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Simple Summary: Historically, all patients with breast cancer (BC) underwent radical removal of lymph nodes under the armpit and up to the neck. Since the 1990s, axillary surgery has become increasingly de-escalated, and few indications for axillary lymph node dissection (ALND) remain. Patients with small BC (<2 cm) and unremarkable clinical examination through palpation and ultrasound may safely forego any axillary surgery. For patients with clinically node-negative BC and up to two positive lymph nodes found on sentinel lymph node biopsy, ALND can be safely avoided. If no residual tumor cells are found in the lymph nodes after neoadjuvant chemotherapy (NACT), ALND is not necessary. Ongoing studies are investigating whether axillary radiotherapy can provide similar survival outcomes to ALND in patients with clinically node-positive BC or in patients with residual nodal disease after NACT. Axillary surgery for patients with breast cancer (BC) in 2024 is becoming increasingly specific, moving away from the previous 'one size fits all' radical approach. The goal is to spare morbidity whilst maintaining oncologic safety. In the upfront surgery setting, a first landmark randomized controlled trial (RCT) on the omission of any surgical axillary staging in patients with unremarkable clinical examination and axillary ultrasound showed non-inferiority to sentinel lymph node (SLN) biopsy (SLNB). The study population consisted of 87.8% postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative BC. Patients with clinically node-negative breast cancer and up to two positive SLNs can safely be spared axillary dissection (ALND) even in the context of mastectomy or extranodal extension. In patients enrolled in the TAXIS trial, adjuvant systemic treatment was shown to be similar with or without ALND despite the loss of staging information. After neoadjuvant chemotherapy (NACT), targeted lymph node removal with or without SLNB showed a lower false-negative rate to determine nodal pathological complete response (pCR) compared to SLNB alone. However, oncologic outcomes do not appear to differ in patients with nodal pCR determined by either one of the two concepts, according to a recently published global, retrospective, real-world study. Real-world studies generally have a lower level of evidence than RCTs, but they are feasible quickly and with a large sample size. Another global real-world study provides evidence that even patients with residual isolated tumor cells can be safely spared from ALND. In general, few indications for ALND remain. Three randomized controlled trials are ongoing for patients with clinically node-positive BC in the upfront surgery setting and residual disease after NACT. Pending the results of these trials, ALND remains indicated in these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Neoadjuvant treatment refers to therapy given before surgery for early-stage breast cancer. It has several benefits, especially for patients with specific subtypes like HER2+ and triple-negative cancers. By using neoadjuvant treatment, tumors can shrink before surgery, allowing for less invasive surgical procedures in the breast and axilla. Achieving complete tumor disappearance after neoadjuvant treatment is associated with better survival outcomes. Researchers studied 92 patients initially diagnosed with node-positive disease. A key finding is that patients with HER2+ and triple-negative subtypes who have achieved complete tumor disappearance in the breast have a higher chance of achieving complete tumor disappearance in the axilla, which allows for less aggressive axillary surgery. In this study, more than half the patients did not need a removal of all the nodes in the axilla. In summary, neoadjuvant treatment improves outcomes, reduces surgical morbidity, and benefits patients with HER2+ and triple-negative subtypes. Neoadjuvant systemic treatment (NST) is the standard treatment for HER2+, triple-negative (TN), and highly proliferative luminal HER2− early breast cancer. Pathologic complete response (pCR) after NST is associated with improved outcomes. We evaluated the predictive factors for axillary-pCR (AXpCR) and its impact on the extent of axillary node surgery. This retrospective study included 92 patients (median age of 50.4 years) with an initially node-positive disease. Patients were treated with molecular subtype-specific NST (4.3% were luminal A-like, 28.3% luminal HER2−, 26.1% luminal HER2+, 18.5% HER2+ non-luminal, and 22.8% TN). Axillary-, breast- and total-pCR were achieved in 52.2%, 48.9%, and 38% of patients, respectively. In a binary logistic regression model for the whole population, the only independent factor significantly associated with AXpCR was breast-pCR (OR 7.4; 95% CI 2.6–20.9; p < 0.001). In patients who achieved breast-pCR, aggressive subtypes (HER2+ and TN; OR 11.24) and clinical tumor stage (OR 0.10) had a significant impact on achieving AXpCR. Axillary lymph node dissection was avoided in 53.3% of patients. In conclusion, in node-positive patients with HER2+ and TN subtypes, who achieved breast-pCR after NST, de-escalation of axillary surgery could be considered in most cases. [ABSTRACT FROM AUTHOR]

