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Introduction: Even though randomized controlled trials could not show a significant survival benefit for the use of neoadjuvant systemic therapy (NST), it is increasingly recommended for patients with clinically node-positive breast cancer due to its implications on prognosis, locoregional downstaging and response-driven adjuvant systemic therapy. The aim of this study was to assess the need for international standardization of treatment recommendations by evaluating clinical practice heterogeneity in use of NST for patients with clinically node-positive breast cancer in Europe. Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) after randomization of the first 500 patients with clinically node-positive breast cancer who underwent axillary lymph node dissection (ALND) or axillary radiation (ART) without ALND after tailored axillary surgery (TAS) in the context of extended regional nodal irradiation. Clinically node-positive breast cancer was defined by confirmed nodal disease at the time of initial diagnosis; in case of neoadjuvant therapy, residual nodal disease was mandatory. Investigators were encouraged to enroll all eligible patients consecutively. However, TAXIS is unique inasmuch as its pragmatic design allows both the neoadjuvant and adjuvant setting according to the preferences of the treating physicians and institutions and thus provides an excellent opportunity to study patterns and trends in use of NST in patients with clinically positive nodes in Europe. Results: A total of 500 patients with a median age of 57 years (IQR: 48-69 years) were included at 44 breast centers in 6 European countries from August 2018 to June 2022. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 393 (80.0%), HR+/HER2+ in 52 (10.6%), HR-/HER2+ in 5 (1.0%) and HR-/HER2- in 34 (6.9%) patients. The rate of patients undergoing NST was 31.4% with a significant upward trend over time during the study period (from 20.0% in 2018 to 38.1% in 2022; p=0.044). The use of NST varied significantly by country (p=< 0.001) and by site (p=0.015). For patients with clinical AJCC tumor stage II and III, the rates of patients undergoing NST in Switzerland were 26.5% (18 of 68) and 35.9% (92 of 256), in Germany 22.2% (2 of 9) and 30.4% (7 of 23), in Austria 50% (7 of 14) and 60% (9 of 15) and in Hungary 0% (0 of 15) and 20.7% (18 of 87), respectively (p=0.019 and 0.004). Large differences by country were found for ER+/HER2- breast cancer, ranging from 13.1% (11 of 84) in Hungary to 47.8% (11 of 23) in Austria (p=0.007). Within Switzerland, which was the country with most included patients (328 of 500) and participating sites (n=25), the rate of patients undergoing NST for ER+/HER2- breast cancer varied considerably by site, ranging from 10% (2 of 20) to 50% (11 of 22). Discussion: This study revealed substantial heterogeneity in clinical practice in Europe, indicating the need for development of and adherence to consistent guidelines to standardize the international use of NST. Citation Format: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Guido Henke, Daniel R. Zwahlen, Günther Gruber, Frank Zimmermann, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Christian Kurzeder, Sherko Küemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Ákos Sávolt, Christian F. Singer, Roland Reitsamer, Jelena Winkler, Giang Thanh Lam Lam, Mathias K. Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Martin Heidinger, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Christoph Tausch. Trends in neoadjuvant systemic therapy rates in Europe: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-14-08.

Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR). We have developed an anti-EGFR targeted nanocontainer drug by inserting anti-EGFR antibody fragments into the membrane of pegylated liposomes (anti-EGFR-ILs-dox). The payload consists of doxorubicin, a standard drug for TNBC. In a first-in-human phase I trial in 26 patients with various advanced solid malignancies, anti-EGFR-ILs-dox has shown little toxicity and encouraging efficacy. In this single-arm phase II trial, we assessed the efficacy of anti-EGFR-ILs-dox as first-line therapy in patients with advanced, EGFR + TNBC. The primary endpoint was progression-free survival at 12 months (PFS12m). Secondary endpoints included overall response rate (ORR), duration of response (DOR), time to progression (TTP), overall survival (OS) and adverse events (AEs). 48 patients received anti-EGFR-ILs-dox 50 mg/m2 iv, on day one of a 28 days-cycle until progression. The Kaplan–Meier estimate for PFS12m was 13% (one-sided 90% CI 7%, 95% CI [5%, 25%]), median PFS was 3.5 months (95% CI 1.9, 5.4). The trial has not reached its primary endpoint. There were no new toxicity signals. Based on these results, anti-EGFR-ILs-dox should not be further developed for TNBC. It remains an open question whether anti-EGFR-ILs-dox would offer more opportunities in other EGFR-expressing malignancies, where targeting this receptor has already shown anticancer effects.Trial registration: This trial was registered at clinicaltrials.gov: NCT02833766. Registered 14/07/2016.

