Radiological, pathological and surgical outcomes after neoadjuvant endocrine treatment in patients with ER-positive/HER2-negative breast cancer with a clinical high risk and a low-risk 70-gene signature.

OBJECTIVE: This study aims to evaluate the response to and surgical benefits of neoadjuvant endocrine therapy (NET) in ER+/HER2-breast cancer patients who are clinically high risk, but genomic low risk according to the 70-gene signature (MammaPrint). METHODS: Patients with ER+/HER2-invasive breast cancer with a clinical high risk according to MINDACT, who had a genomic low risk according to the 70-gene signature and were treated with NET between 2015 and 2023 in our center, were retrospectively analyzed. RECIST 1.1 criteria were used to assess radiological response using MRI or ultrasound. Surgical specimens were evaluated to assess pathological response. Two breast cancer surgeons independently scored the eligibility of breast conserving therapy (BCS) pre- and post- NET. RESULTS: Of 72 included patients, 23 were premenopausal (100% started with tamoxifen of which 4 also received OFS) and 49 were postmenopausal (98% started with an aromatase inhibitor). Overall, 8 (11%) showed radiological complete response. Only 1 (1.4%) patient had a pathological complete response (RCB-0) and 68 (94.4%) had a pathological partial response (RCB-1 or RCB-2). Among the 26 patients initially considered for mastectomy, 14 (53.8%) underwent successful BCS. In all 20 clinical node-positive patients, a marked axillary lymph node was removed to assess response. Four out of 20 (20%) patients had a pathological complete response of the axilla. CONCLUSION: The study showed that a subgroup of patients with a clinical high risk and a genomic low risk ER+/HER2-breast cancer benefits from NET resulting in BCS instead of a mastectomy. Additionally, NET may enable de-escalation in axillary treatment.

Real-world data on malignant and borderline phyllodes tumors of the breast: A population-based study of all 921 cases in the Netherlands (1989 -2020).

AIM: The aim of our study is to analyze patterns in treatment and outcome in a population-based series of patients with borderline and malignant phyllodes tumors (PT). MATERIAL AND METHODS: Data on all patients with a borderline or malignant PT (1989-2020) were extracted from the Netherlands Cancer Registry and the Dutch nationwide pathology databank (Palga) and retrospectively analyzed. RESULTS: We included 921 patients (borderline PT n = 452 and malignant PT n = 469). Borderline PT patients more often had breast-conserving surgery (BCS) as final surgery (81 vs. 46%). BCS rates for borderline PT increased over time (OR 1.08 per year, 95%CI 1.04 - 1.13, P < 0.001). In malignant PT adjuvant radiotherapy was given in 14.7%; this rate increased over time (OR 1.07 per year, 95%CI 1.02 - 1.13, P = 0.012). Local recurrence rate (5-year estimate of cumulative incidence) was 8.7% (95%CI 6.0-11.4) for borderline PT and 11.7% (95%CI 8.6-14.8) for malignant PT (P = 0.187) and was related to tumor size ≥ 20 mm (HR 10.6 (95%CI 1.5-76.8) and positive margin (HR 3.0 (95%CI 1.6-5.6), p < 0.001), but not to negative margin width (HR 1.3 ( 95%CI 0.7-2.3), p = 0.350)). Distant metastasis occurred only in malignant PT with a 5-year cumulative incidence of 4.7% (95%CI 3.3 - 6.1). CONCLUSION: This population-based series showed an increase in BCS in borderline PT and an increase in adjuvant radiotherapy in malignant PT over time. We identified malignant PT, BCS, larger tumor size and positive final margins as possible risk factors for local recurrence. Small but negative margins can be accepted.

Management of Benign Phyllodes Tumors: A Dutch Population-Based Retrospective Cohort Between 1989 and 2022.

