Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1-2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial.

BACKGROUND: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. METHODS: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). RESULTS: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). CONCLUSIONS: The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND.

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.

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.

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.

Ipsilateral Breast Cancer Recurrence: Characteristics, Treatment, and Long-Term Oncologic Results at a High-Volume Center.

INTRODUCTION: Salvage mastectomy is considered the treatment of choice for ipsilateral breast cancer recurrence (IBCR), even if a second breast-conserving surgery (BCS) is feasible. The purpose of this study was to describe the characteristics of IBCR patients, to compare the 2 therapeutic options in terms of long-term outcomes, and to identify independent factors that may predict the type of treatment. PATIENTS AND METHODS: A total of 309 IBCR patients who underwent either repeat BCS or mastectomy were identified. All the analyzed patients with IBCR had true recurrence. RESULTS: Repeat BCS and salvage mastectomy were performed in 143 and 166 patients, respectively. Age < 65 years (59.6% vs 37.1% if age ≥ 65 years; odds ratio, 2.374; 95% confidence interval, 0.92-5.24; P = .018) and disease-free interval < 24 months (15.7% vs 10.5% if disease-free interval ≥ 24 months; odds ratio, 2.705; 95% confidence interval, 1.42-5.97; P = .007) were found to significantly increase the probability of receipt of mastectomy. Disease-free survival rates at 3, 5, and 10 years were 79.2%, 68.2%, and 36.9%; and 77.2%, 65.9%, and 55.3% in patients receiving repeat BCS or mastectomy, respectively (P = .842). Overall survival rates at 3, 5, and 10 years were 95.4%, 91.4%, and 68.5%; and 87.3%, 69.3%, and 57.9%, respectively, in patients receiving repeat BCS or mastectomy (P = .018). CONCLUSION: Salvage mastectomy should not be considered the only treatment option for IBCR. A second BCS can still be evaluated and proposed to IBCR patients, with acceptable locoregional control and survival. The risk of poor long-term prognosis after mastectomy should be shared with the patient.

Internal mammary lymph node siliconoma in absence of prosthesis rupture: a case series that raises concern for potential risk of overdiagnosis.

BACKGROUND: Silicon migration after rupture is an adverse event of breast implant, whose risk increases with the aging of prosthesis. The exact prevalence of this complication remains unclear and reported data are inconsistent. In addition, microscopic diffusion of silicone gel through intact implant, known as gel bleeding, might verify thus complicating diagnosis. Although high cohesive gel has reduced the occurrence of gel bleeding, this phenomenon is still possible and its occurrence rate remains underestimated. If silicon droplets migrate in locoregional lymph node, a swelling that mimics recurrence can arise. Therefore, a risk of overdiagnosis is possible when clinicians rely only on imaging techniques. The aim of this study is to evaluate the actual prevalence of metastasis in internal mammary lymph node (IMLN) in presence of PET positive uptake and no prosthesis rupture. METHODS: We retrospectively evaluated our patient's records and selected those with intact breast implants and suspected relapse in IMLN that underwent biopsy, either surgical or imaging guided. All patients performed PET/CT scan showing pathological uptake in IMLNs. A breast magnetic resonance (MRI) or ultrasound (US) imaging confirmed a suspicious adenopathy and excluded prosthesis rupture. From 2015 to 2019 a total of nine patients underwent biopsy of the IMLN and only six of them met inclusion criteria. RESULTS: Four biopsies were CT-guided, two were surgical. Three patients (50%) were diagnosed with breast cancer relapse while two (33.3%) were found with siliconoma and one (16.7%) was inflammatory. CONCLUSIONS: Siliconoma can occur even without evidence of capsule rupture, challenging the clinicians and leading to a risk of relapse over diagnosis. Echographic, MRI and nuclear medicine imaging criteria may be not sufficient in differential diagnosis. To overcome the issue, we suggest introducing into the clinical practice the biopsy of suspicious enlarged IMLN with minimally invasive technique.

Correlation between outcome and extent of residual disease in the sentinel node after neoadjuvant chemotherapy in clinically fine-needle proven node-positive breast cancer patients.

