The multicenter experience in the multidisciplinary Italian breast units: a review and update.

A breast unit is a multidisciplinary center specialized in the management of women with breast diseases, including breast cancer (BC). It represents a care path, passing from screening activities to diagnostic investigations, from surgery to the definition of the therapeutic strategy, from psychophysical rehabilitation to long-term checks (follow-up), and up to genetic counseling. Since 2006, following a resolution issued by the European Parliament to urge member states to activate multidisciplinary breast centers by 2016, work has been underway throughout Italy to improve the management of women with BC. In Italy, the State-Regions agreement was signed on 18 December 2014, sanctioning the establishment of breast units. These centers must adhere to specific quality criteria and requirements. In 2020, the experts of the EUSOMA group (European Society of Breast Cancer Specialists), in their latest document published, expanded the requirements of the breast units. Furthermore, Senonetwork was founded in 2012 with the aim of allowing BC to be treated in breast units that comply with European requirements to ensure equal treatment opportunities for all Italian women. Indeed, the available data indicate that the BC patient has a greater chance of better treatment in the breast units with a multidisciplinary team, thus increasing the survival rate with a better quality of life, compared to those managed in nonspecialized structures. The present review is a perspective on the current Italian reality of breast units, updated with the available literature and the most recent epidemiological data from Senonetwork and AgeNaS.

Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial.

Importance: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent. Objective: To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography. Design, Setting, and Participants: The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023. Intervention: Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group). Main Outcomes and Measures: The primary end point of the study was distant disease-free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations. Results: Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor-positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group. Conclusions and Relevance: In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan. Trial Registration: ClinicalTrials.gov Identifier: NCT02167490.

Robot-assisted Nipple Sparing Mastectomy: Recent Advancements and Ongoing Controversies.

Purpose of review: The purpose of this review is to summarize the recent technical advancements in RNSM, describe the ongoing teaching programs, and discuss the ongoing controversies. Recent findings: Robot-assisted nipple sparing mastectomy (RNSM) is the newest addition to the armamentarium of surgical techniques for patients who require a mastectomy. The potential benefits of using the da Vinci® Robotic Surgical System (Intuitive Surgical, Sunnyvale, CA) are the small 3D camera and lighting offering superior visualization, the Endowrist robotic instruments offering greater range of motion, and surgeon being at a seated position at the console rendering a more ergonomic operating position. Summary: RNSM can potentially help overcome the technical difficulties of performing a conventional NSM. Further studies are needed to elucidate the oncologic safety and cost-effectiveness of RNSM.

Controversies and strengths of robot-assisted mastectomy.

Nipple-sparing mastectomy (NSM) is used to improve cosmetic outcomes while maintaining oncological safety in patients with early breast cancer; however, NSM requires a higher level of skill and workload than mastectomy and is associated with long, visible scars. Robotic surgical systems reduce surgeon workload and facilitate precise surgery. Considering the increasing support of robot-assisted NSM (RNSM), this paper aims to discuss the current controversies based on the research findings reported thus far. There are four concerns regarding RNSM; increased cost, oncological outcomes, the level of experience and skill, and standardization. It should be noted that RNSM is not a surgery performed on all patients but rather a procedure performed on selected patients who meet specific indications. A large-scale randomized clinical trial comparing robotic and conventional NSM has recently begun in Korea; therefore, it is necessary to wait for these results for more insight into oncological outcomes. Although the level of experience and skill required for robotic mastectomy may not be easily achieved by all surgeons, the learning curve for RNSM appears manageable and can be overcome with appropriate training and practice. Training programs and standardization efforts will help improve the overall quality of RNSM. There are some advantages to RNSM. The robotic system provides improved precision and accuracy, helping remove breast tissue more effectively. RNSM has advantages such as smaller scars, less blood loss, and a lower rate of surgical complications. Patients who undergo RNSM report better quality of life.

Metaplastic breast cancer: an all-round multidisciplinary consensus.

Metaplastic breast cancer (MpBC) is a rare and aggressive histologic subtype of breast cancer (BC) characterized by the presence of at least two cellular types, commonly epithelial and mesenchymal components. Despite growing evidence that MpBC is a unique entity, it has long been treated as a variant of nonspecial type (NST) BC. MpBC typically shows the phenotype of triple-negative breast cancer (TNBC), but compared to NST-TNBC, it is a relatively chemorefractory tumor associated with worse outcomes. Therefore, there is an urgent need to develop management guidelines specifically for MpBC to improve the prognosis of patients with early MpBC. This expert consensus aims to guide diagnosis and standardize clinical management of early MpBC among treating physicians. We provide guidance on the challenging radiological and pathological diagnosis of MpBC. Evidence on the involvement of genetic predisposition in the development of MpBC is also explored. We emphasize the importance of a multidisciplinary approach for the treatment of patients with early MpBC. The optimal surgery and radiotherapy approach is presented, as well as the opportunity offered by novel therapeutic approaches to increase treatment response in this chemoresistant subtype. Appropriate management of patients with MpBC is critical to reduce the high risk of local and distant recurrence that characterizes this disease.

