Intraoperative ultrasound margin evaluation as a tool to reduce positive superficial margins in nipple and skin sparing mastectomy in breast cancer patients.

BACKGROUND: Intraoperative ultrasound (IOUS) guided conservative surgery has been shown to reduce rates of positive margins in breast cancer. The aim of the study is to evaluate the feasibility of using IOUS to assess superficial/anterior margins in nipple and skin sparing mastectomy (NSM/SSM) and its impact on reducing rates of positive margins. METHODS: This prospective study includes all breast cancer patients who had an indication for NSM/SSM at our Institution. Superficial margin width was measured by IOUS before surgery and the area marked on the skin. Same measurement was performed afterwards in the mastectomy specimen. Any superficial margin < 5 mm was re-excised intraoperatively following the mark on the skin. RESULTS: Fifty-nine patients were included, 47 patients (79.7%) underwent NSM, and 12 patients (20.3%) a SSM. Of the 59 patients, 23 (38.98%) had margins ≥5 mm and 36 patients (61.02%) had margins of ≤5 mm. Of the 36 patients with superficial margins ≤5 mm, 20 had margins <2 mm, and 6 of them had intraoperative involved superficial margins in final pathology. However, after IOUS-guided re-excision, final pathology showed no involved margins. A 2 mm margin was set as the cut-off point for performing an intraoperative re-excision. IOUS guided re-excisions for intraoperative margins ≤2 mm significantly reduced the risk of close/positive margins in final pathology, p < 0.0001. CONCLUSION: The results showed that IOUS margin evaluation significantly reduced the rate of superficial positive margins in NSM/SSM. It is feasible and effective and may avoid challenging reoperations and/or additional radiation therapy for positive margins.

Feasibility and safety of targeted axillary dissection guided by intraoperative ultrasound after neoadjuvant treatment.

BACKGROUND: Axillary management in cN + axillary nodes after neoadjuvant systemic therapy (NST) in breast cancer (BC) remains under research with the aim of de-escalation of axillary node dissection (ALND). Several axillary guided localization techniques have been reported. This study evaluates the safety of intraoperative ultrasound (IOUS) guided targeted axillary dissection (TAD) in a large sample after the results of ILINA trial. MATERIALS: Prospective data have been collected from October 2015 to June 2022 in patients with cT0-T4 and positive axillary lymph nodes (cN1) treated with NST. Before NST, an ultrasound visible marker was placed into the positive node. After NST, IOUS guided TAD was performed including sentinel node biopsy (SLN). Until December 2019, all patients underwent an ALND after TAD procedure. From January 2020, ALND was spared in those patients with an axillary pathological complete response (pCR). RESULTS: 235 patients were included. pCR (ypT0/is ypN0) was achieved in 29% patients. Identification rate (IR) of the clipped node by IOUS was 96% (95% IC, 92.5-98.1%) and IR of SLN was 95% (95% IC, 90.8-97.2%). False negative rate (FNR) for TAD procedure (SLN + clipped node) was 7.0% (95% IC, 2.3-15.7%), which decreased to 4.9% when a total of 3 or more nodes were removed. Axillary ultrasound before surgery assessed residual disease with an AUC of 0.5241. Residual axillary disease tend to be the most significant factor for axillary recurrences. CONCLUSIONS: This study confirms the feasibility, safety and accuracy of IOUS guided surgery for axillary staging after NST in node positive BC patients.

Intraoperative Ultrasound-Guided Excision of Non-Palpable and Palpable Breast Cancer: Systematic Review and Meta-Analysis.

