Omission of breast surgery in selected breast cancer patients with excellent response to neoadjuvant systemic therapy.

Modern neoadjuvant systemic therapy (NST) can result in high pathologic complete response rates (pCR) in triple negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) breast cancer. The role of surgery is, therefore, being reconsidered in this rapidly evolving field. This report presents oncological outcomes of seven patients with TN or HER2+ breast cancer, with exceptional response to NST, and a post-NST image-guided vacuum assisted biopsy showing no residual disease (ypT0), who opted not to have breast surgery. The median age was 49 (IQR 36-61) years and the median tumour size at diagnosis was 50 (IQR 16-65) mm. All patients received breast radiotherapy and continued adjuvant systemic therapies as appropriate. At a median follow-up of 67 (IQR 61-77) months, all patients were alive and free of disease. This small case series supports the need for further research in 'exceptional responders' to provide safe, individualized patient-centred care.

Omission of Breast Surgery in Exceptional Responders.

Breast cancer management has transformed significantly over the last decades, primarily through the integration of neoadjuvant systemic therapy (NST) and the evolving understanding of tumor biology, enabling more tailored treatment strategies. The aim of this review is to critically present the historical context and contemporary evidence surrounding the potential of omission of surgery post-NST, focusing on exceptional responders who have achieved a pathologic complete response (pCR). Identifying these exceptional responders before surgery remains a challenge, however standardized image-guided biopsy may allow optimized patient selection. The safety and feasibility of omitting breast and axillary surgeries in these exceptional responders are explored in ongoing clinical trials and the reported preliminary results appear promising. Moreover, understanding patient and physician perspectives regarding the potential elimination of surgery post-NST is integral. While some patients express a preference to omit or minimize surgery, the majority of healthcare providers are intrigued by the prospect of avoiding surgical interventions and endorse further research in this field.

Oncological Outcomes After Multidisciplinary Management of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon type of non-Hodgkin lymphoma, associated with breast implant capsules. Despite improvements in our understanding of BIA-ALCL, communicating the prognosis to patients remains challenging due to limited long-term follow-up data. This has important implications for decision-making, including recommendations for subsequent reconstructive procedures. The aim of this study was to assess the longer-term oncological outcomes of patients receiving multidisciplinary treatment for BIA-ALCL. METHODS: This was a retrospective cohort study of BIA-ALCL patients treated at a tertiary referral unit. The data are presented using simple descriptive statistics. RESULTS: Between 2015 and 2022, 18 BIA-ALCL patients were treated at our institution. The median age at diagnosis was 48.5 (IQR 41-55) years. Ten patients developed BIA-ALCL after cosmetic breast augmentation, and 8 after breast reconstruction following mastectomy for cancer. All patients had a history of textured implant insertion. The median time from first implant surgery to diagnosis was 8.5 (IQR 7-12) years. All patients underwent en-bloc total capsulectomy with implant removal, and 2 received systemic therapy. Fifteen patients had Stage I (IA-IC) disease, 2 had Stage IIA and 1 Stage III BIA-ALCL, based on the TNM classification system. At a median follow-up of 45 (IQR 15-71) months, there were no episodes of local or systemic relapse or death. CONCLUSIONS: Surgical management for BIA-ALCL is sufficient in early-stage disease, and associated with excellent oncological outcomes. This information is reassuring for patients when discussing recurrence risk.

Outcomes of Different Quality of Life Assessment Modalities After Breast Cancer Therapy: A Network Meta-analysis.