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., Highlights • Tailored axillary surgery is a novel concept for clinically node-positive breast cancer • Tailored axillary surgery selectively removes positive lymph nodes • Tailored axillary surgery is much less radical than axillary dissection • Tailored axillary surgery removes the clipped node in the vast majority of patients

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).

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

Aim: To evaluate the perioperative outcome and cosmetic outcome of prepectoral implant-based breast reconstruction using the TiLOOP® Bra Pocket.Background: Besides acellular dermal matrix (ADM), synthetic meshes have revealed good surgical and aesthetic outcomes. We present our data using TiLOOP® Bra Pocket, a ready-to-use mesh pocket which is made out of nonresorbable, titanized, lightweight polypropylene with a monofilament structure and designed to ensure optimal fixation of the breast implant following mastectomy. The idea behind the mesh pocket is to fix the implant to the muscle and provide coverage and stabilization for the implant by serving as an ´internal bra´, which will create an inferior and lateral sling to support the position and stability of the implant and prevent it from dislocating or twisting. Materials and Methods: A single-center retrospective study was performed to assess short-term complication rates and cosmetic outcomes in patients with immediate or delayed implant-based breast reconstruction using the TiLOOP® Bra Pocket after nipple- or skin-sparing mastectomy. The primary endpoint was complication rates, which were divided into major and minor complications during the first 6 months. Minor complications were defined as those treated conservatively, major complications were those requiring surgical therapy. The secondary endpoint was short-term cosmetic outcome after 6 to 12 months, which was judged by two professionals using the Harvard score (1 = poor, 2 = fair, 3 = good, 4 = excellent). Results: A total of 63 breasts (43 patients) were reconstructed by implant using the TiLOOP® Bra Pocket between 2018 and 2020, of which 57 were immediate reconstructions. Mean follow-up was 12 months. The overall complication rate was 30,2 % (n = 19/63). Major complications occured in 7 breasts (n = 7/63; 11,1 %) and minor complications occured in 12 breasts (12/63; 19,0 %). 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 6 cosmetic revision surgeries were performed (6/63; 9,5 %). Conclusion: Immediate prepectoral implant-based breast reconstruction with the TiLOOP® Bra Pocket seems to be a feasible method with moderate complication rates and good cosmetic outcomes. Careful patient selection and preparation techniques considering flap viability are vital in order to achieve acceptable complication rates and satisfying cosmetic results. Long-term follow-up is needed. The next follow-up will be performed after 24 months. Perioperative OutcomeComplications22Seroma with punction7/63 (11,1%)Seroma without punction1/63 (1,6 %)Hemorrhage2/63 (3,2 %)Nipple necrosis2/63 (3,2 %)Implant Infection3/63 (4,8 %)Skin Infection3/63 (4,8 %)Wound healing deficiency2/63 (3,2 %)Implant loss2/63 (3,2 %)Unplanned resurgery < 3 mo8 (12,7 %) Cosmetic Complication (N=17)Rippling2 (3,2 %)Asymmetry4 (6,3 %)Capsule contracture3 (4,8 %)Fat defects3 (4,8 %)Rotation2 (3,2 %)Cranialisation3 (4,8 %) Cosmetic Outcome (Harvard score; 1 = poor, 2 = fair, 3 = good, 4 = excellent)Observer 13,0 (1 - 4), SD 0,8Observer 23,4 (1-4), SD 0,7 Citation Format: Bich Doan Nguyen, Denise Vorburger, Heike Frauchiger-Heuer, Lilian Bringolf, Nadia Maggi, Julia Talimi-Schnabel, Konstantin Dedes. Prepectoral implant-based breast reconstruction with TiLOOP-bra pocket - a single-center retrospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-64.