Background: The Choosing Wisely initiative recommended the omission of routine sentinel lymph node biopsy (SLNB) in patients ≥ 70 years of age, with clinically node-negative, early stage, hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her2) negative breast cancer in August 2016. Here, we assess the adherence to this recommendation in a Swiss university hospital. Methods: We conducted a retrospective single center cohort study from a prospectively maintained database. Patients ≥ 18 years of age with node-negative breast cancer were treated between 05/2011 and 03/2022. The primary outcome was the percentage of patients in the Choosing Wisely target group who underwent SLNB before and after the initiative went live. Statistical significance was tested using chi-squared test for categorical and Wilcoxon rank-sum tests for continuous variables. Results: In total, 586 patients met the inclusion criteria with a median follow-up of 2.7 years. Of these, 163 were ≥ 70 years of age and 79 were eligible for treatment according to the Choosing Wisely recommendations. There was a trend toward a higher rate of SLNB (92.7% vs. 75.0%, p = 0.07) after the Choosing Wisely recommendations were published. In patients ≥ 70 years with invasive disease, fewer received adjuvant radiotherapy after omission of SLNB (6.2% vs. 64.0%, p < 0.001), without differences concerning adjuvant systemic therapy. Both short-term and long-term complication rates after SLNB were low, without differences between elderly patients and those < 70 years. Conclusions: Choosing Wisely recommendations did not result in a decreased use of SLNB in the elderly at a Swiss university hospital. [ABSTRACT FROM AUTHOR]

Axillary surgery in patients with breast cancer has been a history of de-escalation; however, surgery for clinically node-positive breast cancer remained at the dogmatic level of axillary lymph node dissection (ALND). In these patients, currently the only way to avoid ALND is neoadjuvant systemic treatment (NST) with nodal pathologic complete response (pCR) as diagnosed by selective lymph node removal. However, pCR rates are highly dependent on tumor biology, with luminal tumors being most present yet showing the lowest pCR rates. Therefore, the TAXIS trial is investigating whether in clinically node-positive patients, either with residual disease after NST or in the upfront surgical setting, ALND can be safely omitted. All patients undergo tailored axillary surgery (TAS), which includes removal of the biopsied and clipped node, the sentinel lymph nodes as well as all palpably suspicious nodes, turning a clinically positive axilla into a clinically negative. Feasibility of TAS was recently confirmed in the first pre-specified TAXIS substudy. TAS is followed by axillary radiotherapy to treat any remaining nodal disease. Disease-free survival is the primary endpoint of this non-inferiority trial, and morbidity as well as quality of life are the main secondary endpoints, with ALND being known for having a relevant negative impact on both. Currently, 663 of 1500 patients were randomized; accrual completion is projected for 2025. The TAXIS trial stands out in including clinically node-positive patients in both the neoadjuvant and upfront surgery setting, thereby investigating surgical de-escalation at the far-end of the risk spectrum of patients with breast cancer. • Axillary lymph node dissection is currently indicated in most patients with clinically node-positive disease. • The TAXIS trial investigates the de-escalated concept of tailored axillary surgery. • Tailored axillary surgery reduces the tumor load in the axilla to the point where radiation should be able to control it. • TAXIS accrual completion is projected for 2025 and primary endpoint analysis for 2029. [ABSTRACT FROM AUTHOR]

Simple Summary: Most breast cancers are small and can be treated using breast-conserving surgery. Since these tumors are non-palpable, they require a localization step that helps the surgeon to decide which tissue needs to be removed. The oldest localization technique is a guidewire placed into the tumor before surgery, usually using ultrasound or mammography. Afterwards, the surgeon removes the tissue around the wire tip. However, this technique has several disadvantages: It can cause the patient discomfort, requires a radiologist or another professional specialized in breast diagnostics to perform the procedure shortly before surgery, and 15–20% of patients need a second surgery to completely remove the tumor. Therefore, new techniques have been developed but most of them have not yet been examined in large, prospective, multicenter studies. In this review, we discuss all available techniques and present the MELODY study that will investigate their safety, with a focus on patient, surgeon, and radiologist preference. Background: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. Methods: We performed a systematic review on localization techniques for non-palpable breast cancer. Results: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons' and radiologists' attitudes towards these techniques. Conclusions: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies. [ABSTRACT FROM AUTHOR]