Importance: Improvement in clinical understanding of the priorities of patients with breast cancer (BC) regarding postoperative aesthetic outcomes (AOs) is needed. Objective: To assess expert panel and computerized evaluation modalities against patient-reported outcome measures (PROMs), the gold standard of AO assessment, in patients after surgical management of BC. Data Sources: Embase, MEDLINE, PsycINFO, PubMed, the Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov were interrogated from inception through August 5, 2022. Search terms included breast conserving AND aesthetic outcome AND breast cancer. Ten observational studies were eligible for inclusion, with the earliest date of database collection on December 15, 2022. Study Selection: Studies with at least 1 pairwise comparison (PROM vs expert panel or PROM vs computerized evaluation with Breast Cancer Conservation Treatment cosmetic results [BCCT.core] software) were considered eligible if they included patients who received BC treatment with curative intent. Studies reporting solely on risk reduction or benign surgical procedures were excluded to ensure transitivity. Data Extraction and Synthesis: Two independent reviewers extracted study data with an independent cross-check from a third reviewer. The quality of included observational studies was assessed using the Newcastle-Ottawa Scale, and the level of evidence quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. Confidence in network meta-analysis results was analyzed with the Confidence in Network Meta-analysis semiautomated tool. Effect size was reported using random-effects odds ratios (ORs) and cumulative ratios of ORs with 95% credibility intervals (CrIs). Main Outcomes and Measures: The primary outcome of this network meta-analysis was modality (expert panel or computer software) discordance from PROMs. Four-point Likert responses across PROMs, expert panel assessment, and BCCT.core evaluation of AOs were assessed. Results: A total of 10 observational studies including 3083 patients (median [IQR] age, 59 [50-60] years; median [range] follow-up, 39.0 [22.5-80.5] months) with reported AOs were assessed and homogenized in 4 distinct Likert response groups (excellent, very good, satisfactory, and bad). Overall network incoherence was low (χ22 = 0.35; P = .83). Overall, panel and software modalities graded AO outcomes worse than PROMs. Specifically, for excellent vs all other responses, the panel to PROM ratio of ORs was 0.30 (95% CrI, 0.17-0.53; I2 = 86%) and the BCCT.core to PROM ratio of ORs was 0.28 (95% CrI, 0.13-0.59; I2 = 95%), while the BCCT.core to panel ratio of ORs was 0.93 (95% CrI, 0.46-1.88; I2 = 88%). Conclusions and Relevance: In this study, patients scored AOs higher than both expert panels and computer software. Standardization and supplementation of expert panel and software AO tools with racially, ethnically, and culturally inclusive PROMs is needed to improve clinical evaluation of the journey of patients with BC and to prioritize components of therapeutic outcomes.

Evolution and refinement of magnetically guided sentinel lymph node detection in breast cancer: meta-analysis.

BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD). METHODS: A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach. RESULTS: In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI ± BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P = 0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI ± BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection. CONCLUSION: The performance of SPIO is comparable to that of RI ± BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated.

A Comparative Study of Secondary Procedures after Subpectoral and Prepectoral Single-Stage Implant-Based Breast Reconstruction.

BACKGROUND: Implant-based breast reconstruction (IBR) is the most commonly used procedure to reconstruct the breast after mastectomy. The advantages and disadvantages of subpectoral versus prepectoral implant placement remain a matter of debate. This study compares the need for secondary aesthetic procedures between prepectoral and subpectoral IBR. METHODS: This is a retrospective cohort study of consecutive patients who underwent subpectoral or prepectoral IBR between 2015 and 2018 under a single surgeon at a tertiary breast unit. The primary endpoint was the number of secondary procedures performed to improve the aesthetic outcome. Secondary endpoints included the number of secondary procedures during the first year. RESULTS: A total of 271 one-stage IBRs were performed (subpectoral, n = 128 in 74 patients; prepectoral, n = 143 in 84 patients). Overall, more patients required secondary procedures in the subpectoral group (36.5% versus 19%; P = 0.014), although through longer follow-up. The most common procedures were pocket revision and implant exchange [11.7% versus 3.5% ( P = 0.010); 11.7% versus 4.2% ( P = 0.021)], whereas fat grafting was similar between the two groups (46% versus 40.5%; P = 0.777). When adjusted for follow-up time, there was no significant difference in the number of secondary procedures undertaken in the subpectoral versus the prepectoral group (21% versus 16%, respectively; P = 0.288) at 1 year. CONCLUSIONS: The requirement for secondary procedures at 1 year was not different between groups. The need for fat grafting was not increased following prepectoral IBR. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

De-escalating Surgery Among Patients with HER2 + and Triple Negative Breast Cancer.