BACKGROUND: Whether the extent of residual disease in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC) influences the prognosis in clinically node-positive breast cancer (BC) patients remains to be ascertained. METHODS: One hundred and thirty-four consecutive cN+/BC-patients received NAC followed by SLN biopsy and axillary lymph node dissection. Cumulative incidence of overall (OS) and disease-free (DFS) survival, BC-related recurrences and death from BC were assessed using the Kaplan-Meier method both in the whole patient population and according to the SLN status. The log rank test was used for comparisons between groups. RESULTS: The SLN was identified in 123/134 (91.8%) patients and was positive in 98/123 (79.7%) patients. Sixty-five of them (66.3%) had other axillary nodes involved. SLN sensitivity and false-negative rate were 88.0% and 2.0%, Median follow-up was 10.2 years. Ten-year cumulative incidence of axillary, breast and distant recurrences, and death from BC were 6.5%, 11.9%, 33.4% and 31.3%, respectively. Ten-year OS and DFS were 67.3% and 55.9%. When stratified by SLN status, 10-year cumulative incidence of BC-related and loco-regional events, and death from BC were similar between disease-free SLN and micrometastatic SLN subgroups (28.9% vs 30.2%, p = 0.954; 21.6% vs 13.4%, p = 0.840; 12.9 vs 24.5%, p=0.494). Likewise, 10-year OS and DFS were comparable (80.0% vs 75.5%, p=0.975 and 68.0% vs 69.8, p=0.836). Both OS and DFS were lower in patients presenting a macrometastatic SLN (60.2% and 47.5%). CONCLUSION: Outcome of patients with micrometastatic SLN was similar to that of patients with disease-free SLN, which was more favorable as compared to that of patients with macrometastatic SLN.

Neoadjuvant chemotherapy in hormone receptor-positive/HER2-negative early breast cancer: When, why and what?

Indication for neoadjuvant chemotherapy (NACT) in HR+/HER2-negative tumors is controversial. Pathological complete response (pCR) rates range from 0 to 18 % while breast-conserving surgery (BCS) is achievable in up to 60 % of tumors. No pathological feature definitely predicts pCR; lobular and molecular luminal A tumors are less likely to achieve pCR although experiencing better outcomes. Luminal B subtype, high proliferation, lack of progesterone receptor, high tumor-infiltrating lymphocytes are positively associated with increased pCR rates but worse outcomes and the prognostic role of pCR is inconsistent across studies. Molecular intrinsic subtyping and genomic signatures appear as more accurate predictors of benefit from NACT, but larger studies are needed. Anthracycline and taxane-based chemotherapy remains the standard NACT; however, CDK 4/6 inhibitors and immune checkpoint inhibitors are under evaluation. In conclusion, NACT may be proposed for luminal tumors requiring downsizing for BCS after multidisciplinary evaluation, provided that other contraindications to BCS are excluded.

PONDx: real-life utilization and decision impact of the 21-gene assay on clinical practice in Italy.

Clinicopathological prognostic features have limited value to identify with precision newly diagnosed patients with hormone receptor (HR)-positive, HER2-negative breast cancer (BC), who would benefit from chemotherapy (CT) in addition to adjuvant hormonal therapy (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay has been demonstrated to predict CT benefit, hence supporting personalized decisions on adjuvant CT. The multicenter, prospective, observational study PONDx investigated the real-life use of RS® results in Italy and its impact on treatment decisions. Physicians' treatment recommendations (HT ± CT) were documented before and after availability of RS results, and changes in recommendations were determined. In the HR+ HER2- early BC population studied (N = 1738), physicians recommended CT + HT in 49% of patients pre-RS. RS-guided treatment decisions resulted in 36% reduction of CT recommendations. PONDx confirms that RS results provide clinically relevant information for CT recommendation in early-stage BC, resulting in a reduction of more than a third of CT use.

Evolution and time trends of nipple-sparing mastectomy: a single-center experience.