Introduction: Contralateral axillary lymph node metastasis (CALNM) in breast cancer (BC) is considered a distant metastasis, marking stage 4cancer. Therefore, it is generally treated as an incurable disease. However, in clinical practice, staging and treatment remain controversial due to a paucity of data, and the St. Gallen 2021 consensus panel recommended a curative approach in patients with oligometastatic disease. Aberrant lymph node (LN) drainage following previous surgery or radiotherapy is common. Therefore, CALNM may be considered a regional event rather than systemic disease, and a re-sentinel procedure aided by lymphoscintigraphy permits adequate regional staging. Case report: Here, we report a 37-year-old patient with Lynch syndrome who presented with CALNM in an ipsilateral relapse of a moderately differentiated invasive ductal BC (ER 90%, PR 30%, HER2 negative, Ki-67 25%, microsatellite stable), 3 years after the initial diagnosis. Lymphoscintigraphy detected a positive sentinel LN in the contralateral axilla despite no sign of LN involvement or distant metastases on FDG PET/CT or MRI. The patient underwent bilateral mastectomy with sentinel node dissection, surgical reconstruction with histological confirmation of the CALNM, left axillary dissection, adjuvant chemotherapy, and anti-hormone therapy. In addition to her regular BC follow-up visits, the patient will undergo annual colonoscopy, gastroscopy, abdominal, and vaginal ultrasound screening. In January 2023, the patient was free of progression for 23 months after initiation of treatment for recurrent BC and CALNM. Conclusion: This case highlights the value of delayed lymphoscintigraphy and the contribution of sentinel procedure for local control in the setting of recurrent BC. Aberrant lymph node drainage following previous surgery may be the underlying cause of CALNM. We propose that CALNM without evidence of systemic metastasis should be considered a regional event in recurrent BC, and thus, a curative approach can be pursued. The next AJCC BC staging should clarify the role of CALNM in recurrent BC to allow for the development of specific treatment guidelines. [ABSTRACT FROM AUTHOR]

The American Society of Breast Surgeons (ASBrS) recently classified oncoplastic breast conserving surgery (OBCS) into two levels. The association of resection ratio during OBCS with patient-reported outcomes (PRO) is unclear. Patients with stage 0-III breast cancer undergoing OBCS between 01/2011-04/2023 at a Swiss university hospital, who completed at least one postoperative BREAST-Q PRO questionnaire were identified from a prospectively maintained institutional database. Outcomes included differences in PROs between patients after ASBrS level I (<20 % of breast tissue removed) versus level II surgery (20–50 %). Of 202 eligible patients, 129 (63.9 %) underwent level I OBCS, and 73 (36.1 %) level II. Six patients (3.0 %) who underwent completion mastectomy were excluded. The median time to final PROs was 25.4 months. Patients undergoing ASBrS level II surgery were more frequently affected by delayed wound healing (p < 0.001). ASBrS level was not found to independently predict any BreastQ domain. However, delayed wound healing was shown to reduce short-term physical well-being (estimated difference −26.27, 95 % confidence interval [CI] −39.33 to −13.22, p < 0.001). Higher age was associated with improved PROs. ASBrS level II surgery allows the removal of larger tumors without impairing PROs. Preventive measures for delayed wound healing and close postoperative follow-up to promptly treat wound healing disorders may avoid short-term reductions in physical well-being. • High-volume oncoplastic breast conserving surgery allows removal of larger tumors. • High-volume oncoplastic surgery does not impair patient-reported outcomes. • Delayed wound healing impairs short-term physical well-being. [ABSTRACT FROM AUTHOR]

Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR • Autologous breast reconstruction is increasingly preferred over implants in the setting of radiation therapy. • Use of patient-reported outcomes is endorsed. • Shape and size of reconstructed breasts can hinder radiotherapy planning. • There is a need for randomised phase III trials. [ABSTRACT FROM AUTHOR]