Purpose of Review: De-escalation of surgery has been central in the evolution of multidisciplinary management of breast cancer. Advances in oncology and increasing use of neoadjuvant chemotherapy (NACT) have opened opportunities for further surgical de-escalation especially for HER2 + and triple negative (TN) disease. The aim of this review is to discuss the recent data on de-escalation of surgery as well as the future directions. Recent Findings: Patients with TN and HER2 + breast cancer with excellent response to NACT would be the ideal candidates for surgical de-escalation. Post-NACT image-guided biopsy, potentially combined with machine learning algorithms, may accurately identify patients achieving pathologic complete response that would be eligible for clinical trials assessing safety of omission of breast and axillary surgery. Summary: Multidisciplinary research is required to further support results of preliminary studies. Current data point towards a future when even less or no surgery may be required for exceptional responders.

Satisfaction with Long-Term Aesthetic and 10 Years Oncologic Outcome following Risk-Reducing Mastectomy and Implant-Based Breast Reconstruction with or without Nipple Preservation.

Incidence of bilateral risk-reducing mastectomies (RRMs) is increasing. The aim of this study was to compare satisfaction, aesthetic and oncological outcomes in women undergoing RRM with implant-based reconstruction comparing nipple-sparing mastectomy (NSM) with skin-sparing mastectomy (SSM) (sacrificing the nipple +/− nipple reconstruction). Women who had undergone bilateral RRM between 1997 and 2016 were invited. Aesthetic outcome and nipple symmetry were evaluated using standardized anthropometric measurements. The oncological outcome was assessed at last documented follow up. Ninety-three women (186 breasts) participated, 60 (64.5%) had NSM, 33 (35.5%) SSM. Median time between surgery and participation was 98.4 months (IQR: 61.7−133.9). Of the women, 23/33 (69.7%) who had SSM underwent nipple reconstruction. Nipple projection was shorter in the reconstructed SSM group than the maintained NSM group (p < 0.001). There was no significant difference in overall symmetry (p = 0.670), satisfaction regarding nipple preservation (p = 0.257) or overall nipple satisfaction (p = 0.074). There were no diagnoses of breast cancer at a median follow up of 129 months (IQR: 65−160.6). Women who undergo nipple-sparing RRM maintain long-term nipple symmetry. Nipple projection was less maintained after nipple reconstruction. Although satisfaction with the nipples was higher in the NSM group, this did not reach statistical significance. No breast cancers developed after RRM with long-term follow up.

A Systematic Review and Meta-Analysis on the Role of Repeat Breast-Conserving Surgery for the Management of Ipsilateral Breast Cancer Recurrence.

INTRODUCTION: The standard surgical management of ipsilateral breast cancer recurrence (IBCR) in patients previously treated with breast-conserving surgery (BCS) and radiotherapy (RT) is mastectomy. Recent international guidelines provide conflicting recommendations. The aim of this study was to perform a systematic literature review and meta-analysis of the oncological outcomes in patients with IBCR treated with repeat BCS (rBCS). METHODS: The MEDLINE and EMBASE databases were searched for relevant English-language publications, with no date restrictions. All relevant studies providing sufficient data to assess oncological outcomes (second local recurrence [LR] and overall survival [OS]) of rBCS for the management of IBCR after previous BCS and RT were included (PROSPERO registration CRD42021286123). RESULTS: Forty-two observational studies met the criteria and were included in the analysis. The pooled second LR rate after rBCS was 15.7% (95% confidence interval [CI] 12.1-19.7), and 10.3% (95% CI 6.9-14.3) after salvage mastectomy. On meta-analysis of comparative studies (n = 17), the risk ratio (RR) for second LR following rBCS compared with mastectomy was 2.103 (95% CI 1.535-2.883; p < 0.001, I2 = 55.1%). Repeat RT had a protective effect (coefficient: - 0.317, 95% CI - 0.596 to - 0.038; p = 0.026, I2 = 40.4%) for second LR. Pooled 5-year OS was 86.8% (95% CI 83.4-90.0) and 79.8% (95% CI 74.7-84.5) for rBCS and salvage mastectomy, respectively. Meta-analysis of comparative studies (n = 20) showed a small OS benefit in favor of rBCS (RR 1.040, 95% CI 1.003-1.079; p = 0.032, I2 = 70.8%). Overall evidence certainty was very low. CONCLUSIONS: This meta-analysis suggests rBCS could be considered as an option for the management of IBCR in patients previously treated with BCS and RT. Shared decision making, appropriate patient selection, and individualized approach are important for optimal outcomes.

