An analysis of complication rates and the influence on patient satisfaction and cosmetic outcomes following oncoplastic breast surgery.

INTRODUCTION: This study aimed to evaluate complication rates, patient satisfaction, and cosmetic outcomes after oncoplastic breast-conserving surgery (OPS). Furthermore, outcome differences between volume displacement and volume replacement techniques and the effect of postoperative complications on outcomes were evaluated. METHODS: This was a prospective single-center study addressing patients who underwent OPS from 2017 to 2020. The BREAST-Q was used to measure patient satisfaction, and cosmetic outcomes were assessed by patient self-evaluation and panel evaluation based on medical photographs. RESULTS: A total of 75 patients were included. The overall complication rate was 18.7%, of which 4% required invasive interventions. Median BREAST-Q scores ranged from 56 to 100 and cosmetic outcomes were scored good to excellent in 60-86%. No differences in complications were observed between volume replacement and volume displacement techniques. Following volume displacement techniques, patients-reported higher BREAST-Q scores for the domain "physical well-being of the chest" and lower cosmetic outcomes scores for "mammary symmetry." Patients with complications scored significantly lower on several domains of the BREAST-Q and in various cosmetic outcome categories. CONCLUSION: In this cohort, an overall complication rate of 18.7% was observed. Patients were generally satisfied, and most cosmetic outcomes were good to excellent. Volume displacement or replacement techniques were performed for different indications and generally showed comparable results. Expected differences in physical discomfort and symmetry between both techniques were observed. In addition, the occurrence of complications resulted in lower patient satisfaction and cosmetic outcomes. These findings emphasize the importance of thorough preoperative counselling.

Effect of physical exercise on cognitive function after chemotherapy in patients with breast cancer: a randomized controlled trial (PAM study).

BACKGROUND: Up to 60% of breast cancer patients treated with chemotherapy is confronted with cognitive problems, which can have a significant impact on daily activities and quality of life (QoL). We investigated whether exercise training improves cognition in chemotherapy-exposed breast cancer patients 2-4 years after diagnosis. METHODS: Chemotherapy-exposed breast cancer patients, with both self-reported cognitive problems and lower than expected performance on neuropsychological tests, were randomized to an exercise or control group. The 6-month exercise intervention consisted of supervised aerobic and strength training (2 h/week), and Nordic/power walking (2 h/week). Our primary outcome was memory functioning (Hopkins Verbal Learning Test-Revised; HVLT-R). Secondary outcomes included online neuropsychological tests (Amsterdam Cognition Scan; ACS), self-reported cognition (MD Anderson Symptom Inventory for multiple myeloma; MDASI-MM), physical fitness (relative maximum oxygen uptake; VO2peak), fatigue (Multidimensional Fatigue Inventory), QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; EORTC QLQ C-30), depression (Patient Health Questionnaire-9, Hospital Anxiety and Depression Scale; HADS), and anxiety (HADS). HVLT-R total recall was analyzed with a Fisher exact test for clinically relevant improvement (≥ 5 words). Other outcomes were analyzed using multiple regression analyses adjusted for baseline and stratification factors. RESULTS: We randomized 181 patients to the exercise (n = 91) or control group (n = 90). Two-third of the patients attended ≥ 80% of the exercise sessions, and physical fitness significantly improved compared to control patients (B VO2peak 1.4 ml/min/kg, 95%CI:0.6;2.2). No difference in favor of the intervention group was seen on the primary outcome. Significant beneficial intervention effects were found for self-reported cognitive functioning [MDASI-MM severity (B-0.7, 95% CI - 1.2; - 0.1)], fatigue, QoL, and depression. A hypothesis-driven analysis in highly fatigued patients showed positive exercise effects on tested cognitive functioning [ACS Reaction Time (B-26.8, 95% CI - 52.9; - 0.6) and ACS Wordlist Learning (B4.4, 95% CI 0.5; 8.3)]. CONCLUSIONS: A 6-month exercise intervention improved self-reported cognitive functioning, physical fitness, fatigue, QoL, and depression in chemotherapy-exposed breast cancer patients with cognitive problems. Tested cognitive functioning was not affected. However, subgroup analysis indicated a positive effect of exercise on tested cognitive functioning in highly fatigued patients. Trial Registration Netherlands Trial Registry: Trial NL5924 (NTR6104). Registered 24 October 2016, https://www.trialregister.nl/trial/5924 .

Predicting postoperative complications and their impact on quality of life and functional status in older patients with breast cancer.

BACKGROUND: The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). METHODS: Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. RESULTS: The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. CONCLUSION: This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders.

Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.

De-escalation of axillary surgery in breast cancer patients treated in the neoadjuvant setting: a Dutch population-based study.