Wire-guided localization (WGL) is the most frequently used localization technique in non-palpable breast cancer (BC). However, low negative margin rates, patient discomfort, and the possibility of wire dislocation have been discussed as potential disadvantages, and re-operation due to positive margins may increase relapse risk. Intraoperative ultrasound (IOUS)-guided excision allows direct visualization of the lesion and the resection volume and reduces positive margins in palpable and non-palpable tumors. We performed a systematic review on IOUS in breast cancer and 2 meta-analyses of randomized clinical trials (RCTs). In non-palpable BC, 3 RCTs have shown higher negative margin rates in the IOUS arm compared to WGL. Meta-analysis confirmed a significant difference between IOUS and WGL in terms of positive margins favoring IOUS (risk ratio 4.34, p < 0.0001, I2 = 0%). 41 cohort studies including 3291 patients were identified, of which most reported higher negative margin and lower re-operation rates if IOUS was used. In palpable BC, IOUS was compared to palpation-guided excision in 3 RCTs. Meta-analysis showed significantly higher rates of positive margins in the palpation arm (risk ratio 2.84, p = 0.0047, I2 = 0%). In 13 cohort studies including 942 patients with palpable BC, negative margin rates were higher if IOUS was used, and tissue volumes were higher in palpation-guided cohorts in most studies. IOUS is a safe noninvasive technique for the localization of sonographically visible tumors that significantly improves margin rates in palpable and non-palpable BC. Surgeons should be encouraged to acquire ultrasound skills and participate in breast ultrasound training.

Four-fraction ultra-accelerated minimal breast irradiation in early breast cancer: The initial feasibility results of an institutional experience.

PURPOSE: To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). METHODS AND MATERIALS: Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ≤3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. RESULTS: Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9-75.4 cc), and the external-V100 was 43.1 cc (12.87-107 cc), representing 5% of the breast tissue irradiated with a median CTV D90 of 6.2 Gy (5.6-6.28 Gy). The entire local treatment (BCS&MITBI-4f-AMBI) was completed at a median of 8 days (4-10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11-51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. CONCLUSIONS: Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes.

Health-Related Quality of Life After Nipple-Sparing Mastectomy: Results From the INSPIRE Registry.

INTRODUCTION: Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is increasingly used for both breast cancer (TNSM) and risk reduction (RRNSM). The aim of the study is to report the results of the INSPIRE registry assessing health-related quality of life (HRQoL) comparing baseline and 1-year follow-up, regarding surgical indications and chemotherapy (CT) received. METHODS: INSPIRE is a prospective database including women undergoing NSM and IBR from 18 countries. HRQoL was measured using EORTC QLQC30 and QLQ-BR23 before surgery and after 1 year. RESULTS: A total of 677 women were included, of whom 537 (79.3%) underwent TNSM and 140 (21.6%) RRNSM: in total, 806 NSM (556 TNSM and 250 RRNSM). Nipple involvement was present in 7.73% of TNSM and incidental carcinoma in 1.2% of the RRNSM group. Out of the overall 537 patients with systemic treatment, 177 (32.96%) received neoadjuvant chemotherapy (NCT) and 118 (21.92%) adjuvant chemotherapy (CT). A total of 227 patients (28.16%) developed at least one complication postoperatively, 164 (29.5%) in the TNSM group and 63 (25.2%) in the RRNSM group. The TNSM group improved in global health status and emotional functioning after 1 year. No differences were found when comparing HRQoL at 1 year between patients who received NCT and those who received adjuvant CT. The RRNSM group showed improvement in HRQoL, with better emotional functioning and fatigue after 1 year. CONCLUSIONS: This registry reports HRQoL findings after NSM. The impact of CT on worse HRQoL is independent from its timing. Patients with RRNSM showed an improved HRQoL at 1-year follow-up. Discussion of HRQoL outcomes with patients will facilitate the informed decision-making when considering NSM.

Leveraging the increased rates of pathologic complete response after neoadjuvant treatment in breast cancer to de-escalate surgical treatments.