Physical Characteristics of SurgiMend Meshed Biological ADM in Immediate Prepectoral Implant Breast Reconstruction.

With increasing acceptance of prepectoral implant breast reconstruction, there has been a requirement for biological acellular dermal matrices with conformational properties, high tensile strength, and rapid integration. SurgiMendPRS Meshed is a biological acellular dermal matrix derived from fetal calf with these specific characteristics for prepectoral implant breast reconstruction. The aim of this study was to test the performance of this mesh by recreating its surgical use ex-vivo using a variety of implants in an effort to define its physical properties. The mesh is usually attached with a number of interrupted sutures to the implant periphery, the variable being at the inferior border, where it can be attached as a snug fit at the level of the inframammary crease ("tent" technique) or sewn behind the implant, cradling the lower pole ("hammock" technique). The results show mesh elasticity to stretch with increasing implant weight. When used as a "hammock," greater stretch was demonstrated compared with the "tent" technique, allowing greater degrees of ptosis to be achieved. The suture points demonstrated lines of tension that progress evenly over the anterior implant surface. The mesh performed better when used at maximum stretch, but should not be forcibly stretched over an implant as the lines of stress show uneven distribution of lines of tension. These data provide a structural basis on optimum clinical use of this acellular dermal matrix in prepectoral implant breast reconstruction.

Cost and clinical benefit of imaging surveillance after treatment for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

Recent UK guidelines recommend that surveillance imaging should not be offered to patients who have undergone treatment for breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) unless clinically indicated. The aim of this study was to explore the evolving practice at a tertiary referral unit and quantify the direct economic costs (DEC) associated with post-treatment BIA-ALCL routine radiological surveillance prior to adoption of the guidelines. Eleven patients were treated for BIA-ALCL between 2015 and 2020. At a median follow-up of 38 months (IQR 12-47) there were no local or distant relapses. Two patients did not have any radiological surveillance and 1 had follow-up elsewhere. The remaining 8 patients had a combination of positron emission tomography/computed tomography (PET/CT) (n = 10), CT (n = 2), breast ultrasound (n = 6), mammogram (n = 4) and breast magnetic resonance imaging (MRI) (n = 1) as routine imaging follow-up not guided by clinical concerns. Total cost of imaging was £10,396 (€12,257) with a median cost of £1953 (€2304) per patient [IQR £526-2029 (€621-2394)]. This cost could have been saved based on current guidelines recommending no routine surveillance for asymptomatic patients.

Pre-pectoral one-stage breast reconstruction with anterior biological acellular dermal matrix coverage.