Local treatment in patients with hereditary breast cancer: decision-making process in low-, moderate-, high-penetrance pathogenic germline mutation carriers.

PURPOSE OF REVIEW: We summarize recent evidence regarding commonly tested breast cancer susceptibility genes and review indications derived from recently published guidelines regarding management of carriers affected by early breast cancer (BC). RECENT FINDINGS: Management of affected women with a known genetic predisposition to BC was matter of debate at the most relevant international conferences, such as St. Gallen International Consensus Conference and San Antonio Breast Cancer Symposium held both in 2021. At the same time, a joint Experts Panel from American Society of Clinical Oncology/American Society for Radiation Oncology/Society of Surgical Oncology (ASCO/ASTRO/SSO) convened to develop recommendations to support clinical decision-making in this specific setting and results about administration of new systemic therapies such as poly adenosine diphosphate-ribose polymerase (PARP) inhibitors became available. SUMMARY: Population of patients affected by BC and carriers of mutations in susceptibility genes is progressively increasing, but new mutations identified do not always have a clear clinical impact.To date, we have data to support consideration of different local management choices for affected patients carrying specific mutations, but some issues especially relating to breast-conserving surgery or administration of radiotherapy in these patients, still need to be better addressed. Opinions about the best way to treat these patients are still heterogeneous and information deriving from different sources seems to be conflicting at times. Our purpose is to offer a synopsis of the different evidence available that may be helpful in clinical decision making.

Surgical and Oncologic Outcomes of Robotic and Conventional Nipple-Sparing Mastectomy with Immediate Reconstruction: International Multicenter Pooled Data Analysis.

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) has been developed to reduce conspicuous scar and increase the quality of life in women. This study aimed to evaluate the surgical and oncologic outcomes of RNSM with immediate breast reconstruction (IBR) compared with conventional nipple-sparing mastectomy (CNSM). PATIENTS AND METHODS: This international multicenter, pooled analysis of individual patient-level data enrolled a total of 755 procedures in 659 women (609 had breast cancer and 50 underwent risk-reducing mastectomy) who underwent nipple-sparing mastectomy with IBR. Surgical and oncologic outcomes, including 30-days postoperative (POD 30d) complication rate, nipple necrosis rate, grade of Clavien-Dindo classification, disease-free survival, and overall survival, were evaluated. Propensity score-matched analyses were performed to adjust for confounding factors. RESULTS: The median age of both the RNSM and CNSM groups was 45 years. The RNSM group had lower body mass index (BMI) and a higher proportion of benign disease compared with the CNSM group. POD 30d complications and postoperative complication grade III rates were lower in the RNSM group than in the CNSM group (p < 0.05). The nipple necrosis rate was 2.2% and 7.8% for RNSM and CNSM, respectively (p = 0.002). After propensity score matching, significantly lower rates of POD 30d complications, nipple necrosis, and postoperative complication grade III occurred in the RNSM group than in the CNSM group (all p < 0.05). Oncologic outcomes were not significantly different between the two groups. CONCLUSION: RNSM can provide better cosmetic results with favorable surgical and oncologic outcomes for women with early breast cancer or BRCA mutation.

A Randomized Trial of Robotic Mastectomy Versus Open Surgery in Women With Breast Cancer or BrCA Mutation.

OBJECTIVE: The aim of this study was to compare robotic mastectomy with open classical technique outcomes in breast cancer patients. SUMMARY BACKGROUND DATA: As the use of robotic nipple sparing mastectomy continues to rise, improved understanding of the surgical, oncologic, and quality of life outcomes is imperative for appropriate patient selection as well as to better understand indications, limits, advantages, and dangers. METHODS: In a phase III, open label, single-center, randomized controlled trial involving 80 women with breast cancer (69) or with BRCA mutation (11), we compared the outcome of robotic and open nipple sparing mastectomy. Primary outcomes were surgical complications and quality of life using specific validated questionnaires. Secondary objective included oncologic outcomes. RESULTS: Robotic procedure was 1 hour and 18 minutes longer than open (P < 0.001). No differences in the number or type of complications (P = 0.11) were observed. Breast-Q scores in satisfaction with breasts, psychosocial, physical and sexual well-being were significantly higher after robotic mastectomy versus open procedure. Respect to baseline, physical and sexual well-being domains remained stable after robotic mastectomy, whereas they significantly decreased after open procedure (P < 0.02). The overall Body Image Scale questionnaire score was 20.7 ±â€Š13.8 versus 9.9 ±â€Š5.1 in the robotic versus open groups respectively, P < 0.0001. At median follow-up 28.6months (range 3.7-43.3), no local events were observed. CONCLUSIONS: Complications were similar among groups upholding the robotic technique to be safe. Quality of life was maintained after robotic mastectomy while significantly decrease after open surgery. Early follow-up confirm no premature local failure.ClinicalTrials.gov NCT03440398.

