bra Pocket between 2018 and 2020, 57 were immediate reconstructions. The overall complication rate was 30,2% (n = 19/63). Major complications occurred in seven breasts (n = 7/63; 11,1%) and minor complications occurred in 12 breasts (12/63; 19,0%). The unplanned revision rate was 12,7%. The cosmetic outcome was good (Harvard score: mean 3, range 1-4; SD 0,75). Seventeen cosmetic complications were observed (17/63; 27,0%) and six cosmetic revision surgeries were performed (6/63; 9,5%). Conclusion: The use of the TiLOOP® Bra Pocket is convenient and standardized because the pocket is preformed and does not require to be sewn first. Cosmetic outcome is good; however, the surgical morbidity needs to be addressed in future reconstructions. Careful patient selection and preparation techniques are vital in order to achieve acceptable complication rates and satisfying cosmetic results. Keywords: Implant; Mesh; Prepectoral breast reconstruction; TiLOOP® Bra Pocket.

Metastatic breast cancer is considered an incurable disease. Targeted treatments against the human epidermal growth factor receptor 2 (HER2), however, significantly improve survival in patients with metastatic HER2-positive breast cancer. Some patients may respond with prolonged complete remission. Evidence on safety of long-term trastuzumab and risk of relapse after trastuzumab cessation is limited. We present a case of an 81-year-old patient with HER2-amplified metastatic breast cancer (MBC) in the liver. Following taxane-based chemotherapy in combination with trastuzumab after local treatment resulted in a complete radiological remission after 21months of trastuzumab maintenance therapy. The patient remains in complete remission 6years later and continues to receive trastuzumab as maintenance therapy. Prolonged remission in cases with complete response under trastuzumab-based regimens for metastatic HER2-positive breast cancer can be observed in some patients. Reviewing the few available cases published in the literature, these patients share some common characteristics: hormone receptor negative disease and metastases to the liver. There is no evidence that trastuzumab maintenance treatment can be safely interrupted after a certain time period.

PARP inhibitors are used for treatment of tumors lacking function of the double-strand DNA break repair proteins BRCA1 or BRCA2 and are already approved for several cancer types. Thus, it is clinically crucial to determine germline as well as somatic BRCA1/2 mutations in those patients. The amplicon-based Oncomine BRCA1 and BRCA2 Assay is a test routinely used in diagnostics with FFPE specimens. The assay is validated for the detection of mutations, however, data on its performance in detecting large genomic rearrangements in FFPE tissue, is scarce. We cross-validated Oncomine BRCA1 and BRCA2 Assay in blood samples and/or FFPE tissue with multiplex ligation-dependent probe amplification (MLPA) for exon deletions and with OncoScan and an in-house hybridization-based target capture assay (MelArray) with a customized pipeline for the detection of loss of heterozygosity (LOH) and heterozygous versus complete gene loss. The Oncomine BRCA1 and BRCA2 Assay could detect both exon deletion and mono- and bi-allelic losses of the BRCA1/2 genes. We show that the therapeutically relevant large genomic rearrangements are reliably detected with the amplicon-based Oncomine BRCA1 and BRCA2 Assay in FFPE tumor tissue. Based on our data, we suggest tumor BRCA testing as standard diagnostic prescreening prior to germline BRCA testing.

Background: The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. Methods: In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0-N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. Results: Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt . Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17-0.88) P = 0.0091. Conclusion: TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. Trial registration: ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

SummaryIn the randomised TARGIT-A trial, risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy was non-inferior to whole-breast external beam radiotherapy, for local recurrence. In the long-term, no difference was found in any breast cancer outcome, whereas there were fewer deaths from non-breast-cancer causes. TARGIT-IORT should be included in pre-operative consultations with eligible patients.

Objective: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer. Design: Prospective, open label, randomised controlled clinical trial. Setting: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada. Participants: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT). Interventions: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients). Main outcome measures: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes. Results: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference w

Ectopic breast tissue can persist in the axilla due to lack of involution of mammary glands along the mammary lines. It is rare in men, and the malignant transformation to breast cancer has occasionally been described. Differential diagnosis of any axillary tumor should include breast cancer arising at ectopic sites.

