Use of ultrasound and MRI to stage the axilla for breast cancer before and after neoadjuvant chemotherapy prior to targeted sentinel lymphadenectomy.

PURPOSE: Prior data from this Center demonstrated that for patients who had biopsy-proven axillary metastases, were ycN0 after neoadjuvant chemotherapy (NAC), and had a wire-directed (targeted) sentinel lymphadenectomy (WD-SLND), 60% were node negative. The hypothesis of this study was that results of axillary imaging either before or after NAC would be predictive of final pathologic status after WD-SLND. METHODS: For patients treated with NAC between 2015 and 2023, ultrasound and MRI images of the axilla were retrospectively reviewed by radiologists specializing in breast imaging, who were blinded to the surgical and pathology results. RESULTS: Of 113 patients who fit the clinical criteria, 66 (58%) were ypN0 at WD-SLND and 34 (30%) had a pathologic complete response to NAC. There was no correlation between the number of abnormal lymph nodes on pre-NAC ultrasound or MRI imaging and the final pathologic status of the lymph nodes. The positive predictive value (PPV) of abnormal post-NAC axillary imaging was 48% for ultrasound and 53% for MRI. The negative predictive value (NPV) for normal post-NAC axillary imaging was 67% for ultrasound and 68% for MRI. CONCLUSION: The results of axillary imaging were not adequate to identify lymph nodes after NAC that were persistently pathologically node positive or those which had become pathologically node negative.

Enhanced axillary assessment using intradermally injected microbubbles and contrast-enhanced ultrasound (CEUS) before neoadjuvant systemic therapy (NACT) identifies axillary disease missed by conventional B-mode ultrasound that may be clinically relevant.

PURPOSE: The purpose of this study is to measure pre-treatment diagnostic yield of malignant lymph nodes (LN) using contrast-enhanced ultrasound (CEUS) in addition to B-mode axillary ultrasound and compare clinicopathological features, response to NACT and long-term outcomes of patients with malignant LN detected with B-mode ultrasound versus CEUS. METHODS: Between August 2009 and October 2016, NACT patients were identified from a prospective database. Follow-up data were collected until May 2019. RESULTS: 288 consecutive NACT patients were identified; 77 were excluded, 110 had malignant LN identified by B-mode ultrasound (Group A) and 101 patients with negative B-mode axillary ultrasound had CEUS with biopsy of sentinel lymph nodes (SLN). In two cases CEUS failed. Malignant SLN were identified in 35/99 (35%) of B-mode ultrasound-negative cases (Group B). Patients in Group A were similar to those in Group B in age, mean diagnostic tumour size, grade and oestrogen receptor status. More Group A patients had a ductal phenotype. In the breast, 34 (31%) Group A patients and 8 (23%) Group B patients achieved a pathological complete response (PCR). In the axilla, 41 (37%) and 13 (37%) Groups A and B patients, respectively, had LN PCR. The systemic relapse rate was not statistically different (5% and 16% for Groups A and B, respectively). CONCLUSIONS: Enhanced assessment with CEUS before NACT identifies patients with axillary metastases missed by conventional B-mode ultrasound. Without CEUS, 22 (63%) of cases in Group B (negative B-mode ultrasound) may have been erroneously classed as progressive disease by surgical SLN excision after NACT.

Axillary lymph node dissection is not obligatory in breast cancer patients with biopsy-proven axillary lymph node metastasis.