Advances and controversies in management of breast ductal carcinoma in situ (DCIS).

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. It accounts for 25% of all breast cancers diagnosed, as a result of the expansion of breast cancer screening and is associated with a high survival rate. DCIS is particularly clinically challenging, due to its heterogeneous pathological and biological traits and its management is continually evolving towards more personalized and less aggressive therapies. This article suggests evidence-based guidelines for proper DCIS clinical management, which should be discussed within a multidisciplinary team in order to propose the most suitable approach in clinical practice, taking into account recent scientific studies. Here we include updated multidisciplinary treatment protocols and techniques in accordance with the most recent contributions published on this topic in the peer-reviewed medical literature, and we outline future perspectives.

From cadaveric and animal studies to the clinical reality of robotic mastectomy: a feasibility report of training program.

Robotic nipple-sparing mastectomy (RNSM) provides better cosmetic outcomes and improves the quality of life of women with breast cancer. However, this has not been widely adapted due to the lack of well-structured training programs. The present study aimed to report the establishment of cadaveric and animal skill laboratory training programs for RNSM and the participants' perception on the training programs. We performed 24 RNSMs using 11 cadavers and one porcine model. Then, the skill laboratory characteristics were reviewed. Five trainers and 10 trainees participated in the programs. The first four cadaveric RNSMs with latissimus dorsi flaps and implants were performed using the da Vinci Si® system. We performed 14 and six RNSMs using the Xi® and SP® systems, respectively. The scores for questionnaires on the satisfaction with the training consisted of the trainees' perceived goals in attending the course, teaching/learning environment, and teaching staff performance. The scores were excellent. Cadaveric or porcine RNSM skill laboratory training may be essential programs that can provide safe and efficient training.

Metaplastic breast cancer: Prognostic and therapeutic considerations.

INTRODUCTION: Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting. METHODS: We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic-pathological factors, number and type of events during follow-up were considered to evaluate overall survival (OS) and invasive disease-free survival (IDFS). RESULTS: The majority of MBC was triple-negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki-67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple-negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5-fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting. CONCLUSION: Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease-free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.

Transumbilical Single-port Robotically Assisted Nipple-sparing Mastectomy: A Cadaveric Study.

The authors performed a transumbilical, single-port robotically assisted, nipple-sparing mastectomy on a cadaveric model to assess technical feasibility. Surgeon-controlled, robotic-wristed instrumentation, as well as 3-dimensional high definition (HD) vision allowed the entire dissection to be performed through a single incision placed in the umbilicus. The technique warrants further exploration and development before any application in clinical applied research.

Development of Robotic Mastectomy Using a Single-Port Surgical Robot System.

Minimal invasive surgical technique has been increasingly applied to breast surgery. Since the first robot-assisted nipple-sparing mastectomy was introduced, we have been performing nipple-sparing mastectomy using multi-port robotic surgical system. Last year, the new robotic surgical system with single port was introduced. We report the development of a robotic nipple-sparing mastectomy with immediate reconstruction through a single incision using the updated single-port surgical robot system for a patient with ductal carcinoma in situ (DCIS). Breast reconstruction was performed using implants. Postoperative pathological examination revealed DCIS in both breasts. There were no major immediate complications, except for a minor skin burn on the right breast. Overall, the initial operation using the updated platform was safely performed.

Consensus Statement on Robotic Mastectomy-Expert Panel From International Endoscopic and Robotic Breast Surgery Symposium (IERBS) 2019.

