The impact of delayed wound healing on patient-reported outcomes after breast cancer surgery.

PURPOSE: Postoperative complications after breast cancer surgery may be associated with decreased quality of life. It remains unclear whether oncoplastic breast-conserving surgery or mastectomy with reconstruction lead to more postoperative complications than conventional breast surgery (CBS). As delayed wound healing (DWH) is one of the most frequent minor complications, we sought to investigate the significance of DWH for patient-reported outcomes after oncoplastic, reconstructive, and CBS. METHODS: Our study is a retrospective cohort study of consecutive patients with stage I-II breast cancer who underwent oncoplastic or CBS performed by three breast surgeons at a single tertiary referral hospital from June 2011 until May 2019. Patient-reported outcomes were evaluated postoperatively using the BREAST-Q questionnaire. Comparisons were made between patients with and without DWH. RESULTS: A total of 229 patients who met the inclusion criteria and 28 (12%) of them developed DWH, 27/158 (17%) in the oncoplastic breast-conserving surgery and reconstruction group and 1/71 (1%) in the CBS group. The mean time from surgery to BREAST-Q assessment was comparable in both groups (29 months in the DWH vs. 33 months in the normal wound healing group). No statistically significant difference for any BREAST-Q scale was detected between patients with and without DWH. This includes physical (p = 0.183), psychosocial (p = 0.489), sexual well-being (p = 0.895), and satisfaction with breasts (p = 0.068). CONCLUSION: Our study confirms that oncoplastic breast-conserving surgery and mastectomy with reconstruction lead to significantly more DWH than CBS. However, neither quality of life nor patient-reported outcomes following state-of-the-art reconstructive or oncoplastic breast-conserving surgery at a specialized center seem to be compromised.

Comparison of patient-reported outcomes among different types of oncoplastic breast surgery procedures.

BACKGROUND: This study aims to compare patient-reported outcomes (PROs) after different types of oncoplastic surgery (OPS) procedures and correlate the results with previously 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, psychosocial, and sexual well-being. Compared to normative data of healthy women, all OPS groups postoperatively achieved significantly better satisfaction with breasts, psychosocial, and sexual well-being. CONCLUSION: This study shows high PROs across all types of OPS, which were superior to normative data from healthy women. Our findings confirm that OPS is associated with high quality of life and patient satisfaction.

Retrospective, Multicenter Analysis Comparing Conventional with Oncoplastic Breast Conserving Surgery: Oncological and Surgical Outcomes in Women with High-Risk Breast Cancer from the OPBC-01/iTOP2 Study.

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.

Impact of Oncoplastic Breast Surgery on Rate of Complications, Time to Adjuvant Treatment, and Risk of Recurrence.

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.

Detection of clustered circulating tumour cells in early breast cancer.

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.

Predictors of Nodal Pathological Complete Response in Asian Women with Stage II-III Node-Positive Breast Cancer.

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.

Breast conservation and axillary management after primary systemic therapy in patients with early-stage breast cancer: the Lucerne toolbox.

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.

Knowledge gaps in oncoplastic breast surgery.

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.

Identification of Somatic Mutations in Thirty-year-old Serum Cell-free DNA From Patients With Breast Cancer: A Feasibility Study.

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.

News in surgery of patients with early breast cancer.

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.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications 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. METHODS: The 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. RESULTS: Consensus 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. CONCLUSIONS: In 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.