Background: This study aims to compare patient-reported outcomes (PROs) after different types of oncoplastic surgery (OPS) procedures and correlate the results with previ-ously published normative data from women with no prior history of breast cancer (BC) and breast surgery.Methods: Cross-sectional study of patients with stage I-II BC undergoing a specific selection of OPS procedures from 04/2012 to 12/2018 by three breast surgeons at a single tertiary referral hospital in Switzerland. PROs were evaluated using the postoperative BREAST-Q questionnaire.Results: One hundred twenty-seven patients met the inclusion criteria and were surveyed. All OPS techniques achieved comparably elevated scores in satisfaction with breasts, psychoso-cial, and sexual well-being. Compared to normative data of healthy women, all OPS groups postoperatively achieved significantly better satisfaction with breasts, psychosocial, and sex-ual well-being. Conclusion: This study shows high PROs across all types of OPS, which were superior to norma-tive data from healthy women. Our findings confirm that OPS is associated with high quality of life and patient satisfaction.(c) 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Else-vier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Introduction Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). Methods Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. Results A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 (“ink on tumor”) in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. Conclusions Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.

Background: Neoadjuvant chemotherapy (NAC) is increasingly used to treat node-positive (N+) breast cancer. Predictors of nodal pathological complete response (pCR) in Asian women are poorly described and there is variety in the management of the axilla after NAC. We evaluated predictors of nodal pCR and axillary management in a cohort of Asian N+ patients. Methods: Consecutive biopsy-proven N+ breast cancer patients treated with NAC were identified from the Shanghai Ruijin Hospital in China. Axillary lymph node dissection was performed on all patients, irrespective of the nodal response to NAC. Results: A total of 323 patients were included. Nodal pCR was achieved in 105 patients (33%), 15% of HR+/HER2- tumors, 38% of HR+/HER2+ tumors, 49% of HR-/HER2+ tumors, and 42% of HR-/HER2-tumors (p < 0.001). Factors associated with nodal pCR were (1) receptor status (HR+/HER2- [referent]: OR 3.42, 95% CI 1.43-8.16, p = 0.006 for HR+/HER2+; OR 4.19, 95% CI 1.85-9.50, p = 0.001 for HR-/HER2+; and OR 2.94, 95% CI 1.11-7.74, p = 0.029 for HR-/HER2-), (2) breast pCR (no pCR [referent]: OR 15.22, 95% CI 6.29-36.79, p < 0.001), and (3) absence of lymphovascular invasion (LVI [referent]: OR 9.04, 95% CI 2.09-39.18, p = 0.003). Conclusion: This study confirmed expected predictors of nodal pCR in Asian women and the benefit of NAC in downstaging the axilla independently of ethnicity.

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.

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.

Circulating tumour cell (CTC) clusters have been proposed to be major players in the metastatic spread of breast cancer, particularly during advanced disease stages. Yet, it is unclear whether or not they manifest in early breast cancer, as their occurrence in patients with metastasis-free primary disease has not been thoroughly evaluated. In this study, exploiting nanostructured titanium oxide-coated slides for shear-free CTC identification, we detect clustered CTCs in the curative setting of multiple patients with early breast cancer prior to surgical treatment, highlighting their presence already at early disease stages. These results spotlight an important aspect of metastasis biology and the possibility to intervene with anti-cluster therapeutics already during the early manifestation of breast cancer.

INTRODUCTION:The aim of this study was to assess the feasibility of cell-free DNA (cfDNA) extraction and circulating tumor DNA sequencing in 30-year-old serum samples.MATERIALS AND METHODS:We evaluated serum samples from 52 patients with breast cancer, which were collected between 1983 and 1991, with correlating clinicopathologic data. cfDNA was extracted by using the QIAamp Circulating Nucleic Acid Extraction Kit (Qiagen). Of these 52 cfDNA samples, 10 were randomly selected and sequenced with the Oncomine Breast cfDNA Assay (A31183). In a second step, high-depth targeted sequencing of 15 additional cfDNA samples was performed using a custom Ampliseq Ion Torrent panel targeting breast cancer-related genes.RESULTS:cfDNA extraction was successful in 52 (100%) of 52 patients with a total concentration of 0.2 to 54 ng/uL. A total of 24 cancer-specific mutations were found in 22 (88%) of the 25 samples undergoing sequencing. Of the 52 patients, 32 (62%) had died from breast cancer after a median follow-up of 7.9 years (interquartile range, 3.7-15.5 years).CONCLUSION:The present study shows that current next generation sequencing technology is sufficiently robust and specific to analyze 30-year-old serum. Therefore, longitudinal studies can be designed with storage of serum samples over many years, thereby obviating the need for timely and continuous cfDNA extraction and sequencing. The samples can be pooled and processed at once with the most modern technology available at the end of the study, when accumulation of events allows correlation of clinical outcomes with adequate power.

