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Background: Randomized trials have shown that axillary clearance (AC) can safely be omitted in patients with sentinel lymph node-positive breast cancer. At the same time, de-escalation of chemotherapy in postmenopausal patients with ER+HER2− breast cancer may depend on detailed axillary nodal stage. The aim of this pre-specified secondary analysis of the SENOMAC trial was to investigate whether the choice of axillary staging affected the proportion of patients receiving adjuvant chemotherapy, and recurrence-free survival (RFS). Methods: Proportion receiving adjuvant chemotherapy was calculated according to AC or sentinel lymph node biopsy (SLNB) only, menopausal status, and region of inclusion, for 2168 patients with clinically node-negative ER+HER2− breast cancer and 1–2 sentinel lymph node macrometastases included in the SENOMAC trial. Findings: In premenopausal patients, 514 out of 615 patients (83.6%) received adjuvant chemotherapy with no significant difference between randomization arms. In postmenopausal patients, the proportion receiving chemotherapy varied considerably by region and country (36.0–82.4%). In Denmark, where 194 out of 539 postmenopausal patients (36.0%) received adjuvant chemotherapy, rates differed significantly between the AC and the SLNB only arm (41.3% vs 31.4%, p = 0.019). After a median follow-up of 44.88 months for Danish postmenopausal patients, no significant difference was seen in 5-year RFS, which was 91% (85.6%–96.6%) for the SLNB only and 90.9% (86.3%–95.6%) for the AC arm (p = 0.42). Interpretation: When omitting axillary clearance, and thus reducing the risk of long-term arm morbidity, potential under-treatment of postmenopausal patients with ER+HER2− breast cancer may require the development of new predictive and imaging tools.

Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.

Purpose: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking. Methods: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents. Results: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types. Conclusions: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors.

Introduction: This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND). Methods: The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1-2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQC30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.

Background/Objective: Sentinel lymph node biopsy (SLNB) is not routine in DCIS. Guidelines suggest SLNB when there is high risk for underlying invasion (large size, high grade, symptomatic lesion) or for detection failure (e.g., after mastectomy). However, guidelines and current practice patterns are inconsistent. Moreover, whilst SLNB is thought to be feasible and accurate after wide local excision (WLE), there is less consensus to support its use after oncoplastic breast-conserving surgery (OPBCS), which can reduce the need for mastectomy (Mx) and is gradually adopted as standard of care. The study aim was to assess if guidelines or individualized assessment result in optimal selection of patients for upfront SLNB. Methods: A panel of 28 international experts (20 surgeons, 8 oncologists, Europe 20, USA 5, Asia/Australia 3) was formed, all blind to the identity of the others. They reviewed anonymized patient cases from the SentiNot study (n=184, m. age 60 years, DCIS m. size 4 cm, Grade 2/3= 36%/64%, mass lesions 13,4%, underlying invasion 24.5%) and answer if they would consider upfront SLNB and why. Consensus and majority were set to >75 and >50%. At the same time, 6 independent raters (4 surgeons, 2 oncologists) reviewed guidelines and assessed the same patient cases per each guideline. Accuracy in relation to underlying invasion was assessed by Receiver Operating Characteristic (ROC) curves and Area Under the Curve (AUC) was reported. Agreement was investigated by kappa statistics and decision-making patterns by logistic multivariate regression and cluster analysis. To allow for flexibility and adaptation to current knowledge, both a frequentist and a Bayesian approach were undertaken. Priors were adjusted after a literature review regarding the factors that are commonly thought to be associated with higher risk for underlying invasion. Results: A total of 44,896 decisions were retrieved and analysed. The panel reached consensus/majority for upfront SLNB