PURPOSE: An overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST). METHODS: Patients with cT1-4N0-3 breast cancer treated with NST (2006-2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients. RESULTS: A total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 (p < 0.001). SLNB performed post-NST increased from 33 to 62% (p < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 (p < 0.001). Age (OR 1.01, CI 1.00-1.02), year of diagnosis (OR 0.47, CI 0.44-0.50), HER2-positive disease (OR 0.62, CI 0.52-0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06-1.65, T3 vs. T1 OR 2.04, CI 1.58-2.63, T4 vs. T1 OR 6.37, CI 4.26-9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28-2.12) were correlated with performing ALND in cN+ patients. CONCLUSIONS: ALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists.

INTRODUCTION: Various options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists. MATERIALS AND METHODS: A survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST. RESULTS: A total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND. CONCLUSION: Current axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.

Excision of both pretreatment marked positive nodes and sentinel nodes improves axillary staging after neoadjuvant systemic therapy in breast cancer.

BACKGROUND: Marking the axilla with radioactive iodine seed and sentinel lymph node (SLN) biopsy have been proposed for axillary staging after neoadjuvant systemic therapy in clinically node-positive breast cancer. This study evaluated the identification rate and detection of residual disease with combined excision of pretreatment-positive marked lymph nodes (MLNs) together with SLNs. METHODS: This was a multicentre retrospective analysis of patients with clinically node-positive breast cancer undergoing neoadjuvant systemic therapy and the combination procedure (with or without axillary lymph node dissection). The identification rate and detection of axillary residual disease were calculated for the combination procedure, and for MLNs and SLNs separately. RESULTS: At least one MLN and/or SLN(s) were identified by the combination procedure in 138 of 139 patients (identification rate 99·3 per cent). The identification rate was 92·8 per cent for MLNs alone and 87·8 per cent for SLNs alone. In 88 of 139 patients (63·3 per cent) residual axillary disease was detected by the combination procedure. Residual disease was shown only in the MLN in 20 of 88 patients (23 per cent) and only in the SLN in ten of 88 (11 per cent), whereas both the MLN and SLN contained residual disease in the remainder (58 of 88, 66 per cent). CONCLUSION: Excision of the pretreatment-positive MLN together with SLNs after neoadjuvant systemic therapy in patients with clinically node-positive disease resulted in a higher identification rate and improved detection of residual axillary disease.

ANTECEDENTES: En el cáncer de mama con ganglios positivos clínicamente tras el tratamiento neoadyuvante sistémico, se ha propuesto la utilización de iodo radioactivo (Marking Axilla with Radioactive Iodine, MARI) y de la biopsia de ganglio linfático centinela para la estadificación axilar. En este estudio se evaluó la tasa de identificación y detección de enfermedad residual cuando se combinó la exéresis de los ganglios linfáticos marcados antes del tratamiento (marked lymph nodes, MLN) junto con los ganglios centinela (sentinel lymph nodes, SLN). MÉTODOS: Se realizó un análisis retrospectivo multicéntrico de pacientes con cáncer de mama con ganglios positivos clínicamente que se sometieron a tratamiento neoadyuvante sistémico y en las que se combinaron ambas técnicas (con o sin disección axilar). Se calcularon las tasas de identificación y detección de enfermedad residual axilar para MLN y SLN por separado y en conjunto. RESULTADOS: En 138/139 pacientes se identificaron ≥ 1 MLN y/o SLN combinando ambas técnicas (tasa de identificación del 99,3%). La tasa de identificación fue de 92,8% para MLN y del 87,8% para SLN. Combinando ambas técnicas se detectó enfermedad axilar residual en 88/139 (63,3%) pacientes. Se detectó enfermedad residual en 20/88 (22,7%) pacientes utilizando únicamente MLN, en 10/88 (11,4%) pacientes utilizando únicamente SLN y en 58/88 (65,9%) combinando ambas técnicas. CONCLUSIÓN: La exéresis conjunta de los ganglios marcados con iodo radioactivo antes del tratamiento neoadyuvante sistémico y de los ganglios centinela después del tratamiento en pacientes con cN+ logró una tasa de identificación más alta y una mejor detección de la enfermedad axilar residual.

Prognosis of residual axillary disease after neoadjuvant chemotherapy in clinically node-positive breast cancer patients: isolated tumor cells and micrometastases carry a better prognosis than macrometastases.