PURPOSE: The ACOSOG Z0011 trial demonstrated that axillary lymph node dissection (ALND) is unnecessary in select patients with cT1-2N0 tumors undergoing breast-conserving therapy with 1-2 positive sentinel lymph nodes (SLNs). However, patients with preoperatively confirmed ALN metastasis were not included and may be subjected to unnecessary ALND. The aim of this study is to identify patients who can be considered for ALND omission when the preoperative ALN biopsy results are positive. METHODS: Breast cancer patients who underwent preoperative ALN biopsy and primary surgery were retrospectively reviewed. Among patients with positive ALN biopsy results, clinicopathological and imaging characteristics were compared according to LN disease burden (1-2 positive LNs vs. ≥ 3 positive LNs). RESULTS: A total of 542 patients were included in the analysis. Among them, 225 (41.5%) patients had a preoperative positive ALN biopsy. More than 40% of the patients (n = 99, 44.0%) with a positive biopsy had only 1-2 positive ALNs. The association between nodal burden and imaging factors was strongest when ≥ 2 suspicious LNs were identified on PET/CT images (HR 8.795, 95% CI 4.756 to 13.262). More than one imaging modality showing ≥ 2 suspicious LNs was also strongly correlated with ≥ 3 positive ALNs (HR 5.148, 95% CI 2.881 to 9.200). CONCLUSIONS: Nearly half of patients with a preoperative biopsy-proven ALN metastasis had only 1-2 positive LNs on ALND. Patients meeting ACOSOG Z0011 criteria with only one suspicious LN on PET/CT or those presenting with few abnormal ALNs on only one imaging modality appear appropriate for SLNB and consideration of ALND omission.

Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride in Non-invasive Axillary Staging in Breast Cancer: Are we Missing a Chance?

BACKGROUND/AIM: In the context of surgical de-escalation in early breast cancer (EBC), this study aimed to evaluate the contrast enhancement ultrasound (CEUS) sentinel lymph node (SLN) procedure as a non-invasive axillary staging procedure in EBC in comparison with standard SLN biopsy (SLNB). PATIENTS AND METHODS: A subanalysis of the AX-CES study, a prospective single-arm, monocentric phase 3 study was performed (EudraCT: 2020-000393-20). The study included patients with EBC undergoing upfront surgery and SLN resection, with no prior history of locoregional treatment, and weighing between 40-85 kg. All patients underwent the CEUS SLN procedure as a non-invasive axillary staging procedure, with CEUS SLN accumulation marked using blue dye. After the CEUS SLN procedure, all patients underwent the standard mapping procedure. Data on success rate, systemic reactions, mean procedure time, mean surgical procedure, mean procedure without axillary staging, CEUS SLN appearance (normal/pathological), SLN number, and concordance with standard mapping procedure were collected. RESULTS: After the CEUS SLN procedure, 29 LNs among 16 patients were identified and marked. In all cases, CEUS SLN revealed at least one LN enhancement. Six (37.50%) LNs were defined as pathological after the CEUS SLN procedure. Definitive staining of CEUS SLN pathology revealed metastatic involvement in four (66.67%) of the cases. Two SLNs were identified during the CEUS SLN procedure; however, owing to the low disease burden, no change in the surgical plan was reported. CONCLUSION: The CEUS SLN procedure shows promise as a technique for non-invasive assessment of the axilla, potentially enabling safe axillary de-escalation in EBC by estimating the axillary disease burden.

Contrast-enhanced Ultrasound Using Intradermal Microbubble Sulfur Hexafluoride for Identification of Sentinel Lymph Nodes During Breast Cancer Surgery: A Clinical Trial.

BACKGROUND/AIM: Sentinel lymph node (SLN) procedures have gained popularity in early breast cancer thanks to the reduction of surgical side-effects. The standard SLN mapping procedure uses 99mTc-nanocolloid human serum albumin with/without blue dye; limitations include logistical challenges and adverse reactions. Recently, contrast-enhanced ultrasound (CEUS) using sulfur hexafluoride has emerged as a promising technique for SLN mapping. Our study aimed to compare the CEUS technique with the standard isotope method. MATERIALS AND METHODS: AX-CES, a prospective, monocentric, single-arm phase-3 study was designed (EudraCT: 2020-000393-20). Inclusion criteria were histologically diagnosed early breast cancer eligible for upfront surgery and SLN resection, bodyweight 40-85 kg, and no prior history of ipsilateral surgery or radiotherapy. All patients underwent CEUS prior to surgery and blue dye injection was performed in areas with contrast accumulation. After the experimental procedure, all patients underwent the standard mapping procedure and SLN frozen section assessment was performed. Data on the success rate, systemic reactions, mean procedure time, CEUS appearance, SLN number, and concordance with standard mapping procedure were collected. RESULTS: Among 16 cases, a median of two SLNs were identified during CEUS. In all cases, at least one SLN was identified by CEUS (100%). In six cases, SLNs were classified during CEUS as abnormal, which was confirmed by definitive staining in four cases. After the standard mapping technique, in 15 out of the 16 cases (87.50%), at least one SLN from the standard mapping procedure was marked with blue dye in the CEUS procedure. In our series, sensitivity and specificity of SLN detection by CEUS were 75% and 100%, respectively. CONCLUSION: CEUS is a safe and manageable intraoperative procedure. When compared with standard techniques, US appearance during CEUS may provide additional information when associated with histological assessment.