Long-term follow-up data from multicenter phase III non-inferiority trials confirmed the safety of omission of axillary dissection in selected patients with clinically node-negative, sentinel node-positive breast cancer. Several ongoing trials investigate extended eligibility of the Z0011 protocol in the adjuvant setting. De-escalation of axillary surgery in patients with clinically node-positive breast cancer is currently limited to the neoadjuvant setting, where the sentinel procedure is used to determine nodal pathological complete response. Targeted axillary dissection lowers the false-negative rate of the sentinel procedure, which, however, is consistently associated with a very low risk of axillary recurrence in several recent single-center series. Axillary dissection remains standard care in patients with residual disease after neoadjuvant chemotherapy while the results of Alliance A011202 are pending. The TAXIS trial investigates the role of tailored axillary surgery in patients with clinically node-positive breast cancer, a novel concept designed to selectively remove positive nodes in the adjuvant and neoadjuvant setting. • Current indications for performing axillary lymph node dissection. • De-escalating axillary surgery strategies in node-positive breast cancer. • New concept for clinically node-positive breast cancer. [ABSTRACT FROM AUTHOR]

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. 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. 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%. TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND. • 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 [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to compare the risk of complications and recurrence between oncoplastic and conventional breast surgery. Methods: This is a retrospective analysis of a consecutive series of 436 patients with stage I–III breast cancer who underwent surgery at the University Hospital of Basel between 2011 and 2018. Results: The nipple/skin-sparing mastectomy (NSM/SSM) group showed significantly more delayed wound healing (32.7 vs. 5.8%, p < 0.001) and skin necrosis (13.9 vs. 1.9%, p = 0.020) compared to conventional mastectomy (CM), which corresponded to significantly higher odds of short-term complications (OR 2.34, 95% CI 1.02–5.35, p = 0.044). The incidence rate of long-term morbidity in oncoplastic breast-conserving surgery (OBCS) was significantly higher compared to conventional breast-conserving surgery (CBCS; 25.5 vs. 11.3 per 100 patient years [PY], p < 0.001), in particular concerning chronic pain (13.3 vs. 6.6, p = 0.011) and lymphedema (4.1 vs. 0.4, p = 0.003). Seroma as a long-term morbidity occurred more often in the CM group compared to the NSM/SSM group (5.8 vs. 0.5 per 100 PY, p = 0.004). Patients received adjuvant treatment earlier after CM compared to NSM/SSM (HR 1.83, 95% CI 1.05–3.19, p = 0.034). There were no significant differences in the incidence of positive margins nor in the odds of recurrence after OBCS versus CBCS and after NSM/SSM versus CM. Conclusions: Even though the present study confirmed expected differences in complications and morbidity, it suggested that oncoplastic surgery is oncologically safe. Patients undergoing NSM/SSM should be followed closely to allow early detection and treatment of frequently associated complications and ensure timely start of adjuvant therapy. [ABSTRACT FROM AUTHOR]

The therapeutic role of axillary dissection in breast cancer is gradually abandoned. However, in some cases axillary dissection is still indicated, and this mandates expertise in planning the operation according to imaging, understanding of current methods of axillary marking, and expertise in performing a more radical resection. In this comment we describe cases of gross nodal disease that was left behind at the time of axillary dissection and was later noted on a radiation planning CT. [ABSTRACT FROM AUTHOR]

One of the most important news occurring in axillary surgery since the last St. Gallen Conference in 2017 was the publication of confirmatory long-term follow-up data from several large multicenter phase III non-inferiority trials, which clearly showed that axillary dissection can no longer be considered standard practice in all node-positive patients. Several groups are currently investigating the most accurate method to reliably determine axillary pathologic complete response after neoadjuvant chemotherapy to omit axillary dissection in initially clinically node-positive patients. Concerning breast surgery, after publication of the broadly endorsed definition of "no ink on tumor" for negative margins, many groups have demonstrated the expected decrease in re-excision rates. More evidence is needed to evaluate the adequate margin width in the neoadjuvant setting, where an increased risk of local recurrence has been shown compared to the upfront surgery setting. Besides narrowing margins and local down-staging by neoadjuvant therapy, another potential way to increase breast conservation rates is eliminating multicentricity as a contraindication. This requires high-volume tumorectomy, which has been demonstrated to be oncologically safe in a large series of oncoplastic reduction mammoplasties. However, the beneficial impact of oncoplastic surgery on quality of life still needs to be confirmed. The Oncoplastic Breast Consortium (OPBC) is a rapidly growing global non-profit organization that is committed to identifying and prioritizing knowledge gaps in this field. Currently, the OPBC focuses on research projects that address the major heterogeneity in breast reconstruction practice after nipple-sparing mastectomy. [ABSTRACT FROM AUTHOR]