PURPOSE: The aim of this study was to compare disease-free survival (DFS) and overall survival (OS) between clinically node-positive breast cancer patients, treated with neoadjuvant chemotherapy (NAC), with axillary pathologic complete response (ypN0), residual axillary isolated tumor cells or micrometastases (ypNitc/mi), and residual axillary macrometastases (ypN1-3). METHODS: All patients diagnosed with clinically node-positive primary invasive breast cancer treated with NAC and subsequent axillary lymph node dissection between 2005 and 2008 were retrospectively analyzed. Data were obtained from the Netherlands Cancer Registry. Patients were stratified by final pathological axillary status: ypN0, ypNitc/mi, or ypN1-3. The main outcome measures DFS and OS were analyzed using Kaplan-Meier survival analysis. Uni- and multivariable cox regression analyses were used to determine independent predictors for DFS and OS. RESULTS: A total of 1347 patients were included. Pathologic nodal status was ypN0 in 22.2%, ypNitc/mi in 3.8%, and ypN1-3 in 74.0% of patients. Overall, 5-year DFS was 57.8% and mean OS was 7.4 years. DFS and OS were comparable between ypN0 and ypNitc/mi (HR 1.38 (0.40-4.79, p = 0.613) and HR 0.92 (0.27-3.09, p = 0.889), respectively), but significantly different between ypN0 and ypN1-3 (HR 1.78 (1.06-3.00, p = 0.031) and HR 1.70 (1.07-2.71, p = 0.026), respectively). CONCLUSIONS: Clinically node-positive patients, treated with NAC, with axillary nodal status ypN0 or ypNitc/mi carry similar prognosis regarding DFS and OS. Axillary nodal status ypN1-3 is associated with a less favorable prognosis. Future studies should consider ypN0 and ypNitc/mi as one entity.

Interventional ductoscopy in patients with pathological nipple discharge.

BACKGROUND: Surgery is the intervention of choice for definitive diagnosis and treatment in women with pathological nipple discharge (PND). Ductoscopy has been reported to improve diagnosis, but as an interventional procedure it may also reduce the need for surgery. This study evaluated interventional ductoscopy in patients with PND. METHODS: A prospective study on ductoscopy was conducted in consecutive patients with PND, but without a suspected malignancy on routine diagnostic evaluation. Intraductal lesions were removed by ductoscopic extraction. Surgery was undertaken if there were suspicious ductoscopic findings or at the patient's request. Therapeutic efficacy was determined by cannulation success, detection and removal rates, symptom resolution and avoided surgery. RESULTS: Ductoscope introduction was successful in 71 (87 per cent) of 82 patients, with abnormalities visualized in 53 (65 per cent); these were mostly polypoid lesions (29 patients). The lesion was removed in 27 of 34 attempted ductoscopic extractions. Twenty-six (32 per cent) of the 82 patients underwent surgery, whereas surgery was avoided in 56 (68 per cent). After a median follow-up of 17 (range 3-45) months, 40 patients (49 per cent) no longer experienced symptoms of PND, 13 of 34 patients experienced an insufficient therapeutic effect after attempted ductoscopic extraction, and the outcome was unknown in two (2 per cent). Malignancy was diagnosed in four patients (5 per cent); two had been missed at ductoscopy and two at initial surgery after ductoscopy. CONCLUSION: Interventional ductoscopy is technically feasible and may help to avoid surgery in the majority of patients. As endoscopic removal of intraductal lesions is not always possible and malignancy can be the underlying cause of PND, ductoscopic instruments should be further optimized to allow definitive histological diagnosis.

Impact of preoperative evaluation of tumour grade by core needle biopsy on clinical risk assessment and patient selection for adjuvant systemic treatment in breast cancer.

BACKGROUND: Histological characteristics are important when making a decision on adjuvant systemic treatment in breast cancer. Preoperative assessments of core needle biopsy (CNB) specimens are becoming increasingly relevant as novel minimally invasive ablative techniques are introduced, because a surgical specimen is no longer obtained with these methods. The clinical impact of potential underestimation of tumour grade on preoperative CNB on clinical decision-making was evaluated. METHODS: Histological tumour grade was reassessed on CNB and resection specimens from consecutive invasive ductal carcinomas diagnosed between 2010 and 2013. For each patient, the indication for systemic therapy was assessed, based on either CNB or surgical excision, in combination with clinical characteristics and imaging findings. The clinical impact of discordance between tumour grade on CNB versus the resection specimen was assessed. RESULTS: The analysis included 213 invasive ductal carcinomas in 199 patients. Discordance in tumour grade between CNB and the resection specimen was observed in 64 (30.0 per cent) of 213 tumours (κ = 0.53, 95 per cent c.i. 0.43 to 0.63). A decision on adjuvant treatment based on CNB would have resulted in overtreatment in seven (3.5 per cent) and undertreatment in three (1.5 per cent) of 199 patients. In the undertreated patients, incorrect omission of adjuvant systemic treatment would have increased the predicted 10-year mortality rate by 2.6-5.2 per cent and 10-year recurrence rate by 8.2-15.3 per cent based on the online risk assessment tool Adjuvant! CONCLUSION: The substantial discordance in tumour grading between CNB and resection specimens from breast cancer affects the indication for adjuvant therapy in only a small minority of patients with invasive ductal carcinoma. Assessment of tumour grade by CNB is feasible and accurate for the planning of postoperative treatment.