Innovative approach to lymphadenectomy in breast sarcoma.

Lymphatic dissemination is thought to be a rare event in breast sarcomas. The decision to perform axillary clearance is challenging. In our prospective cohort, we aimed to evaluate the frequency and factors determining lymph node (LN) involvement in breast sarcomas, with the aim of proposing a decision tree/algorithm for the realization of LN clearance in breast sarcomas. PATIENTS AND METHODS: Fourty-five women were surgically treated for breast sarcomas from 1982 to 2020. Angiosarcomas and other sarcomas were compared in terms of LN involvement, recurrence, and mortality. RESULTS: Twenty-three patients underwent axillary lymphadenectomy. Initial LN involvement was diagnosed in one case of D2-40 positive, primary angiosarcoma for which preoperative imaging detected a suspicious LN confirmed by preoperative histology. Among the 22 patients who had no initial axillary lymphadenectomy, two patients with D2-40 positive angiosarcoma had recurrent cancer in LN (internal mammary group in 1 and homolateral axilla in 1). The average follow-up in the overall population was 6.2 years (±8.3). The cohort's overall recurrence rate was 33% (15/45) and the time of recurrence after initial surgery was on average 2.4 years (±3.1). For the three patients with LN metastases, time to recurrence after surgery was 3.7 years (±4.5). There was no significant difference in the overall recurrence rate depending on whether or not lymphadenectomy was initially performed (respectively 26% vs 41% OR=1.11, P=0.29). DISCUSSION/CONCLUSION: Systematic axillary clearance leads to overtreatment in breast sarcomas. A decision tree, including radiological examination of the axilla, histological type of sarcoma, and D2-40 positivity, could be a decision aid in the choice of axillary clearance.

To Look or Not to Look? Axillary Imaging: Less May Be More.

Axillary lymph node status in patients with breast cancer is an important prognostic indicator and often guides vital treatment decisions. Although in many cases imaging plays a crucial role in the assessment of the axilla, it is essential that targeted axillary US and/or image-guided biopsy of an axillary lymph node be performed by the radiologist only when clinically appropriate. This decision-making process requires multidisciplinary communication and collaboration among radiologists, surgeons, medical oncologists, and radiation oncologists. Our goal is to review axillary imaging for patients with breast cancer in two distinct clinical settings, the patient with newly diagnosed breast cancer who meets American College of Surgeons Oncology Group Z0011 criteria and patients undergoing neoadjuvant chemotherapy, with a specific focus on potential reasons to not perform axillary US and/or image-guided biopsy in these settings.

Feasibility and Oncological Safety of Axillary Reverse Mapping in Patients With Locally Advanced Breast Cancer and Partial Response After Neoadjuvant Chemotherapy.

BACKGROUND/AIM: Axillary reverse mapping (ARM) aims to identify and preserve arm drainage in order to prevent lymphedema following axillary lymph node dissection. Oncological-safety and feasibility are still debated, especially in patients with locally-advanced breast cancer (LABC). We report the first case of the AXMAP 1.0 study performed in our Institution. PATIENTS AND METHODS: A 52-year-old patient with a triple-negative LABC and partial response to neoadjuvant chemotherapy underwent axillary lymph-node dissection using fluorescence ARM. RESULTS: Two lymph-nodes draining the ipsilateral upper arm were identified and were not preserved due to suspicion of malignancy. Pathological examination confirmed the presence of malignancy in both lymph nodes. CONCLUSION: Further studies should be designed in order to validate the oncological safety of this technique, especially in patients with LABC requiring neoadjuvant chemotherapy.