Oncoplastic breast conserving surgery (OBCS) aims to provide safe and satisfying surgery for breast cancer patients. The American Society of Breast Surgeons (ASBrS) classification system is based on volumetric displacement cut-offs (level I for <20% of breast volume; level II for 20–50%). It aims to facilitate communication among treating physicians and patients. Here, we investigate whether the extent of OBCS as classified by ASBrS independently predicts postoperative complications. This retrospective analysis of a prospectively maintained database included patients with stage I–III breast cancer who underwent OBCS between 03/2011 and 12/2020 at a Swiss university hospital. Outcomes included short-term (≤30 days) complications and chronic (>30 days) pain after surgery. Multivariate logistic regression models were used to identify independent predictors. In total, 439 patients were included, 314 (71.5%) received ASBrS level I surgery, and 125 (28.5%) underwent ASBrS level II surgery. ASBrS level II was found to be an independent predictor of delayed wound healing (odds ratio [OR] 9.75, 95% confidence intervals (CI) 2.96–32.10). However, ASBrS level did not predict chronic postoperative pain (incidence rate ratio [IRR] 1.20, 95%CI 0.85–1.70), as opposed to age (IRR 1.19, 95%CI 1.11–1.27 per 5 years decrease), and weight disorders (underweight [BMI <18.5] vs. normal weight [BMI 18.5 < 25]: IRR 4.02, 95%CI 1.70–9.54; obese [BMI ≥30] vs. normal weight: IRR 2.07, 95%CI 1.37–3.13). ASBrS level II surgery predicted delayed wound healing, warranting close clinical follow-up and prompt treatment to avoid delays in adjuvant therapy. • ASBrS level independently predicts delayed wound healing • Overall, ASBrS level did not predict short-term complications • ASBrS level did not predict chronic pain after surgery [ABSTRACT FROM AUTHOR]

• The OPBC and EUBREAST ranked 51 important questions in axillary management. • Guidelines should be developed for axillary imaging and de-escalation of surgery. • Research was recommended for de-escalation of radiotherapy. • Management of residual nodal disease after surgery remains unclear. The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register. [ABSTRACT FROM AUTHOR]

Axillary lymph node dissection (ALND) has been standard of care for all patients with breast cancer until the 1990s. The stepwise retreat of breast surgeons from the axilla began after the introduction of the sentinel lymph node procedure. The evidence based clinical trend toward the omission of ALND has advanced to include patients with affected nodes, and several ongoing randomized controlled trials are evaluating the remaining indications for ALND. Conflicting with this trend toward less axillary surgery, indication and extent of regional nodal irradiation are currently broadened, equally supported by evidence from randomized trials. The present review summarizes this conflicting evidence, presents ongoing trials, and discusses the current and future optimal regional management of patients with affected nodes. [ABSTRACT FROM AUTHOR]

Aim s Src homology phosphotyrosyl phosphatase-2 (SHP2) is a ubiquitously expressed phosphatase that plays an essential role in the downstream signalling pathways of multiple growth factor receptors, thus representing a potential target for cancer therapy. Recent studies suggest that SHP2 contributes to tumour initiation, progression and metastasis in breast cancer, yet the impact of SHP2 expression on prognosis in human breast cancer has not been evaluated. Methods and results To explore further the role of SHP2 in breast cancer, we conducted an immunohistochemical study using a tissue microarray encompassing 1401 formalin-fixed breast cancer specimens with detailed clinical annotation and outcome data. Of 1401 evaluable breast cancers, 651 (46%) were positive for SHP2. SHP2 expression was associated positively with tumour grade, lymph node status and tumour stage. In univariate survival analysis, cases with SHP2 expression had a significantly worse overall survival (OS). In multivariate analysis, SHP2 remained an independent negative prognostic factor for OS. SHP2 expression was a negative prognostic factor for OS in the luminal A and the luminal B HER2− intrinsic subtypes. Conclusions Our data demonstrate for the first time that SHP2 is an independent predictor of survival in breast cancer, suggesting that SHP2 may be a potential target for therapy. [ABSTRACT FROM AUTHOR]