Sentinel lymph node localization with contrast-enhanced ultrasound and an I-125 seed: an ideal prospective development study.

INTRODUCTION: Our aim was to evaluate the development of microbubble-enhanced sentinel lymph node (SLN) localization with placement of an I-125 seed in breast cancer patients as a potential alternative for SLN localization with nanocolloid. The study is conducted and reported following the IDEAL recommendations for evaluation of a new technique at Stage 2a (Prospective Development Study). METHODS: Fourteen consecutive patients with 15 lesions underwent microbubble-enhanced SLN localization with placement of an I-125 seed after the standard SLN localization (nanocolloid). We placed an I-125 seed within or near the SLN following its identification using intradermally injected microbubbles. The SLN was excised guided by nanocolloid and the SLN containing the I-125 seed was searched for. All technical modifications are described and standardized outcomes measured. RESULTS: Twelve (80%) microbubble procedures with I-125 seed placements were technically successful. In three cases no microbubble-enhancing lymph node could be detected. Intraoperatively, we found nine I-125 seeds within 0.5 cm of the nanocolloid confirmed SLN. One I-125 seed was found next to a non-SLN and two I-125 seeds were not near any lymph node. Overall, the procedure was successful in 60% (9 out of 15) of the cases. CONCLUSION: Given the low success rate, we conclude that microbubble-enhanced SLN is not a viable alternative to the standard SLN procedure. Modifications to this technique did not improve its performance. Planned study (NTR3690 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3690) was stopped early due to this conclusion and results reported in order to provide a full and transparent record of the evolution of technique.

"Axillary recurrences after sentinel lymph node biopsy: a multicentre analysis and follow-up of sentinel lymph node negative breast cancer patients".

INTRODUCTION: The objective of this study was to conduct a multicentre data analysis to identify prognostic factors for developing an axillary recurrence (AR) after negative sentinel lymph node biopsy (SLNB) in a large cohort of breast cancer patients with long follow-up. PATIENTS AND METHODS: The prospective databases from different hospitals of clinically node negative breast cancer patients operated on between, 2000 and 2002 were analyzed. SLNB was performed and pathological analysis done by local pathologists according to national guidelines. Adjuvant treatment was given according to contemporary guidelines. Multivariate analysis was performed using all available variables, a p-value of <0,05 was considered to be significant. RESULTS: A total of 929 patients who did not undergo axillary lymph node dissection were identified. After a median follow up of 77 (range 1-106) months, fifteen patients developed an isolated AR (AR rate 1,6%). Multivariate analysis showed that young age (p = 0.007) and the absence of radiotherapy (p = 0.010) significantly increased the risk of developing an AR. Distant metastasis free survival (DMFS) was significantly worse for patients with an AR compared to all other breast cancer patients (p < 0,0001). CONCLUSION: Even after long-term follow up, the risk of developing an AR after a negative SLN in breast cancer is low. Young age and absence of radiation therapy are highly significant factors for developing an axillary recurrence. DMFS is worse for AR patients compared to patients initially diagnosed with N0 or N1 disease.

[Potential cornea, heart valve, bone and skin donors in 5 Dutch hospitals far outnumber actual donors]. / Aantal potentiële hoornvlies-, hartklep-, bot- en huiddonors in vijf Nederlandse ziekenhuizen veel groter dan aantal daadwerkelijke donors.

OBJECTIVE: To determine the number of potential cornea, heart valve, bone and skin donors among patients who died in Dutch hospitals, in comparison with the number of actual donors. DESIGN: Descriptive. SETTING: Five hospitals in the western part of the Netherlands. MATERIAL AND METHODS: The medical records of patients who died in 1989 were reviewed. Children younger than 4 weeks were excluded from the study. On the basis of criteria used by the Eurotransplant and Bio Implant Services Foundations and those of the skin bank of the Dutch Burns Foundation, it was determined if the deceased were medically suitable as cornea, heart valve, bone or skin donor. RESULTS: Data were collected on 2150 of 2369 deceased (90.8%), mean age 69.5 (17.0) (SD) years. Medical criteria for cornea donation were met in 72% of the cases, 6.8% of these became actual donors. The figures for heart value donors were 4.3% and 9.7% respectively, and for bone donors 2.7% and 0%. The percentage of potential skin donors could not be determined, because essential data were missing from the medical records. After extrapolation the number of donors among all patients who died in Dutch hospitals in 1989 amounted to 35,046 potential cornea donors, 2,093 potential heart valve donors and 1,314 potential bone donors. CONCLUSION: Only a very small proportion of the potential tissue donors were referred to Eurotransplant and Bio Implant Services. Therefore, waiting lists for tissue transplantation are not necessary.