The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of 63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these 15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of surgical morbidity should be further assessed.

Invasive breast tumors that lack the expression of hormone receptors and lack overexpression/amplification of the human epidermal growth factor receptor 2 are defined as triple-negative breast cancers (TNBC) and warrant adjuvant chemotherapy. With the exception of very small tumors or patients not fit to receive cytotoxic treatment, there is ample clinical evidence to conform to these guidelines. Although TNBC constitute a group of biologically heterogeneous tumors, they show early and increased relapse patterns [1.Lin N.U. Vanderplas A. Hughes M.E. et al.Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network.Cancer. 2012; 118: 5463-5472Crossref PubMed Scopus (392) Google Scholar]. Chemotherapy has been shown to lead to a high rate of complete responses when administered preoperatively and a clear-cut improvement in overall survival [2.Liedtke C. Mazouni C. Hess K.R. et al.Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer.J Clin Oncol. 2008; 26: 1275-1281Crossref PubMed Scopus (2082) Google Scholar]. The cooperating investigators from France (Institut Curie and - Gustave Roussy), Italy (European Institute of Oncology), and South Korea (Asan Medical Center) have pooled individual patient data from four chemotherapy-untreated TNBC cohorts (n = 518) and have retrospectively carried out a number of predefined analyses to investigate the independent effect of stromal lymphocyte infiltration (sTILs) on survival. As could be expected for a chemotherapy-naive cohort, the average age was slightly higher (64 years) than in current neoadjuvant TNBC cohorts, the rate of nodal metastasis was low (17.4%; only 5% had >3 positive nodes) and the average tumor size was just below 2 cm. The independent prognostic value of sTILS previously described in chemotherapy-treated cohorts was maintained in this selected group of patients: each 10% increment of lymphocyte infiltration decreased the relative risk by around 10% for all survival end points [invasive disease-free survival (DFS), distant DFS, and overall survival]. The reported values are not only consistent but also almost identical, with a prior pooled analysis of over 2000 patients from nine studies treated with anthracycline-based chemotherapy (either with or without taxanes). Strikingly, stage I patients with sTILS >30% showed distant recurrence point estimates at 5 years that are comparable to patients with identical anatomic stages and lymphocyte infiltration but treated with full doses of anthracycline- and taxane-based chemotherapy. Given these observations and the absolute excellent outcome (D-DFS 97%) means that absolute benefits of adjuvant chemotherapy appear very small [3.Loi S. Drubay D. Adams S. et al.Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers.J Clin Oncol. 2019; 37: 559-569Crossref PubMed Scopus (347) Google Scholar, 4.www.tilsinbreastcancer.org. (16 September 2019, date last accessed).Google Scholar]. These clinical findings are also intriguing from an immunological point of view. In broad terms, our thought models concerning the immunology of (especially hormone-receptor independent) breast cancer have adhered to the ‘three E’ theory [5.Schreiber R.D. Old L.J. Smyth M.J. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion.Science. 2011; 331: 1565-1570Crossref PubMed Scopus (4066) Google Scholar]. According to this model, premalignant/non-invasive lesions are detected and eliminated and small/undetected tumors are kept at an equilibrium via humoral and cellular immune mechanisms. Once tumors have reached sufficient size for conventional clinical diagnosis of cancer, they have escaped this immune control and now have a propensity to grow and disseminate. Prior work on lymphocyte infiltration in TNBC has rightfully contributed to the common hypothesis that adjuvant cytotoxic chemotherapy treatment for TNBC reinvigorates cellular immune mechanisms and shift the immune balance back to elimination. In this model, cytotoxic treatment synergizes with what has been shown to be a predominantly T-cell infiltrate [6.Savas P. Virassamy B. Ye C. et al.Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis.Nat Med. 2018; 24: 986-993Crossref PubMed Scopus (465) Google Scholar] and enables profound immune responses that contribute to tumor shrinkage [7.Denkert C. von Minckwitz G. Darb-Esfahani S. et al.Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy.Lancet Oncol. 2018; 19: 40-50Abstract Full Text Full Text PDF PubMed Scopus (916) Google Scholar] and long DFS [3.Loi S. Drubay D. Adams S. et al.Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers.J Clin Oncol. 2019; 37: 559-569Crossref PubMed Scopus (347) Google Scholar]. The study from Park et al. [8.Park J.H. Jonas S.F. Bataillon G. et al.Prognostic value of tumorinfiltrating lymphocytes in patients with early-stage triple-negative breast cancers (TNBC) who did not receive adjuvant chemotherapy.Ann Oncol. 