Zusammenfassung. Die häufigsten Ursachen einer Brustentzündung (Mastitis) sind bakteriell, durch die üblichen Keime der Hautflora bedingt. Sie sind sowohl bei stillenden als auch bei nicht stillenden Frauen am häufigsten. Klinische Hinweise und eine standardisierte Diagnostik können zur raschen Erkenntnis der seltenen Mastitis-Formen führen. Eine internistische Grunderkrankung oder der Nachweis seltener Krankheitserreger können hinweisend sein. Der wichtigste diagnostische Schritt in der Erkennung seltener Mastitis-Formen ist jedoch die Gewebegewinnung zur histologischen Aufarbeitung. Das inflammatorische Mammakarzinom gilt es bei allen entzündlichen Brusterkrankungen immer auszuschliessen. Dieses MiniReview liefert eine Übersicht zu den seltenen Mastitis-Formen und zeigt, wie das klinische Bild und die eingeleitete Diagnostik zur richtigen Diagnose führen.

Background The effect of anesthetic drugs on cancer outcomes remains unclear. This trial aimed to assess postoperative circulating tumor cell counts—an independent prognostic factor for breast cancer—to determine how anesthesia may indirectly affect prognosis. It was hypothesized that patients receiving sevoflurane would have higher postoperative tumor cell counts. Methods The parallel, randomized controlled trial was conducted in two centers in Switzerland. Patients aged 18 to 85 yr without metastases and scheduled for primary breast cancer surgery were eligible. The patients were randomly assigned to either sevoflurane or propofol anesthesia. The patients and outcome assessors were blinded. The primary outcome was circulating tumor cell counts over time, assessed at three time points postoperatively (0, 48, and 72 h) by the CellSearch assay. Secondary outcomes included maximal circulating tumor cells value, positivity (cutoff: at least 1 and at least 5 tumor cells/7.5 ml blood), and the association between natural killer cell activity and tumor cell counts. This trial was registered with ClinicalTrials.gov (NCT02005770). Results Between March 2014 and April 2018, 210 participants were enrolled, assigned to sevoflurane (n = 107) or propofol (n = 103) anesthesia, and eventually included in the analysis. Anesthesia type did not affect circulating tumor cell counts over time (median circulating tumor cell count [interquartile range]; for propofol: 1 [0 to 4] at 0 h, 1 [0 to 2] at 48 h, and 0 [0 to 1] at 72 h; and for sevoflurane: 1 [0 to 4] at 0 h, 0 [0 to 2] at 48 h, and 1 [0 to 2] at 72 h; rate ratio, 1.27 [95% CI, 0.95 to 1.71]; P = 0.103) or positivity. In one secondary analysis, administrating sevoflurane led to a significant increase in maximal tumor cell counts postoperatively. There was no association between natural killer cell activity and circulating tumor cell counts. Conclusions In this randomized controlled trial investigating the effect of anesthesia on an independent prognostic factor for breast cancer, there was no difference between sevoflurane and propofol with respect to circulating tumor cell counts over time. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Consolidation immunotherapy with the programmed death ligand 1 (PD-L1) inhibitor durvalumab improves survival in patients with stage III non-small-cell lung cancer responding to radiochemotherapy. The aim of this study was to assess the cost-effectiveness of durvalumab in Switzerland based on the most recent PACIFIC survival follow-up. Materials and methods We constructed a Markov model based on the 3-year follow-up data of the PACIFIC trial and compared consolidation durvalumab with observation. We used published utility values and assessed costs for treatment strategies from the perspective of the Swiss health care payers. Cost-effectiveness was tested both in the intention-to-treat population of the PACIFIC trial unselected for PD-L1 tumor expression and in patients with PD-L1-expressing tumors (≥1%). Results In the unselected/PD-L1-positive patients, durvalumab showed an incremental effectiveness of 0.76/1.18 quality-adjusted life year (QALY) and incremental costs of Swiss Francs (CHF) 67 239/78 177, resulting in incremental cost-effectiveness ratios of CHF 88 703/66 131 per QALY gained, respectively. The most influential factors for the incremental cost-effectiveness ratio were the utility before first progression, costs for durvalumab, and the hazard ratio for overall survival under durvalumab versus observation. The cost-effectiveness of durvalumab was better than CHF 100 000 per QALY gained in 75% of the simulations in probabilistic sensitivity analysis. Conclusion Assuming a willingness-to-pay threshold of CHF 100 000 per QALY gained, consolidation durvalumab is likely to be cost-effective both in patients with inoperable stage III non-small-cell lung cancer (NSCLC) unselected for PD-L1 status and in patients with PD-L1-expressing tumors in Switzerland.