INTRODUCTION: Breast conservative surgery (BCS) and sentinel lymph node biopsy (SLNB) after neoadjuvant treatment (NAT) is safe and effective for selected patients. This aim of this study is to evaluate the impact of anatomic site of response on outcomes and to assess the real population who may benefit from nonsurgical approaches after NAT. MATERIAL AND METHODS: From a prospectively maintained database, patients with T1-4 N0-2 breast cancer undergoing NAT were identified. Clinicopathological and survival rates were compared in relation to response and anatomic site of response. RESULTS: Six hundred and forty-six patients were included in the study. Pathologic complete response (pCR) was an independent factor for BCS and SLN. HER2 positive and TN tumors with cN0 achieving a breast pCR remain ypN0 (p = .002). Residual axillary disease was associated with breast residual tumor (p = .05) and subtype (p = .001). With a median follow up of 35.25 months, patients with any pCR had improved survival when compared with partial response, but not significant differences between pCR, axillary pCR, or breast pCR. CONCLUSION: Achieving a pCR increases BCS and SLN. In selected subgroups, sparing any axillary surgery after NAT maybe feasible. In cN+ patients, any pCR was associated with survival, but not the anatomic site of response.

A randomized study comparing different doses of superparamagnetic iron oxide tracer for sentinel lymph node biopsy in breast cancer: The SUNRISE study.

INTRODUCTION: The non-radioactive method that uses the magnetic tracer (SPIO/Sienna) has shown to be a feasible technique for the SLN detection in breast cancer patients. The aim of this study is to assess the efficacy of different doses of a new magnetic tracer Sienna XP (Magtrace) compared to Tc-99 m and to evaluate its non-inferiority. METHODS: Patients diagnosed with early-stage breast cancer cT1-3 N0, from October 2016 to August 2018 were eligible and consecutively randomized to three different doses of new SPIO used: group 1 (1 mL), group 2 (1.5 mL) and group 3 (2 mL). RESULTS: A total of 135 patients were included in the study, 45 in each group. Detection of SLNs with the three doses of Sienna XP (1 mL, 1.5 mL and 2 mL) showed non-inferior rates compared to the conventional technique with radiotracer (p = 0.654). Concordance by patients with SLN positive was 100% for all groups. 83 (70.3%) patients reported skin staining at one month postoperatively, significantly lower in group 1 (p = 0.042). At 6 months follow up, group 1 remains with significantly lower skin discoloration (p = 0,01). In multivariate analysis, dose of 2 mL showed statistically significant for the skin staining. The majority of patients (70%) felt that skin discoloration does not represent a problem. CONCLUSION: The use of the Sienna XP magnetic tracer at 1 mL is not inferior to higher doses of magnetic tracer neither is inferior to radiotracer. 1 mL of magnetic tracer resulted in significantly less skin discoloration compared to higher doses.

Minimally invasive tumor bed implant (MITBI) and peri-operative high-dose-rate brachytherapy (PHDRBT) for accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost) in breast-conserving surgery for ductal carcinoma in situ.

PURPOSE: To evaluate our institutional experience of minimally invasive tumor bed implantation (MITBI) during breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) to deliver peri-operative high-dose-rate brachytherapy (PHDRBT) as accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost). MATERIAL AND METHODS: Patients older than 40, with clinical and radiological unifocal DCIS < 3 cm were considered potential candidates for accelerated partial breast irradiation (APBI) and were implanted during BCS using MITBI-technique. Patients who in final pathology reports showed free margins and no other microscopic tumor foci, received AMBI with PHDRBT (3.4 Gy BID in 5 days). Patients with adverse features received A-PHDRBT-boost with post-operative external beam radiotherapy (EBRT). RESULTS: Forty-one patients were implanted, and 36 were treated and analyzed. According to final pathology, 24 (67%) patients were suitable for AMBI and 12 (33%) were qualified for A-PHDRBT-boost. Reoperation rate for those with clear margins was 16.6% (6/36); this rate increased to 33% (4/12) for G3 histology, and 66% (4/6) were rescued using AMBI. Early complications were documented in 5 patients (14%). With a median follow-up of 97 (range, 42-138) months, 5-year rates of local, elsewhere, locoregional, and distant control were all 97.2%. 5-year ipsilateral breast tumor recurrence rates (IBTR) were 5.6% (2/36), 8.3% (2/24) for AMBI, and 0% (0/12) for A-PHDRBT-boost patients. Both instances of IBTR were confirmed G3 tumors in pre-operative biopsies; no IBTR was documented in G1-2 tumors. Cosmetic outcomes were excellent/good in 96% of AMBI vs. 67% in A-PHDRBT-boost (p = 0.034). CONCLUSIONS: The MITBI-PHDRBT program allows selection of patients with excellent prognoses (G1-2 DCIS with negative margins and no multifocality), for whom AMBI could be a good alternative with low recurrence rate, decrease of unnecessary radiation, treatment logistics improvement, and over-treatment reduction. Patients whose pre-operative biopsy showed G3 tumor, presents with inferior local control and more risk of reoperation due to positive margins.