2019; 30: 1941-1949Abstract Full Text Full Text PDF PubMed Scopus (103) Google Scholar] questions the paradigm of ‘tipping the immunologic response’, in fact, the 518 patients analyzed in this study had identical rates of lymphocyte infiltration but did not receive chemotherapy. This report raises, therefore, the hypothesis that tumors in early stages with predominant lymphocyte infiltration may generate sufficient T-cell memory to maintain long disease-free intervals. This is achieved by simply surgically removing the tumor (with or without radiotherapy) in the absence of adjuvant chemotherapy. The data also raise questions concerning the type of immune infiltrate. Currently, there is sufficient clinical evidence to establish quantitative thresholds of stromal lymphocyte infiltration with good (>30%) analytic and clinical validity in terms of prediction of survival. However, there is little clinical evidence concerning prognosis in relation to the quality of the lymphocytic infiltrate. Savas et al. [6.Savas P. Virassamy B. Ye C. et al.Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis.Nat Med. 2018; 24: 986-993Crossref PubMed Scopus (465) Google Scholar] showed that tumors with elevated numbers of TILs contained CD8+ T cells with features of tissue-resident memory T-cell (TRM) differentiation, which expressed high levels of immune checkpoint molecules. Further similar research is likely to improve our understanding and deliver improved biomarkers. These data also have several implications for future clinical trials in TNBC. Currently, multiple combinations of chemotherapy with new agents are being investigated in the neoadjuvant setting. Especially in the case of immuno-oncology, but also for synthetic lethality approaches, these combinations will increase drug (and financial) toxicity. It is, therefore, important that the validity of these trials is not compromised by the inclusion of cases that may already be exquisitely sensitive to standard chemotherapy or may not need cytotoxic treatment at all. Clinical trial development that focuses on the post-neoadjuvant setting, on the other hand, has the potential of targeting resistant tumors rather than those with good and early responses. Furthermore, recent consensus guidelines have suggested the de-escalation of therapy in single-arm studies that prove adequate oncologic outcome [9.Burstein H.J. Curigliano G. Loibl S. et al.Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019.Ann Oncol. 2019; 30: 1541-1557Abstract Full Text Full Text PDF PubMed Scopus (350) Google Scholar]: There are three possible definitions of patients entering such a trial (Figure 1). First, the definition of stage I/lymphocyte predominant TNBC creates a strong rationale to prospectively investigate the outcome of patients in the absence of (or considerably less) chemotherapy. In addition, it is increasingly likely that additional molecular classification, including gene-expression studies in combination with low anatomic stages, may further identify additional good prognosis subsets of TNBC [10.Garrido-Castro A.C. Lin N.U. Polyak K. Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment.Cancer Discov. 2019; 9: 176-198Crossref PubMed Scopus (489) Google Scholar]. Finally, TNBC can respond rapidly to chemotherapy and multiparametric magnetic resonance imaging can reliably predict response and survival as early as the second cycle of chemotherapy [11.Tahmassebi A. Wengert G.J. Helbich T.H. et al.Impact of machine learning with multiparametric magnetic resonance imaging of the breast for early prediction of response to neoadjuvant chemotherapy and survival outcomes in breast cancer patients.Invest Radiol. 2019; 54: 110-117Crossref PubMed Scopus (127) Google Scholar]. In this scenario, patients would stop cytotoxic treatment after only a few cycles of chemotherapy and receive no further systemic treatment if surgery proves excellent response. TILs as a biomarker have been under intense scrutiny due to their lack of clinical utility concerning treatment decisions. The presented evidence now suggests that this biomarker has the potential to identify patients for chemotherapy and immunotherapy de-escalation studies: Perhaps we could bring fewer owls to Athens. None declared.

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.

Background: The implementation of breast cancer (BC) screening programs and diagnostics have resulted in up to 35% of BC being clinically non-palpable at diagnosis1. In our breastcenter we recently switched from wire-guided localization (WGL) to radioguided seed localization (RLS) for the localization of non-palpable tumors. RSL involves a small titanium seed (4 x 0.8mm), which is labeled with I-125 and introduced into the lesion percutaneously. The seed is then localized intraoperatively with a gamma probe. A recent meta-analysis who compared RSL vs. WGL has shown a lower rate of involved margins, a lower reoperation rate and a shorter surgical operative time with RSL but no difference in the volume of the specimens removed between the two groups2. RLS can also be used prior to systemic treatment to mark pathological lymphnodes in order to perform targeted axilla dissection and to localize non-palpable lymphnodes. We aim to describe our experience in introducing RLS in our breast center and to compare the above mentioned variables among two comparable groups.

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