BACKGROUND: Pre-pectoral implant breast reconstruction (IBR) is gaining popularity. Several techniques using different types of meshes and methods of placement have been described, but no method is currently considered standard. The aim of this study was to evaluate the outcomes of pre-pectoral IBR using acellular dermal matrix (ADM) for anterior implant cover. METHODS: Retrospective cohort study of consecutive patients who underwent pre-pectoral IBR between November 2016 to August 2018. Data on demographics, adjuvant therapies and operative technique was collected. Postoperative complications, length of hospital stay and secondary cosmetic procedures were recorded. Statistical analysis was performed using descriptive statistics, non-parametric tests and logistic regression. RESULTS: One hundred and eleven pre-pectoral IBR were performed in 65 patients. Median age was 41 [interquartile range (IQR), 35-51.5] years, and BMI 22 (IQR, 20.4-24.4) kg/m2. Therapeutic mastectomy was performed in 33 procedures with nipples preservation in 78 cases. The median mastectomy weight and implant volume was 360 (IQR, 220-533) gr, and 445 (IQR, 400-475) cc respectively. At a median follow-up of 18 (IQR, 12-22.5) months, 37 mastectomies had at least 1 complication, but only 12 required surgery. The implant loss rate was 4.5% (5 cases). Lipofilling as secondary procedure was performed in 10.8% of cases. Factors associated with post-operative complications on univariate analysis were nipple preservation (P=0.028), BMI (P=0.01) and implant volume (P=0.027) but these did not remain significant on multivariate analysis. CONCLUSIONS: Pre-pectoral IBR using ADM for anterior implant cover is associated with low complication and reconstructive failure rate. Patient selection and meticulous surgical technique are important for successful outcome.

Identification of breast cancer patients with pathologic complete response in the breast after neoadjuvant systemic treatment by an intelligent vacuum-assisted biopsy.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: A multivariate algorithm can accurately select breast cancer patients without residual cancer after neoadjuvant treatment.

Accuracy of Post-Neoadjuvant Chemotherapy Image-Guided Breast Biopsy to Predict Residual Cancer.

Importance: Image-guided breast biopsy of a residual imaging abnormality or tumor bed after neoadjuvant chemotherapy (NACT) is increasingly used to assess residual cancer, facilitate risk-adaptive surgery, and potentially identify exceptional responders in whom local therapy may be de-escalated. Objective: To further assess the accuracy of post-NACT image-guided biopsy to predict residual cancer in the breast. Design, Setting, and Participants: This diagnostic study analyzed multicenter patient-level data of patients with breast cancer who were treated with NACT and underwent image-guided biopsy before surgery at Royal Marsden Hospital in London, UK; Seoul National University Hospital in Seoul, South Korea; and MD Anderson Cancer Center in Houston, Texas. Data were analyzed from June to July 2019. Main Outcomes and Measures: Diagnostic accuracy of post-NACT image-guided biopsy. Final surgical pathology was used as reference standard. Results: Data from 166 women were analyzed. The median (range) age was 49 (25-76) years. The median (range) tumor size on pretreatment and posttreatment imaging was 33.5 (12-100) mm and 10 (0-100) mm, respectively. The overall pathologic complete response rate was 51.2% (n = 85) (16.1% [5 of 31] for hormone receptor-positive/ERBB2 (formerly HER2)-negative; 44.7% [21 of 47] for hormone receptor-positive/ERBB2-positive; 69% [20 of 29] for hormone receptor-negative/ERBB2-positive; and 66.1% [39 of 59] for triple negative). The majority (143 [86.1%]) underwent image-guided vacuum-assisted biopsy (VAB), and 23 had core-cut biopsy. The median (range) needle gauge was 10 (7-14), and the median (range) number of samples was 6 (2-18). When image-guided biopsy (VAB and core-cut biopsy) was representative (159 [95.8%]), the false-negative rate across the whole cohort was 18.7% (95% CI, 10.6%-29.3%). Subgroup analysis of patients with a complete/partial clinical response and residual imaging abnormality of 2 cm or smaller with at least 6 VABs taken (76 [45.8%]) demonstrated a false-negative rate of 3.2% (95% CI, 0.1%-16.7%), a negative predictive value of 97.4% (95% CI, 86.5%-99.9%), and an overall accuracy of 89.5% (95% CI, 80.3%-95.3%). Conclusions and Relevance: This large multicenter pooled data analysis suggests that a standardized protocol using image-guided VAB of a tumor bed measuring 2 cm or smaller with 6 or more representative samples allows reliable prediction of residual disease. These results could inform the design of de-escalation trials in NACT exceptional responders testing the safety of eliminating surgery.