Learning curves in intraoperative ultrasound guided surgery in breast cancer based on complete breast cancer excision and no need for second surgeries.

BACKGROUND: Intraoperative ultrasound guided surgery (IOUS) is an effective surgical technique for breast cancer with advantages over wire localization guided surgery (WL), enabling smaller lumpectomies without compromising margins. Nevertheless, it has had a slow implementation, maybe due to lacking a learning curve. Also differences in costs are not clearly reported. The aim of the study is to assess differences in volume of healthy breast tissue excised, to establish a learning curve and to prove it is cost saving. PATIENTS AND METHODS: From February 2009 to April 2013, women diagnosed with invasive breast cancer eligible for IOUS or WL breast conserving surgery were recorded into a prospectively maintained database. Both groups were compared for differences in margin status, second surgeries and excess of healthy tissue resected, defined by the calculated resection ratio (CRR). A raw cost study was assessed. IOUS learning curve was analyzed using Cumulative sum control chart (CUSUM). RESULTS: The study included 214 patients, 148 (69.16%) in the IOUS group and 66 (30.84%) in the WL group. IOUS showed significantly smaller surgical volumes (p = 0.02), smaller CRR (p = 0.006), higher rate of negative margins (p = 0.017) and less surgical time (p = 0.006) than WL. Learning curves based on complete tumor excision and no need for second surgeries showed that 11 cases were enough to master the technique. Around 900€ per surgery was saved using IOUS vs. WL. CONCLUSION: IOUS decreases excision of healthy breast tissue while increasing negative margin rates compared to WL. IOUS can be easily implemented; 11 cases are enough to acquire skills for performing the technique. Savings can be up to 900€ per surgery.

Percutaneous ultrasound-guided vacuum-assisted excision of benign breast lesions: A learning curve to assess outcomes.

OBJECTIVE:: To evaluate the efficacy and learning curve of ultrasoundguided vacuum-assisted excision (US-VAE) of benign breast lesions, and to assess characteristics associated with residual lesion. METHODS:: This was a retrospective study with institutional review board-approval. Sonographic and clinical follow-up were performed 6 months after intervention. Effectiveness and safety of the technique were analyzed. The cumulative summation (CUSUM) graphs were used to evaluate learning curves concerning complete excision and hematoma. RESULTS:: 152 ultrasound-VAEs in 143 patients were included. Initial complete resection was achieved in 90.8 % (138 of 152). 6-month follow-up was completed for 143 (94%) of cases and complete resection was observed in 72 % (100 of 143). Mean maximum size without residual tumor was 16.9 mm, while with residual lesion it was 21.9 mm (p = < 0.001), with a volume of 1.53 and 3.39 cm3, respectively (p = < 0.001). Increase in lesion size and volume was associated with less effectiveness (p = 0.05), clinical control (p = 0.05), and higher risk of clinically significant hematoma (p = 0.05). Receiver operating characteristic analysis demonstrate a volume threshold of 2.6 cm3 (r = 0.71, specificity 84.5%) for leaving no residual lesion. Cumulative summation graphs demonstrate that, on average, 11 excisions were required to acquire skills to perform complete excision in more than 80% at the end of the ultrasound-VAE and 18 excisions at 6 months. CONCLUSION:: Ultrasound-VAE is an effective treatment for benign breast lesions. Breast lesion volume should be considered when assessing for percutaneous treatment. ADVANCES IN KNOWLEDGE:: A follow-up of the learning process of ultrasound-VAE will be a valuable tool to assess the efectiveness and safety of the technique i.