Introduction: Chemotherapy is recommended for patients with luminal breast cancer and more than three positive nodes. In addition, recent landmark trials raised the question if the exact number of positive nodes is required to indicate genomic testing. In the neoadjuvant setting, response-driven therapy is increasingly used and may be influenced by surgical staging of the axilla. The present study addressed the role of axillary lymph node dissection (ALND) as decision aid for systemic therapy in a contemporary cohort of patients with clinically node-positive breast cancer in the adjuvant and neoadjuvant setting. Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614). The first 500 patients with clinically node-positive breast cancer who were randomized after tailored axillary surgery (TAS) to undergo ALND or axillary radiotherapy (ART) without ALND in the context of extended regional irradiation were included from August 2018 to June 2022. Clinically node-positive breast cancer was defined by confirmed nodal disease at the time of initial diagnosis; in case of neoadjuvant therapy, the finding of residual nodal disease was mandatory for randomization. TAS consisted of removal of palpably suspicious findings and the sentinel nodes with the option of image guidance. In the ART arm, the total number of positive nodes was not known. We analyzed the impact of ALND on rate and type of systemic therapy. Results: A total of 500 patients with a median age of 57 years (IQR: 48-69 years) were included at 44 breast centers from six European countries. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 393 (80.0%), HR+/HER2+ in 52 (10.6%), HR-/HER2+ in 5 (1.0%) and HR-/HER2- in 34 (6.9%) patients. Of 343 patients (68.6%) who were treated in the adjuvant setting, 297 had HR+/HER2- disease. Of these 297 patients, 145 (48.8%) underwent ART without ALND and 152 (51.2%) underwent ALND after TAS. In the ART arm, the median number of lymph nodes removed was five (IQR 4-8), three (IQR 1-4) of which were positive and in the ALND arm, the number was 19 (IQR 14-26), four (IQR 2-9) of which were positive (p < 0.001). The use of ALND had no significant impact on the rate of patients with HR+/HER2- disease undergoing adjuvant chemotherapy (51.0% in the ART and 57.9% in the ALND arm, p=0.2), and there were no significant differences in type of systemic therapy with the exception of tamoxifen, which was 18.4% with ALND versus 9.0% without (p=0.018). A total of 143 patients (28.6%) underwent neoadjuvant chemotherapy, 13 had neoadjuvant antihormonal treatment and one had neoadjuvant double HER2-blockade without chemotherapy. Of the 143 patients who received neoadjuvant chemotherapy, 71 (49.7%) underwent ART without ALND and 72 (50.3%) underwent ALND. In the ART arm, the median number of lymph nodes removed was four (IQR 3-6), one (IQR 1-3) of which was positive and in the ALND arm, the number was 16 (IQR 12-19), two (IQR 1-5) of which were positive (p < 0.001). The use of ALND in patients after neoadjuvant treatment had no significant impact on the rate of adjuvant systemic therapy (71.8% in the ART and 65.3% in the ALND arm, p=0.4), with no significant differences in type of chemotherapy (e.g., capecitabine: 11.3% vs 12.5%, p=0.8; T-DM1: 11.3% vs. 11.1%, p>0.9) or antihormonal therapy (e.g., aromatase inhibitors: 49.3% vs. 41.7%, p=0.4; tamoxifen: 11.3% vs. 5.6%, p=0.2). Discussion: This study showed that although ALND significantly increased the number of positive nodes removed in the adjuvant and neoadjuvant setting, it had no relevant impact on rate and type of adjuvant systemic therapy. Citation Format: Walter P. Weber, Zoltan Matrai, Stefanie Hayoz, Christoph Tausch, Guido Henke, Daniel R. Zwahlen, Günther Gruber, Frank Zimmermann, Thomas Ruhstaller, Simone Muenst, Markus Ackerknecht, Sherko Küemmel, Vesna Bjelic-Radisic, Viktor Smanykó, Conny Vrieling, Rok Satler, Inna Meyer, Charles Becciolini, Susanne Bucher, Colin Simonson, Peter M. Fehr, Natalie Gabriel, Robert Maráz, Dimitri Sarlos, Konstantin J. Dedes, Cornelia Leo, Gilles Berclaz, Hisham Fansa, Christopher Hager, Klaus Reisenberger, Ákos Sávolt, Christian F. Singer, Roland Reitsamer, Jelena Winkler, Giang Thanh Lam Lam, Mathias K. Fehr, Tatiana Naydina, Magdalena Kohlik, Karine Clerc, Valerijus Ostapenko, Florian Fitzal, Martin Heidinger, Nadia Maggi, Alexandra Schulz, Pagona Markellou, Loïc Lelièvre, Daniel Egle, Jörg Heil, Michael Knauer, Christian Kurzeder. PD15-11 Axillary dissection to determine nodal burden to inform systemic therapy recommendations in patients with clinically node-positive breast cancer: Pre-planned substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-11.