Nipple Sparing Mastectomy (NSM) requires the entire breast tissue to be removed, maintaining the nipple-areola complex, and represents nowadays the gold standard of the demolitive breast surgery. Although it represents the evolution of conservative breast surgery, NSM presents some limitations in the selection of women candidates for treatment, and still there are no real guidelines regarding its indications, but simply objective data to address the choice. How the breast surgery approach to demolitive and conservative surgery has changed over time? We evaluated throughout the years (from 2009 up to 2018) the time trend of NSM at our institution and analysed the main differences between patients undergone NSM and other mastectomies and/or breast conserving surgery in terms of cancer size, multicentricity and biological profile. We found 781 NSMs, 1261 other mastectomies and 5621 breast conservative surgeries. Among NSMs, 39.6% were reconstructed with tissue expander and 58.1% with definitive prosthesis. From 2009 to 2018 we found a general increase of NSM rate (from 21.3% of all mastectomies in 2009 to 67.3% in 2018) and a decrease of total mastectomies (from 78.7% of all mastectomies in 2009 to 32.7% in 2018). In line with the literature data, our data confirm that in the recent years NSM represents the gold standard for radical breast surgery. Undisputed in prophylaxis, NSM is continuously acquiring more support in being used as first line treatment for locally advanced disease.

Mucinous breast cancer: A narrative review of the literature and a retrospective tertiary single-centre analysis.

Mucinous carcinoma (MC) is a rare breast cancer characterized by the presence of large extracellular mucin amount. Two main subtypes can be distinguished: pure (PMC) and mixed (MMC). We conducted a retrospective MC analysis in our prospective maintained database, calculating disease-free survival (DFS) and 5-year overall survival (OS). We found a global 92.1% OS (higher in MMC group and statistically significative) and a DFS of 95.3% (higher in MMC group but not statistically significative).

[Thyroid carcinoma: from diagnosis to therapy]. / Il carcinoma della tiroide dalla diagnosi alla terapia.

From 1999 to 2007 we performed 104 surgical operations for thyroid malignancies. Over the same period, 312 patients underwent surgery for benign lesions of the thyroid gland. The patients were subdivided on the basis of age bracket and gender and the distribution of cancer and benign nodules was evaluated. Feasibility and diagnostic accuracy of ultrasonography, scintigraphy and fine needle aspiration cytology were also evaluated. The incidence of thyroid cancer was 25% in all patients. Patients aged < 30 years and > 71 had the highest rate of malignancies: 52% of patients under 30 years of age and 46% over 70 years. Males showed a higher incidence than females. The scintigraphic findings were an area of low uptake in 19 cases (47.5%), an irregular pattern in 12 patients (30%) and a high uptake in 9 cases (22.5%); in 3 of them (7.5%), cancer was in the contralateral lobe and in 2 cases (5%) the dimensions were 8 and 4 mm. Forty-three patients had a single hypoechoic nodule at ultrasonography (41.3%), 3 (3%) were found with hypoechoic nodules containing calcifications and 1 (0.9%) a single anechoic nodule. Fifty-six patients (53.9%) had multiple nodules and 1 (0.9%) was admitted for a latero-cervical lymph node. FNAC revealed 11 cases of fibronectin expression (14.4%): in particular, 3 patients (4%) had cancer in the contralateral lobe and 3 patients (4%) had tumours measuring less than 5 mm. Thyroid surgery is safe and the morbidity rate is about 2%. We observed only one lesion of recurrent nerve (0.5% of patients), temporary recurrent palsy in 2.8% of patients and transient hypocalcaemia in 6.7% of cases.

Does Conservative Surgery for Breast Carcinoma Still Require Axillary Lymph Node Evaluation? A Retrospective Analysis of 1156 Consecutive Women With Early Breast Cancer.