Modeling anti-IL-6 therapy using breast cancer patient-derived xenografts.

The pleiotropic cytokine IL-6 accelerates the progression of breast cancer in a variety of preclinical models through the activation of the STAT3 (signal transducer and activator of transcription 3) signaling pathway. However, the proportion of breast cancers sensitive to anti-IL-6 therapies is not known. This study evaluates the efficacy of anti-IL-6 therapies using breast cancer patient derived xenografts (PDXs). During the generation of our collection of PDXs, we showed that the successful engraftment of tumor tissue in immunodeficient mice correlates with bad prognosis. Four PDXs out of six were resistant to anti-IL-6 therapies and the expression of IL-6, its receptor or the levels of phospho-STAT3 (the active form of the signal transducer) did not correlate with sensitivity. Using cell cultures established from the PDXs as well as samples from in vivo treatments, we showed that only tumors in which the activation of STAT3 depends on IL-6 respond to the blocking antibodies. Our results indicate that only a fraction of breast tumors are responsive to anti-IL-6 therapies. In order to identify responsive tumors, a functional assay to determine the dependence of STAT3 activation on IL-6 should be performed.

Detection of sentinel lymph node in breast cancer recurrence may change adjuvant treatment decision in patients with breast cancer recurrence and previous axillary surgery.

Use of sentinel lymph node dissection in patients with ipsilateral breast cancer recurrence is still controversial. The objective of this study is to evaluate the feasibility of the sentinel lymph node in breast cancer recurrence (SLNBR) and whether the positivity had impact in the adjuvant treatment. Between 2008 and 2012 we performed SLNBR in patients with ipsilateral breast tumor recurrence. We included 53 patients in a prospective study. Forty-three patients (81%) had a previous axillary lymph node dissection (ALND) and ten (19%) had a previous sentinel lymph node biopsy (SLNB). Identification rate after SLNB was 50% and after ALND was 60.5% (p = 0.4). Nine patients (26%) had a positive SLNBR. Adjuvant systemic treatment was given to all the patients with a positive SLNBR and to 23 (85%) with a negative SLNBR (p = 0.29). Six patients (66%) with positive SLNBR and 4 patients (14%) with negative SLNBR underwent radiation therapy (p < 0.01). As conclusions of our study we conclude that sentinel lymph node biopsy in breast tumor recurrence is feasible and significant differences were found in the use of radiation therapy in patients with a positive SLNBR.

Surgery improves breast cancer-specific survival in octogenarians with early-stage breast cancer.

INTRODUCTION: No consensus exists on optimum therapy for older cancer patients. This singlecentre study was conducted to review the treatment and outcomes for octogenarian women treated for breast cancer. METHODS: Data of all elderly breast cancer patients (≥80 years) with primary breast cancer treated at out institution between 1990 and 2009. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. Breast cancer-specific survival and disease-free survival for the different patient groups were analysed according to the Kaplan-Meier method. RESULTS: The study population consisted of 259 patients (median age 84 years). There were 189 (73%) patients with early stage disease (I, IIA, IIB) and 70 (27%) with locally advanced disease (IIIA, IIIB, IIIC). A total of 175 (67.7%) patients underwent surgical treatment and 84 (32.4%) received primary endocrine treatment. Patients were followed for a median of 65 months. In patients with early stages, the mean breast cancer-specific survival was 108 months (95% CI 101-115) in the surgical group and 50 months (95% CI 39-61) in the non-surgical group (P < 0.01), whereas patients with locally advanced breast cancer breast cancer-specific survival was similar for the surgical and non-surgical groups. Breast cancer-specific survival and disease-free survival were significantly better among patients who underwent standard surgical treatment than among those with suboptimal surgery. CONCLUSION: In women ≥80 years with early-stage breast cancer, standard surgical treatment as compared with non-surgical therapy was associated with a better breast cancer-specific.