Purpose: To determine the incidence and risk factors of sentinel lymph node (SN) and non-SN metastases in patients with microinvasive breast cancer (MIBC, T1 mic ). This to identify MIBC patients in whom axillary staging can be safely omitted. Methods: The Danish Breast Cancer Group database was used to identify a total of 409 women with breast cancer ≤ 1 mm who underwent sentinel lymph node biopsy (SLNB) between 2002 and 2015. After validation, 233 patients were eligible for the analysis. The incidence rates of SN and non-SN metastases were determined. The associations between clinicopathological variables and a positive SN [pN1, pN1mi, or pN0(i+)] were analyzed using univariate and multivariate designs. Results: Of 233 patients with MIBC, only 9 (3.9%) had SN macrometastases. An additional 18 (7.7%) and 23 (9.9%) had SN micrometastases and isolated tumor cells (ITCs), respectively. Of patients with SN macrometastases, two (22.2%) had non-SN macrometastases. In the adjusted analysis, a positive SN was associated with younger age (P = 0.0001) and a positive human epidermal growth factor 2 receptor (HER2) status (P = 0.03). Conclusions: The low incidence of SN macrometastases < 4% suggests omission of axillary staging in MIBC patients without staging at primary surgery, especially in older (≥ 50 years) HER2 − patients. Still, the relatively high proportion of patients with non-SN macrometastases indicates that axillary treatment might be considered in SN positive patients, especially in younger HER2 + MIBC patients.

OBJECTIVES: Unexplained axillary metastases have been detected in some patients with ductal carcinoma in situ (DCIS), possibly because of occult invasion or iatrogenic tumor cell displacement. The significance of these metastases is unknown and brings into questions the need for upstaging and axillary surgery. What are the risk factors for sentinel lymph node (SN) and non-SN metastases, including the risk of iatrogenic displacement of tumor cells in relation to an excisional biopsy, in patients diagnosed with DCIS?METHODS: Nationwide data on 1787 women diagnosed with DCIS between 2001 and 2015 were retrieved from the Danish Breast Cancer Group database. The association of clinicopathological variables with a positive SN (isolated tumor cells (ITCs), micro- or macrometastases) was evaluated using univariate and multivariate analyses.RESULTS: Of the 1787 patients, 71 (4.0%) had a positive SN: 15 (0.8%) had macrometastases, 42 (2.4%) had micrometastases, and 14 (0.8%) had ITCs. Five patients with a positive SN also had a positive non-SN. In adjusted analysis, a positive SN was associated with younger age (P = 0.036), increased size (P = 0.002), palpability (P = 0.0004) and surgical excisional biopsy (P < 0.001).CONCLUSIONS: The overall risk of a positive SN in patients with DCIS on final pathology is low and less than 9% of these patients had positive non-SNs. This argues against using axillary lymph node dissection in this group. The odds of positive SN after surgical excisional biopsies showed more than a four-fold increase, indicating iatrogenic tumor cell displacement. It is questioned whether these patients should be upstaged and classified as having invasive carcinoma.

INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design.MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive surgery. Sentinel node or diagnostic fine needle aspiration cytology procedure was performed prior to treatment and the women were assessed prior, at two months, and before surgery with clinical examination, mammography and ultrasonography. Surgical specimens were examined for pathological response. Primary outcome was pathological and clinical response.RESULTS: The per protocol population consisted of 112 patients. Clinical response was evaluated in 109 patients and pathological response in 108. Overall a mean decrease in tumor size was 15% (p ≤ .0001). One patient had complete pathological response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment and received neoadjuvant chemotherapy. Eight patients received adjuvant chemotherapy due to lack of response.CONCLUSION: Neoadjuvant aromatase inhibitor therapy is an acceptable strategy in selected postmenopausal patients with ER-rich and HER2-negative early breast cancer with ductal histology and should be considered when chemotherapy either isn't indicated or feasible.

Objectives The risk of axillary metastases in breast cancer patients with only ductal carcinoma in situ (DCIS) is low. Thus, axillary staging with sentinel lymph node biopsy (SLNB) should only be used according to the current guidelines to avoid over-treatment and unnecessary morbidity. In the present study, the use of SLNB in patients with DCIS was evaluated nationally and compared across Danish departments. Material and methods A register-based study was conducted using the Danish Breast Cancer Group database. The use of SLNB in DCIS patients according to year of diagnosis, age at diagnosis, size of lesion, Van Nuys classification, palpability, location and department of surgery was evaluated. The chi-squared test was used to test differences between the groups. Results Data from 2618 Danish female patients diagnosed with DCIS between 2004 and 2015 were included; 54.3% of patients underwent SLNB. The use of SLNB increased from 26.6% in 2004 to 65.1% in 2015. A total of 1877 (71.7%) patients underwent breast-conserving surgery (BCS), and 577 (22.0%) underwent mastectomy, of which 43.9% and 86.0% respectively had a concomitant SLNB. The SLNB was performed in 23.8% of 454 patients not included by the guidelines. The use of SLNB in combination with BCS differed significantly between departments ranging from 19.7% to 63.8%. A significant difference in the use of SLNB with BCS and mastectomy according to department capacity (high-volume departments versus low-volume departments) was observed. Conclusion The use of SLNB in patients with DCIS and adherence to the Danish national guidelines varies among Danish breast surgery departments. To optimise the axillary treatment of patients with DCIS, an improved compliance to the national DCIS guidelines is necessary.