BACKGROUND: Phyllodes tumors (PTs) are rare tumors of the breast. The current National Comprehensive Cancer Network (NCCN) guidelines recommend excision of benign PTs, accepting close or positive margins. Controversy about the optimal treatment for benign PTs remains, especially regarding the preferred margin width after surgical excision and the need for follow-up evaluation. METHODS: A nationwide retrospective study analyzed the Dutch population from 1989 to 2022. All patients with a diagnosis of benign PT were identified through a search in the Dutch nationwide pathology databank (Palga). Information on age, year of diagnosis, size of the primary tumor, surgical treatment, surgical margin status, and local recurrence was collected. RESULTS: The study enrolled 1908 patients with benign PT. The median age at diagnosis was 43 years (interquartile range [IQR], 34-52 years), and the median tumor size was 30 mm (IQR, 19-40 mm). Most of the patients (95%) were treated with breast-conserving surgery (BCS). The overall local recurrence rate was 6.2%, and the median time to local recurrence was 31 months (IQR, 15-61 months). Local recurrence was associated with bilaterality of the tumor (odds ratio [OR], 4.91; 95% confidence interval [CI], 2.95-28.30) and positive margin status (OR, 2.51; 95% CI 1.36-4.63). The local recurrence rate was 8.9% for the patients with positive excision margins and 4.0% for the patients with negative excision margins. Notably, for 27 patients (22.6%) who experienced a local recurrence, histologic upgrading of the recurrent tumor was reported, 7 (5.9%) of whom had recurrence as malignant lesions. CONCLUSIONS: This nationwide series of 1908 patients showed a low local recurrence rate of 6.2% for benign PT, with higher recurrence rates following positive margins.

Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial.

PURPOSE: The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life. METHODS: In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681). RESULTS: Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND. CONCLUSION: This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.

Internal Mammary Chain Sentinel Nodes in Early-Stage Breast Cancer Patients: Toward Selective Removal.

BACKGROUND: Removal of internal mammary chain sentinel nodes (IMCSNs) affects prognosis and treatment of breast cancer, and internal mammary chain radiotherapy (IMCRT) can improve survival for selected patients. This study aimed to determine the effect of IMCSN biopsy on recurrence-free survival (RFS) and overall survival (OS) and to identify predictive factors for IMCSN and distant metastasis. METHODS: Patients with IMCSNs were selected from a prospective database for the period 1999-2007. Lymphoscintigraphy was performed after intratumoral technetium-99 m injection, and all sentinel nodes were removed. Both RFS and OS were calculated for subgroups with tumor-positive, tumor-negative, or non-removed IMCSNs. Predictive factors were identified for tumor-positive IMCSNs and distant metastasis by regression analysis. RESULTS: For 287 (85%) of 336 patients, IMCSN biopsy was performed, and metastasis was detected in 38 patients (13%). The patients with tumor-positive IMCSNs had poorer OS than the patients with no IMCSN metastasis or non-removed IMCSNs (p = 0.002). These patients also had worse RFS due to distant metastasis (p = 0.002). Axillary metastasis was predictive for tumor-positive IMCSNs (positive predictive value, 38.5%). The predictive factors for distant metastasis were tumor-positive IMCSNs (hazard ratio [HR], 2.5), non-removed IMCSNs (HR, 2.3), tumor diameter greater than 1.5 cm (HR, 3.5), and age older than 65 years (HR, 3.1; reference, < 50 years). CONCLUSIONS: Patients with IMCSNs have worse survival due to distant metastasis. The clinically relevant predictive factor for distant metastasis is tumor larger than 1.5 cm. According to the authors' current protocol, IMCSN biopsy is performed for patients younger than 70 years who have a tumor larger than 1.5 cm, with the cardiotoxicity of the adjuvant IMCRT weighed against the survival benefit.

A Multicentre Evaluation of Risk Factors for Anastomotic Leakage After Restorative Proctocolectomy with Ileal Pouch-Anal Anastomosis for Inflammatory Bowel Disease.