Whereas specimen radiography (SR) is an established strategy for intraoperative resection margin analysis during breast-conserving surgery for nonpalpable lesions, the use of frozen section analysis (FSA) is still a matter of debate. A retrospective review was conducted of 115 consecutive operations in which the two objectives sought were the excision of nonpalpable malignant lesions and breast conservation. Breast surgery was performed in the Gynecology and the Surgery Departments at the Basel University Hospital Breast Center. Whereas one department preferably uses SR for intraoperative margin assessments of lesions involving ductal carcinoma in situ (DCIS) or atypical ductal hyperplasia, the other uses FSA to increase the rate of complete removal of these lesions with a single procedure. The respective accuracy and therapeutic impact of these two techniques are compared here. Intraoperative resection margin assessments were performed with FSA in 80 and SR in 35 of a total of 115 operations performed on 111 patients with pTis, pT1, or pT2 nonpalpable breast cancer. FSA diagnostic accuracy, sensitivity, and specificity were 83.8%, 80.0%, and 87.5%, respectively, compared to 60%, 60%, and 60%, respectively, for SR. FSA tended to have a stronger therapeutic impact than SR in terms of the number of patients in whom initially positive margins were rendered margin-negative thanks to intraoperative analysis and immediate reexcision or mastectomy (27.5% vs. 14.3%; p = 0.124). More importantly, significantly fewer secondary reexcisions were performed in the FSA series than in the SR series (12.5% vs. 37.1%; p = 0.002). Finally, the intraoperative detection of invasive cancer with FSA led to a significantly lower number of secondary procedures for axillary lymph node staging (5% vs. 25.7%; p = 0.001). The present results suggest that FSA may be more accurate than SR for analyzing intraoperative resection margins during breast-conserving surgery for nonpalpable lesions. [ABSTRACT FROM AUTHOR]

Objective: To assess the potential of advanced breast biopsy instrumentation (ABBI) to clarify the diagnosis of impalpable mammographic lesions and to remove the entire malignant lesions with clear margins. Design: Prospective assessment in a consecutive series of patients. Setting: University hospital, Basel, Switzerland. Subjects: 139 patients presenting with144 impalpable microcalcifications or solid nodular densities evident on screening and follow-up mammograms that were suspicious of malignancy. Main outcome measures: Feasibility, sensitivity, efficiency in obtaining definitive diagnoses in an outpatient clinic under local anaesthesia, feasibility of complete removal of a primary malignancy, and intervention-related morbidity. Results: The ABBI procedure was successful in 135/144 (94%); an accurate diagnosis was made in 129/130 patients followed up (99%), sensitivity for malignant lesions was 31/32 (97%) and there were 2 complications (2%). Margins of the biopsy cylinder contained a malignant lesion in 26/31 (84%). Conclusions: Excisional biopsy using the ABBI system is a reliable diagnostic tool with a low morbidity. As in other published series margins were often not clear of tumour and therefore the therapeutic use of the ABBI procedure is limited. [ABSTRACT FROM AUTHOR]

Oncoplastic breast conserving surgery is increasingly used to treat patients with breast cancer. In the absence of randomized data, a large body of observational evidence consistently indicates low rates of recurrence and high rates of survival, but points to a higher rate of complications compared to conventional breast conserving surgery. Established goals of oncoplastic breast conserving surgery are to broaden the indication for breast conservation towards larger tumors, and to improve esthetic outcomes. The benefit from the patient's perspective, however, remains largely to be confirmed. There is a growing demand to standardize various aspects of oncoplastic breast conserving surgery for implementation in clinical research and practice. Several classification systems and outcomes measurement tools have been proposed, but to the present day, none of them has achieved international acceptance. [ABSTRACT FROM AUTHOR]