Background: Data on the oncologic safety of omission of axillary lymph node dissection (ALND) in node positive (N+) patients who downstage to ypN0 with neoadjuvant chemotherapy (NAC) is sparse. Additionally, there is no consensus on which axillary staging procedure should be used in this setting, sentinel lymph node biopsy (SLNB) alone or in combination with localization and retrieval of the clipped positive node, also known as targeted axillary dissection (TAD). Whether the reduction in the false negative rate observed with TAD translates into a significant reduction in the rate of axillary recurrence is unknown. We sought to evaluate oncologic outcomes after omission of ALND in a large, real-world cohort of breast cancer (BC) patients and to compare rates of axillary recurrence after SLNB with dual tracer mapping vs. TAD. Methods: Data were collected from 19 centers in the Oncoplastic Breast Consortium (OPBC) and EUBREAST networks. Patients with T1-4 biopsy-proven N1-3 BC who underwent NAC followed by axillary staging with either SLNB with dual tracer mapping or TAD and who were pathologically node negative (ypN0) were included. ypN0 was defined as the absence of any tumor or isolated tumor cells. Competing risk analysis was performed to assess the cumulative incidence rates of axillary recurrence, locoregional recurrence, and any invasive (locoregional or distant) recurrence. Two-year cumulative incidence rates were compared between TAD and SLNB using the Gray’s test. Type I error rate was set to 0.05 (α). Results: We included 785 patients (565 treated with SLNB and 220 with TAD) treated with NAC followed by surgery from 01/2014-12/2020. Median patient age was 50 years. The majority (57%) of patients had clinical T2 tumors, and 95% had N1 disease. Most (55%) were HER2+, and 21% were triple negative. Most patients (81%) received anthracycline and taxane-based chemotherapy regimens, but NAC regimens differed between patients treated with TAD and those treated with SLNB (Table 1). All patients with HER2+ tumors received anti HER2 therapy. Nodal radiotherapy was administered to 76% of patients, and was more common in patients who underwent TAD (82% TAD vs 74% SLNB, p=0.017). Breast pathologic complete response (ypT0/is) was more frequent among those patients that had TAD (80% TAD vs. 66% SLNB, p< 0.001). TAD localization was with wire in 46%, radioactive seed in 40%, ultrasound in 5%, tattoo in 2%, and with a combination of these techniques in 7%. The clipped node was successfully retrieved in 94% of TAD cases. The median number of lymph nodes removed was lower in the TAD group compared to the SLNB group [3 (IQR 3-5) vs 4 IQR 3-5), p< 0.001], as was the median number of sentinel lymph nodes [3 (IQR 2-4) vs 4 IQR 3-5), p< 0.001] (Table 1). The 5-year rates of any axillary recurrence, locoregional recurrence, and any invasive recurrence in the entire cohort were 1.1% (95%CI 0.39-2.4%), 3.1% (95%CI 1.6-5.3%) and 10% (95%CI 7.6-13%), respectively. The two-year cumulative incidence of axillary recurrence did not differ between patients treated with TAD compared to SLNB (0% vs 0.9%, p=0.19). Conclusion: Early axillary recurrence after omission of ALND in patients who successfully downstage from N+ to ypN0 with NAC is a rare event following both SLNB or TAD, and was not significantly lower in TAD than SLNB. Although longer follow-up is needed to confirm these findings, the main advantage of TAD seems to be a reduction in the number of lymph nodes removed. Overall, these results support omission of ALND in patients who successfully downstage to node negative disease after NAC. Table 1: Clinicopathological Features of the Study Cohort, Stratified by Axillary Staging Technique Citation Format: Giacomo Montagna, Mary Mrdutt, Astrid Botty, Andrea V. Barrio, Varadan Sevilimedu, Judy C. Boughey, Tanya L. Hoskin, Laura H. Rosenberger, E Shelley Hwang, Abigail Ingham, Bärbel Papassotiropoulos, Bich Doan Nguyen-Sträuli, Christian Kurzeder, Danilo Diaz Aybar, Denise Vorburger, Dieter Michael Matlac, Edvin Ostapenko, Fabian Riedel, Florian Fitzal, Francesco Meani, Franziska Fick, Jacqueline Sagasser, Jörg Heil, Konstantin J. Dedes, Laszlo Romics, Maggie Banys-Paluchowski, Maria Del Rosario Cueva Perez, Marcelo Chavez Diaz, Martin Heidinger, Mathias K. Fehr, Mattea Reinisch, Nadia Maggi, Nicola Rocco, Nina Ditsch, Oreste Davide Gentilini, Regis Resende Paulinelli, Sebastian Sole Zarhi, Sherko Küemmel, Simona Bruzas, Simona Di Lascio, Tamara Parissenti, Uwe Güth, Valentina Ovalle, Christoph Tausch, Monica Morrow, Thorsten Kühn, Walter P. Weber. Oncological Outcomes Following Omission of Axillary Lymph Node Dissection in Node Positive Patients Downstaging To Node Negative with Neoadjuvant Chemotherapy: the OPBC-04/EUBREAST-06/OMA study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-02.