Juvenile papillomatosis (JP), the so-called Swiss cheese disease is a rare benign breast disease of young adults. An association (up to 28 %) with breast-cancer within the family of affected patients has been reported. A multinodular cystic breast-mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal-papillomas, usual ductal hyperplasia (UDH), ductectasias, perifocal sclerosing adenosis and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family-history in context with a comprehensive review of JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were female with a median-age of 38 years (26 to 50 years). Follow-up information was available in 11 of 13 patients. Sufficient paraffin embedded tissue and good DNA quality for next generation sequencing (NGS) was available in 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease, the tissue cores underwent NGS analysis using Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations, in 2 of 10 patients AKT1 mutations in known hotspot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1 and GNAS genes were detected in individual patients. Some of these mutations were present at high allelic frequencies suggesting germ line mutations. 2 of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hotspot mutations in PIK3CA and AKT1 genes in JP associated with p

AIM: To evaluate the frequency of loss of mediator of DNA damage checkpoint protein 1 (MDC1) protein expression in endometrial cancer (EC) and to determine whether loss of MDC1 is associated with certain clinicopathological parameters. MATERIALS AND METHODS: MDC1 expression was examined in 426 samples of EC. The nuclear immunoreactivity of the protein was defined as: negative, weak, moderate and strong. RESULTS: Loss of MDC1 expression (defined as negative nuclear staining) was found in 8.9% (38/426) of ECs and was significantly associated with the loss of MRE11 homolog, double-strand break repair nuclease, RAD50 double-strand break repair protein and nibrin complex components. In addition, loss of expression of MDC1 showed a significant correlation with any mismatch repair deficiency, with endometrioid histological subtype and low tumour grading. CONCLUSION: Based on these findings, we suggest that MDC1 loss frequently occurs in ECs with microsatellite instability. Due to deficient homologous recombination DNA repair, MDC1-negative ECs might show an increased sensitivity to poly(ADP-ribose) polymerase-inhibitory therapy.

BACKGROUND Since the advent of high-throughput sequencing technologies, organised germline screening, independent of the personal and family cancer history, has been frequently proposed. Since ethnic and geographic populations significantly differ in their mutation spectra and prevalence, one critical prerequisite would be the knowledge of the expected carrier frequencies. OBJECTIVE For the first time, in a retrospective non-cancer related cohort from a single Swiss genetic centre, we systematically assessed the prevalence of secondary findings in 19 genes (BRCA1/2 plus 17 non-BRCA genes) previously designated by the US National Comprehensive Cancer Network (NCCN) for hereditary breast and ovarian cancer (HBOC) germline testing. DESIGN A total of 400 individuals without a cancer diagnosis undergoing whole-exome sequencing (WES) analysis for neurodevelopmental disorders (NDDs) from 2015 to 2017 at IMG Zurich were included after quality assessment. Among these, 180 were unaffected parental couples, 27 unaffected parental singles and 13 NDD index patients (mean age 43 years). The majority of the cohort was of Caucasian ethnicity (n = 336, 84.0%) and of Northwest European ancestry (n = 202, 50.5%), for 70 of whom (42.5%) an autochthonous Swiss descent was assumed. For WES filtering of rare, potentially actionable secondary variants in HBOC genes, an overall minor allele frequency (MAF) below 0.65% was used as cut-off. Each rare variant was manually evaluated according to the recommended ACGM-AMP standards, with some adaptations including “hypomorphic” as an additional distinct pathogenicity class. RESULTS Overall, 526 rare secondary variants (339 different variants) were encountered, with the BRCA1/2 genes accounting for 27.2% of the total variant yield. If stratified for variant pathogenicity, for BRCA1/2, three pathogenic variants were found in three females of Italian ancestry (carrier frequency of 0.8%). In the non-BRCA genes, five carriers of (likely) p