This report describes the case of a patient, who had successful radioactive seed localization (RSL) performed to improve the identification and excision of a renal cell carcinoma. RSL is a new method of preoperative localization, which can ease the surgical procedure, minimize tissue trauma, and ultimately benefit the patient.

BACKGROUND: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison to lumpectomy and mastectomy.MATERIAL AND METHODS: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded.RESULTS: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively), the time from surgery to onset of adjuvant chemotherapy, nor total time from biopsy to the onset of adjuvant chemotherapy (mean time 52.7, 51.9 and 53.2 days, respectively).CONCLUSIONS: Our study shows that oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy in comparison with mastectomy and lumpectomy. Accordingly, patients should not be excluded from treatment with oncoplastic breast surgery due to concerns of delay in adjuvant chemotherapy.

Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79-96% and 49-92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary.

The majority of patients with nonpalpable breast lesions are eligible for breast conserving surgery guided by some kind of lesion localization. The current standard is wire-guided localization (WGL) even though it has several disadvantages, the most important one being the considerable proportion of patients with insufficient resection margin. These patients require a reoperation. New methods in the field of radioguided surgery (RGS) have been developed including radioguided occult lesion localization (ROLL) and radioactive seed localization (RSL). Especially RSL is a very promising technique. Guided by ultrasound a small titanium seed containing typically 1-10 MBq of radioactive iodine-125 is placed in the centre of the nonpalpable breast lesion. During the operation the seed is located with a hand-held gamma probe. To date, only few cohort studies exist on the feasibility of RSL, and the method has only been tested in one randomized trial. The results are either equal to or superior to those obtained with WGL, with regards to achieving free margins and low reoperation rates. Additionally, the RSL technique is less unpleasant for the patient and more flexible regarding preoperative logistics. The seed can be placed a few days before surgery, in contrast to the wire used in WGL, which has to be placed within few hours of surgery. RSL has quickly become popular in surgical and radiological teams that have used the technique and will probably become an important tool for preoperative localization of nonpalpable breast lesions in the near future.

Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79–96% and 49–92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary., SCOPUS: ar.j, info:eu-repo/semantics/published

We estimated the impact of axillary lymph node dissection (ALND) on the risk of axillary recurrence (AR) and overall survival (OS) in breast cancer patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes. We used the Danish Breast Cancer Cooperative Group (DBCG) database to identify patients with micrometastases or ITC in sentinel nodes following surgery for primary breast cancer between 2002 and 2008. A Cox proportional hazard regression model was developed to assess the hazard ratios (HR) for AR and OS between patients with and without ALND. We identified 2074 patients, of which 240 did not undergo further axillary surgery. The 5-year cumulated incidence for AR was 1.58 %. No significant difference in AR was seen between patients with and without ALND. The age adjusted HR for AR if ALND was omitted was 1.79 (95 % CI 0.41-7.80, P = 0.44) in patients with micrometastases and 2.21 (95 % CI 0.54-8.95, P = 0.27), in patients with ITC after a median follow-up of 6 years and 3 months. There was no significant difference in overall survival between patients with and without ALND, when adjusting for age, co-morbidity, tumor size, histology type, malignancy grade, lymphovascular invasion, hormone receptor status, adjuvant systemic treatment and radiotherapy, with a HR for death if ALND was omitted of 1.21 (95 % CI 0.86-1.69, P = 0.27) in patients with micrometastases and 0.96 (95 % CI 0.57-1.62, P = 0.89) in patients with ITC after a medium follow-up on 8 and 5 years. In this nationwide study, we found a low risk of AR on 1.58 % and we did not find a significantly increased risk of AR if ALND was omitted in patients with micrometastases or ITC in sentinel nodes. Furthermore, no significant difference in overall survival was seen between patients with and without ALND when adjusting for adjuvant treatment.