BACKGROUND: The role of axillary surgery for early breast carcinoma treated with conservative surgery and radiotherapy is currently the subject of considerable investigation. Recent studies have supported the noninferiority of avoiding axillary surgery in terms of overall survival when sentinel lymph node biopsy (SLNB) presents ≤ 2 positive lymph nodes, thus sparing the patients from complications. There are some ongoing studies investigating the possibility of omitting SLNB. Axillary study seems to be sufficiently replaced by SLNB for staging the disease. Axillary surgery maintains a therapeutic role in the presence of > 2 metastatic lymph nodes at SLNB. PATIENTS AND METHODS: We performed a retrospective analysis of 1156 patients with early breast cancer to estimate the real incidence of patients with T1 tumors presenting > 2 metastatic lymph nodes. RESULTS: Of the 1156 cases, only 106 (9.2%) had > 2 axillary metastatic lymph nodes. More specifically, 38 (4.3%) of 884 T1 cases, and 6 (2.3%) of 257 of T1b cases had > 2 metastatic lymph nodes. CONCLUSION: The advantage of axillary surgery seems to be limited only to a specific subgroup of T1 patients who are undergoing conservative surgery plus radiotherapy. The ongoing studies on avoiding SLNB will likely prove the noninferiority of omitting biopsy because these studies are conducted in the whole population of early breast cancers. It is necessary to identify more accurately the subpopulation of patients who may benefit from axillary surgery.

Breast cancer subtypes can be determinant in the decision making process to avoid surgical axillary staging: A retrospective cohort study.

INTRODUCTION: The need for performing axillary lymph-node dissection in early breast cancer when the sentinel lymph node (SLN) is positive has been questioned in recent years. The purpose of this study was to identify a low-risk subgroup of early breast cancer patients in whom surgical axillary staging could be avoided, and to assess the probability of having a positive lymph-node (LN). METHODS: We evaluated the cohort of 612 consecutive women affected by early breast cancer. We considered age, tumor size, histological grade, vascular invasion, lymphatic invasion and cancer subtype (Luminal A, Luminal B HER-2+, Luminal B HER-2-, HER-2+, and Triple Negative) as variables for univariate and multivariate analyses to assess probability of there being a positive SLN o nonsentinel lymph node (NSLN). Chi-square, Fisher's Exact test and Student's t tests were used to investigate the relationship between variables; whereas logit models were used to estimate and quantify the strength of the relationship among some covariates and SLN or the number of metastases. RESULTS: A significant positive effect of vascular invasion and lymphatic invasion (odds ratios are 4 and 6), and a negative effect of TN (odds ratios is 10) were noted. With respect to positive NSLN, size alone has a significant (positive) effect on tumor presence, but focusing on the number of metastases, also age has a (negative) significant effect. CONCLUSION: This work shows correlation between subtypes and the probability of having positive SLN. Patients not expressing vascular invasion, lymphatic invasion and, moreover, a triple-negative tumor subtype may be good candidates for breast conservative surgery without axillary surgical staging.

Localization of sentinel lymph node in breast cancer. A prospective study.

INTRODUCTION: Sentinel Lymph Node Biopsy (SLNB) is the standard of care for staging axillary lymph nodes in women with breast cancer and clinically negative nodes. It is associated with reduced arm morbidity, moderated or severe lymphoedema, and a better quality of life in comparison with standard axillary treatment. Unfortunately, skip metastases makes all minimally invasive approaches, such as axillary sampling, unreliable. The aim of the present clinical prospective study is to evaluate the position of SLN in an important number of cases and establish the real incidence of skip metastases in clinically node-negative patients. PATIENTS AND METHODS: A cohort of 898 female patients with breast carcinoma was considered, from 2001 to 2008. Once SLN was localized, by means of radio-colloid or blue dye staining, and isolated, a biopsy was performed. Only those positive for metastases were submitted to axillary dissection. RESULTS: Only in nine cases a SLN was not isolated. We had 819 cases of first level SLN (group A) and 69 cases of second level SLN (group B). Considering all of 889 cases, SLN was localized in the second level in 69 patients (7.8%); but if we consider metastatic SLN alone (340 cases), it was in the second level in 23 subjects (6.8%). In total, we had a positive second level SLN in 2.3% of cases (23/889). CONCLUSION: Second level SLN could be considered only an anomalous lymphatic axillary drainage and it does not linked to particular histological variants of the primitive tumour. In our study, skip metastases were recognized in only 2.6% of cases, therefore, whenever a SLN is not isolated for any reason, the first level sampling represent a viable operative choice.

Sarcoma of the breast: outcome and reconstructive options.

INTRODUCTION: Surgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances. MATERIALS AND METHODS: Data from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated. RESULTS: Thirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06). CONCLUSION: Secondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.