Extensive nodal involvement increases the positivity of blue nodes in the axillary reverse mapping procedure in patients with breast cancer.

BACKGROUND: The axillary reverse mapping (ARM) technique has been proposed to prevent arm lymphedema. We conducted this study to assess the feasibility of the technique and the outcomes of patients with neoadjuvant chemotherapy (NAC). METHODS: From July 2009 to May 2010, a prospective study was performed in 36 patients with breast cancer undergoing an ALND. The ARM technique was performed injecting 3 cm(3) of Patent Blue in the ipsilateral arm. Of the 36 patients, 29 patients received NAC previously to the ARM and 7 patients had an ALND and ARM performed as first treatment for positive axillary nodes. RESULTS: The identification rate of blue nodes was 83.3% (30 patients). Sentinel lymph node (SLN) was performed in 15 of 29 (42%) patients in the NAC group. Of these 15, two patients (13%) had a concordance between the blue and the hot node. Blue nodes were positive in 4 (13%) of the 30 patients. CONCLUSIONS: The ARM technique is feasible in patients undergoing NAC. Patients with extensive nodal involvement have increased risk of having positive blue nodes. More studies are needed to assess the subgroup of patients with positive axilla that may have the blue node spared without compromising the oncological treatment.

Electrothermal bipolar vessel sealing system in axillary dissection: a prospective randomized clinical study.

We assessed whether axillary dissection using the electrothermal bipolar vessel sealing system (LigaSure) improved perioperative outcome when compared with conventional axillary dissection, in a prospective randomized study of 100 women with breast cancer. Those needing axillary dissection were randomized to the use of LigaSure or to conventional axillary dissection (with 50 patients in each group, all of whom had a closed suction drain in the axilla). The LigaSure patients had less intraoperative blood loss (exceeding 199 mL in 30.8% vs. 69.2%, P < 0.001), quicker axillary dissection (mean 48 vs. 63.2 min, P = 0.004), fewer days of suction drainage (4.3 vs. 5.7 days, P = 0.012), and shorter hospitalization (5.1 vs. 6.5 days, P = 0.021). No difference was found in the rate of hematomas, reoperations or infection. The use of LigaSure in axillary surgery reduced the surgical time and length of hospital stay, favoring early drain removal without increasing postoperative complications.

Usefulness of retropubic tape for recurrent stress incontinence after transobturator tape failure.

INTRODUCTION AND HYPOTHESIS: This study was conducted to evaluate the effectiveness and safety of retropubic suburethral slings (TVT) to treat recurrent stress urinary incontinence (SUI) after transobturator tape (TOT) failure. METHODS: A descriptive study was performed among women with recurrent SUI treated at the Vall d'Hebron University Hospital between January 2006 and December 2009. All women were preoperatively evaluated to rule out complications of the first sling. Urodynamic testing was performed before and after the TOT procedure in all cases. Postoperative follow-up was performed at 1, 6, and 12 months and yearly thereafter. Outcomes were classified as cured, improved, or failed. RESULTS: Twenty-three women were operated on over the study period. The median time to reoperation was 12 months (range 6 to 34 months) and the median follow-up time was 36.1 months (range 7.8 to 60.2 months). Overall cure and improvement rates were 86.4% at 12 and 24 months and 75% at 36 months. Failure was found not to be related to time between both sling surgeries. Two cases of bladder perforation were recorded (8.7%). Postoperative complications were slight and self-limited. De novo urgency occurred in five cases (21.7%). CONCLUSIONS: TVT has been found to be effective to treat recurrent SUI after TOT failure in the present series with slight side effects.