BACKGROUND: Anastomotic leakage is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis [IPAA]. Identification of patients at high risk of leakage may influence surgical decision making. The aim of this study was to identify risk factors associated with anastomotic leakage after restorative proctocolectomy with IPAA. METHODS: Between September 1990 and January 2015, patients who underwent IPAA for inflammatory bowel disease [IBD] were identified from prospectively maintained databases of three tertiary referral centres. Retrospective chart review identified additional data on demographic and surgical variables. Multivariable regression models were developed to identify risk factors for anastomotic leakage. Separate analyses were performed for type of procedure. RESULTS: A total of 640 patients [56.9% male] were included, with a median age of 38 years [interquartile range 29-48]; 96 [15.0%] patients developed anastomotic leakage. Multivariable regression analysis demonstrated that being overweight (body mass index [BMI] > 25], (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.15 - 3.18), and American Society of Anesthesiologists classification [ASA score > 2] [OR 1.91; 95% CI 1.03 - 3.54] were independent risk factors for anastomotic leakage in patients who underwent a completion proctectomy. A disease course of > 5 years [OR 2.34; 95% CI 1.42 - 3.87] and concurrent combination of anti-tumour necrosis factor [TNF] and steroids [OR 6.40; 95% CI 1.76 - 23.20] were independent risk factors for anastomotic leakage in patients who underwent a proctocolectomy and IPAA. CONCLUSIONS: Independent risk factors for anastomotic leakage in IBD patients undergoing IPAA are BMI >25, ASA score >2, disease course > 5 years, and concurrent steroid and anti-TNF treatment, with a different risk profile for one-stage proctocolectomy and completion proctectomy procedures.

The effect of colonoscopic tattooing on lymph node retrieval and sentinel lymph node mapping.

BACKGROUND: In colorectal cancer (CRC), colonoscopic tattooing is performed to mark the tumor site before laparoscopic surgery. OBJECTIVE: To determine whether colonoscopic tattooing can be used to refine staging accuracy by increasing the lymph node (LN) yield per specimen and to determine its accuracy as a sentinel LN procedure. DESIGN: Retrospective, case-control study. All LNs were microscopically examined for the presence of carbon particles. SETTING: A university hospital and a teaching hospital. PATIENTS: A consecutive series of 95 tattooed patients who had surgery for CRC between 2005 and 2009. A series of 210 non-tattooed patients who had surgery in the same time period served as controls. MAIN OUTCOME MEASUREMENTS: Total number of LNs retrieved, detection rate, and sensitivity of tattooing as a sentinel node procedure. RESULTS: A higher LN yield was observed in patients with preoperative tattooing, median (interquartile range) 15 (10-20) versus 12 (9-16), (P = .014). In multivariable analysis, the presence of carbon-containing LNs was an independent predictive factor for a higher LN yield (P = .002). The detection rate was 71%, with a median of 5 carbon-containing LNs per specimen. If preoperative tattooing was used for sentinel node mapping, the overall accuracy of predicting LN status was 94%. In the 24 N1 cases, there were 4 false-negative procedures (sensitivity 83%). LIMITATIONS: Retrospective series. CONCLUSION: After tattooing of CRC, the LN yield was higher than in a control group, and it could be used as a sentinel node procedure with acceptable accuracy rates. Because LN yield and sentinel node mapping are associated with improved diagnostic accuracy of LN involvement, preoperative tattooing can refine staging.

Significantly increased pregnancy rates after laparoscopic restorative proctocolectomy: a cross-sectional study.