Interaction between cancerous, non-transformed cells, and non-cellular components within the tumor microenvironment plays a key role in response to treatment. However, short-term culture or xenotransplantation of cancer specimens in immunodeficient animals results in dramatic modifications of the tumor microenvironment, thus preventing reliable assessment of compounds or biologicals of potential therapeutic relevance. We used a perfusion-based bioreactor developed for tissue engineering purposes to successfully maintain the tumor microenvironment of freshly excised breast cancer tissue obtained from 27 breast cancer patients and used this platform to test the therapeutic effect of antiestrogens as well as checkpoint-inhibitors on the cancer cells. Viability and functions of tumor and immune cells could be maintained for over 2 weeks in perfused bioreactors. Next generation sequencing authenticated cultured tissue specimens as closely matching the original clinical samples. Anti-estrogen treatment of cultured estrogen receptor positive breast cancer tissue as well as administration of pertuzumab to a Her2 positive breast cancer both had an anti-proliferative effect. Treatment with anti-programmed-death-Ligand (PD-L)-1 and anti-cytotoxic T lymphocyte-associated protein (CTLA)-4 antibodies lead to immune activation, evidenced by increased lymphocyte proliferation, increased expression of IFNγ, and decreased expression of IL10, accompanied by a massive cancer cell death inex vivotriple negative breast cancer specimens. In the era of personalized medicine, theex vivoculture of breast cancer tissue represents a promising approach for the pre-clinical evaluation of conventional and immune-mediated treatments and provides a platform for testing of innovative treatments. [ABSTRACT FROM PUBLISHER]

Neoadjuvant systemic treatment elicits a pathologic complete response (pCR) in about 35% of women with breast cancer. In such cases, breast surgery may be considered overtreatment. We evaluated multivariate algorithms using patient, tumor, and vacuum-assisted biopsy (VAB) variables to identify patients with breast pCR. We developed and tested four multivariate algorithms: a logistic regression with elastic net penalty, an Extreme Gradient Boosting (XGBoost) tree, Support Vector Machines (SVM), and neural network. We used data from 457 women, randomly partitioned into training and test set (2:1), enrolled in three trials with stage 1–3 breast cancer, undergoing VAB before surgery. False-negative rate (FNR) and specificity were the main outcome measures. The best performing algorithm was validated in an independent fourth trial. In the test set (n = 152), the logistic regression with elastic net penalty, XGboost tree, SVM, and neural network revealed an FNR of 1.2% (1 of 85 patients with missed residual cancer). Specificity of the logistic regression with elastic net penalty was 52.2% (35 of 67 women with surgically confirmed breast pCR identified), of the XGBoost tree 55.2% (37 of 67), of SVM 62.7% (42 of 67), and of the neural network 67.2% (45 of 67). External validation (n = 50) of the neural network showed an FNR of 0% (0 of 27) and a specificity of 65.2% (15 of 23). Area under the ROC curve for the neural network was 0.97 (95% CI, 0.94–1.00). A multivariate algorithm can accurately select breast cancer patients without residual cancer after neoadjuvant treatment. • Identify women with a complete response in the breast after neoadjuvant treatment. • We compared the diagnostic performance of multivariate algorithms to breast surgery. • An international cohort of 457 women was used for the algorithm development. • Upon validation (n = 50) the neural network missed 0% cancer compared to surgery. • Omitting breast cancer surgery for these women may be evaluated in future trials. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease. Tumor cells and associated healthy cells form ecosystems that determine disease progression and response to therapy. To characterize features of breast cancer ecosystems and their associations with clinical data, we analyzed 144 human breast tumor and 50 non-tumor tissue samples using mass cytometry. The expression of 73 proteins in 26 million cells was evaluated using tumor and immune cell-centric antibody panels. Tumors displayed individuality in tumor cell composition, including phenotypic abnormalities and phenotype dominance. Relationship analyses between tumor and immune cells revealed characteristics of ecosystems related to immunosuppression and poor prognosis. High frequencies of PD-L1+ tumor-associated macrophages and exhausted T cells were found in high-grade ER+ and ER− tumors. This large-scale, single-cell atlas deepens our understanding of breast tumor ecosystems and suggests that ecosystem-based patient classification will facilitate identification of individuals for precision medicine approaches targeting the tumor and its immunoenvironment. • Single-cell proteomics reveals tumor and immune cell diversity in tumor ecosystems • Breast cancer exhibits tumor cell phenotypic abnormalities and tumor individuality • PD-L1+ TAMs and exhausted T cells are abundant in high-grade ER− and ER+ tumors • Tumor-immune relationships in the tumor ecosystem are patient-stratifying A single-cell atlas of cancer and immune cells reveals distinct tumor ecosystems across breast cancer patients, informing prognosis and, potentially, therapy selection. [ABSTRACT FROM AUTHOR]