OBJECTIVES: To achieve a consensus statement on robotic mastectomy. BACKGROUND: Robotic-assisted surgery has gained much attention especially the results of few case series reporting on the technical feasibility, safety and early oncologic outcomes of robotic-assisted mastectomy in a few centers worldwide. The aim of this consensus statement was to develop and provide standardized guidelines on robotic mastectomy based on consensus statement by a panel of experts from indications to outcome measures and indicators, thereby providing a valuable guide for breast surgeons worldwide. METHODOLOGY: An internationally representative expert panel of 10 surgeons was invited to participate in the generation of a consensus statement. 52 statements were created in 6 domains: indications, contraindications, technical considerations, patient counseling, outcome measures and indicators, training and learning curve assessment. Experts were asked to vote if they agree, disagree or of the opinion that the statement should be rephrased. Two electronic rounds via online survey of iterative rating and feedback were anonymously completed, followed by a final round of in-person meeting during the inaugural International Endoscopic and Robotic Breast Surgery Symposium 2019 from May 24 to 25, 2019. Consensus was reached when there was at least 80% agreement on each statement. RESULTS: A total of 53 statements with at least 80% agreement were generated after 3 rounds of voting; 21 statements from first round of voting, 20 statements from second round of voting and 12 statements from the final round of in-person meeting. All experts agreed that the consensus statement served as expert recommendations but not mandatory for a successful and safe practice of robotic mastectomy. CONCLUSION: Robotic mastectomy is a promising technique and could well be the future of minimally invasive breast surgery whereas proving to be safe and feasible. The first consensus statement on robotic mastectomy from an international panel of experts serves as an extremely important milestone and provides recommendations for breast surgeons keen to embark on this technique.

Update on the Feasibility and Progress on Robotic Breast Surgery.

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) may allow for more precise anatomic dissection and improved cosmetic outcomes over conventional open nipple-sparing mastectomy; however, data regarding the feasibility and safety of the procedure are limited. OBJECTIVE: The aim of this study was to present and discuss perioperative surgical outcomes and early oncologic follow-up data on consecutive patients undergoing RNSM from June 2014 to January 2019. METHODS: Patients underwent RNSM and immediate robotic breast reconstruction through an axillary incision at a single institution. Perioperative data, complications at 3 months postoperatively, pathological data, and adjuvant therapies were recorded. Local recurrence-free, disease-free, and overall survival were analyzed. RESULTS: Overall, 73 women underwent 94 RNSM procedures. Indications were invasive breast cancer in 39 patients, ductal carcinoma in situ in 17 patients, and BRCA mutation in 17 patients. Mean surgery time was 3 h and 32 min. One-step reconstruction with implant occurred in 89.4% of procedures. The rate of complications requiring reoperation was 4.3%, and the rate of flap or nipple necrosis was 1.1%. Median follow-up was 19 months (range 3.1-44.8). No local recurrences occurred. Overall survival at 12, 24, or 60 months was 98% (95% confidence interval 86-100%). CONCLUSION: We observed a low complication rate in 94 consecutive RNSM procedures, demonstrating the procedure is technically feasible and safe. We found no early local failures at 19 months follow-up. Long-term follow-up is needed to confirm oncologic safety. Future clinical trials to study the advantages and disadvantages of RNSM are warranted.

Oncological Outcomes of Nipple-Sparing Mastectomy: A Single-Center Experience of 1989 Patients.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly used in women with breast cancer who are not eligible for conservative surgery, but extensive outcome data are lacking and indications have not been established. OBJECTIVE: The aim of this study was to assess the oncological outcomes of NSM in a large series of patients with invasive or in situ breast cancer treated at a single center. METHODS: We analyzed 1989 consecutive women who had an NSM in 2003-2011, for invasive (1711 patients) or in situ cancer (278 patients) at the European Institute of Oncology, Italy, and followed-up to December 2016. Endpoints were local recurrences, recurrences in the nipple-areola complex (NAC), NAC necrosis, and overall survival (OS). RESULTS: After a median follow-up of 94 months (interquartile range 70-117), 91/1711 (5.3%) patients with invasive cancer had local recurrence (4.8% invasive disease, 0.5% in situ disease), and 11/278 (4.0%) patients with in situ disease had local recurrence (1.8% invasive disease, 2.2% in situ disease). Thirty-six (1.8%) patients had NAC recurrence, 9 with in situ disease (4 invasive and 5 in situ recurrences), and 27 with invasive disease (18 invasive and 9 in situ recurrences). NAC loss for necrosis occurred in 66 (3.3%) patients. There were 131 (6.6%) deaths, 109 (5.5%) as a result of breast cancer. OS at 5 years was 96.1% in women with invasive cancer and 99.2% in women with in situ disease. CONCLUSIONS: The findings in this large series, with a median follow-up of nearly 8 years, indicate that NSM is oncologically safe for selected patients. The rate of NAC loss was acceptably low.