OBJECTIVE: To assess the impact of a laparoscopic approach on female fecundity in ileoanal pouch surgery. BACKGROUND: Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) is associated with tubal factor infertility in female patients. Different studies showed less adhesion formation after laparoscopic colectomy. The relation between laparoscopic pouch surgery and fertility, however, has not been studied so far. METHODS: This cross-sectional study was carried out in 3 university hospitals in the Netherlands and in Belgium. Female patients older than 18 years that had IPAA under the age of 41 were eligible for inclusion (n = 179). We sent them a questionnaire addressing medical and fertility history. The primary endpoint was time to first spontaneous pregnancy after IPAA. This study has been registered with ISRCTN.org (ISRCTN85421386). RESULTS: Of 179 eligible patients, 160 (89%) returned the questionnaire. After IPAA, 50 (31%) patients attempted to conceive. Of these, 23 (46%) had undergone open and 27 (54%) had undergone laparoscopic IPAA. Patient characteristics were similar in both groups. Indications for surgery were ulcerative colitis (UC) in 37 patients, familial adenomatous polyposis (FAP) in 12 patients, and colonic ischemia in 1 patient. A Kaplan-Meier survival function was plotted for time to first spontaneous pregnancy and showed a higher pregnancy rate after laparoscopic IPAA (log-rank, P = 0.023). Similarly, subsequent survival analysis for all patients with UC showed an increased pregnancy rate for the laparoscopic group (log-rank, P = 0.033). CONCLUSIONS: Pregnancy rates are significantly higher after laparoscopic IPAA. This makes the laparoscopic approach the method of choice in young women.

Less adhesiolysis and hernia repair during completion proctocolectomy after laparoscopic emergency colectomy for ulcerative colitis.

BACKGROUND: The aim of this study was to determine whether the need for adhesiolysis during completion proctectomy (CP) with ileopouch anal anastomosis (IPAA) is influenced by the surgical approach of the initial emergency colectomy for ulcerative colitis and the hospital setting. METHODS: One hundred consecutive patients who underwent CP with IPAA in our center between January 1999 and April 2010 were included. Emergency colectomy had been performed laparoscopically in 30 of 52 patients at the Academic Medical Center Amsterdam and in 6 of 48 patients at referring hospitals. Case files of these patients were retrospectively reviewed. RESULTS: Significantly more extensive adhesiolysis was performed after open compared to laparoscopic colectomy (47 vs. 6%, P < 0.001). In univariate analysis, emergency colectomy at a referring hospital was also predictive for adhesiolysis (P = 0.003), but the open approach for the initial colectomy was the only independent predictive factor for the need for adhesiolysis (P < 0.001) in a multivariable ordinal logistic regression analysis. Operating time of CP was significantly longer when limited [18 (95% CI = 0-36) min] or extensive [55 (35-75) min] adhesiolysis had to be performed. The interval to CP was longer after open colectomy and after colectomy performed at a referring hospital. Significantly more incisional hernia corrections during CP were performed after open emergency colectomy (14 vs. 0%, P = 0.024). Overall morbidity and postoperative hospital stay of CP were not related to the surgical approach or the hospital setting of the emergency colectomy. CONCLUSION: Laparoscopic as opposed to open emergency colectomy is associated with less adhesiolysis, fewer incisional hernias, and a shorter interval to completion proctectomy.

Quality of life after laparoscopic and open colorectal surgery: a systematic review.

This study was a systematic review of the available evidence on quality of life in patients after laparoscopic or open colorectal surgery. A systematic review was performed of all randomized clinical trials (RCTs) that compared laparoscopic with open colorectal surgery. Study selection, quality assessment and data extraction were carried out independently by two reviewers. Primary endpoint was quality of life after laparoscopic and open colorectal surgery, as assessed by validated questionnaires. The search resulted in nine RCTs that included 2263 patients. Short- and long-term results of these RCTs were described in 13 articles. Postoperative follow-up ranged from 2 d to 6.7 years. Due to clinical heterogeneity, no meta-analysis could be conducted. Four RCTs did not show any difference in quality of life between laparoscopic or open colorectal surgery. The remaining five studies reported a better quality of life in favor of the laparoscopic group on a few quality of life scales at time points ranging from 1 wk to 2 years after surgery. In conclusion, based on presently available high-level evidence, this systematic review showed no clinically relevant differences in postoperative quality of life between laparoscopic and open colorectal surgery.