The aim of this study was to investigate the feasibility, the image quality, and the correlation with histology of dedicated spiral breast computed tomography (B-CT) equipped with a photon-counting detector in patients with suspicious breast lesions after application of iodinated contrast media.The local ethics committee approved this prospective study. Twelve women with suspicious breast lesions found in mammography or B-CT underwent contrast-enhanced spiral B-CT and supplementary ultrasound. For all lesions, biopsy-proven diagnosis and histological workup after surgical resection were obtained including the size of cancer/ductal carcinoma in situ, which were correlated to sizes measured in B-CT. Signal-to-noise ratio and contrast-to-noise ratio were evaluated for tumor, glandular tissue, and fatty tissue.Of the 12 patients, 15 suspicious lesions were found, 14 were malignant, and 1 benign lesion corresponded to a chronic inflammation. All lesions showed strong contrast media uptake with a signal-to-noise ratio of 119.7 ± 52.5 with a contrast-to-noise ratio between glandular tissue and breast cancer lesion of 12.6 ± 5.9. The correlation of the size of invasive tumors measured in B-CT compared with histological size was significant and strong R = 0.77 ( P0.05), whereas the correlation with the size of the peritumoral ductal carcinoma in situ was not significant R = 0.80 ( P = 0.11).Contrast-enhanced B-CT shows high contrast between breast cancer and surrounding glandular tissue; therefore, it is a promising technique for cancer detection and staging depicting both soft tissue lesions and microcalcifications, which might be a substantial advantage over breast MRI.

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.