Persistent Pain After Breast Cancer Treatment, an Underreported Burden for Breast Cancer Survivors.

BACKGROUND: Many patients who have undergone surgery experience persistent pain after breast cancer treatment (PPBCT). These symptoms often remain unnoticed by treating physician(s), and the pathophysiology of PPBCT remains poorly understood. The purpose of this study was to determine prevalence of PPBCT and examine the association between PPBCT and various patient, tumor, and treatment characteristics. PATIENTS AND METHODS: We conducted a questionnaire-based cross-sectional study enrolling patients with breast cancer treated at Máxima Medical Center between 2005 and 2016. PPBCT was defined as pain in the breast, anterior thorax, axilla, and/or medial upper arm that persists for at least 3 months after surgery. Tumor and treatment characteristics were derived from the Dutch Cancer Registry and electronic patient files. RESULTS: Between February and March 2019, a questionnaire was sent to 2022 women, of whom 56.5% responded. Prevalence of PPBCT among the responders was 37.9%, with 50.8% reporting moderate to severe pain. Multivariable analyses showed that women with signs of anxiety, depression or a history of smoking had a higher risk of experiencing PPBCT. Women aged 70 years or older at diagnosis were significantly less likely to report PPBCT compared with younger women. No significant association was found between PPBCT and treatment characteristics, including type of axillary surgery and radiotherapy. CONCLUSIONS: A considerable percentage of patients with breast cancer experience PPBCT. Women with signs of anxiety or depression and women with a history of smoking are more likely to report PPBCT. Further research is required to understand the underlying etiology and to improve prevention and treatment strategies for PPBCT.

Screening for distant metastases in patients with ipsilateral breast tumor recurrence: the impact of different imaging modalities on distant recurrence-free interval.

PURPOSE: In patients with ipsilateral breast tumor recurrence (IBTR), the detection of distant disease determines whether the intention of the treatment is curative or palliative. Therefore, adequate preoperative staging is imperative for optimal treatment planning. The aim of this study is to evaluate the impact of conventional imaging techniques, including chest X-ray and/or CT thorax-(abdomen), liver ultrasonography(US), and skeletal scintigraphy, on the distant recurrence-free interval (DRFI) in patients with IBTR, and to compare conventional imaging with 18F-FDG PET-CT or no imaging at all. METHODS: This study was exclusively based on the information available at time of diagnoses of IBTR. To adjust for differences in baseline characteristics between the three imaging groups, a propensity score (PS) weighted method was used. RESULTS: Of the 495 patients included in the study, 229 (46.3%) were staged with conventional imaging, 89 patients (19.8%) were staged with 18F-FDG PET-CT, and in 168 of the patients (33.9%) no imaging was used (N = 168). After a follow-up of approximately 5 years, 14.5% of all patients developed a distant recurrence as first event after IBTR. After adjusting for the PS weights, the Cox regression analyses showed that the different staging methods had no significant impact on the DRFI. CONCLUSIONS: This study showed a wide variation in the use of imaging modalities for staging IBTR patients in the Netherlands. After using PS weighting, no statistically significant impact of the different imaging modalities on DRFI was shown. Based on these results, it is not possible to recommend staging for distant metastases using 18F-FDG PET-CT over conventional imaging techniques.

Low Risk of Development of a Regional Recurrence After an Unsuccessful Repeat Sentinel Lymph Node Biopsy in Patients with Ipsilateral Breast Tumor Recurrence.

BACKGROUND: Unlike sentinel lymph node biopsy (SLNB) in the primary setting, the repeat SLNB (rSLNB) in patients with ipsilateral breast tumor recurrence (IBTR) is challenging, because it is difficult to visualize and/or harvest a sentinel lymph node in every patient. Regional treatments options and safety in terms of regional disease control after such an unsuccessful rSLNB remain unclear. This study assesses factors associated with the performance of axillary lymph node dissection (ALND) after unsuccessful rSLNB and evaluates the occurrence of regional recurrences. METHODS: Data were obtained from the Sentinel Node and Recurrent Breast Cancer (SNARB) study. In 239 patients, the rSLNB was unsuccessful, of whom 60 patients underwent ipsilateral ALND. RESULTS: A shorter time interval between primary treatment and IBTR, and a primary negative SLNB were significantly associated with a higher probability to be treated with ALND after unsuccessful rSLNB (P < 0.001). The 5-year regional-recurrence rate was 0.0% in the ALND group compared with 3.7% in the group treated without ALND (P = 0.113). Of the 179 patients treated without ALND, after a median follow-up of 5.1 years (range 0.3-13.2), 7 (3.9%) developed a regional recurrence as first event after unsuccessful rSLNB. None of the seven recurrences occurred in the ipsilateral axilla. Univariable analysis showed no factors associated with regional recurrence as first event after unsuccessful rSLNB (P > 0.05). CONCLUSIONS: The present study demonstrates that the risk of regional recurrence in patients with an IBTR and an unsuccessful rSLNB is negligible, irrespective of the use of ALND. This suggests that there is no need for additional treatment of the axilla after an unsuccessful rSLNB.

Implementation of a Postoperative Screening and Treatment Guidance for the Low Anterior Resection Syndrome: Preliminary Results.

BACKGROUND: Even years after a low anterior resection, many patients experience persisting bowel complaints. This is referred to as low anterior resection syndrome and has a severe adverse effect on quality of life. Its diverse nature makes it difficult to find a gold-standard therapy for this syndrome. However, most importantly, postoperative guidance appears to be suboptimal. OBJECTIVE: The purpose of this study was to describe and evaluate the implementation of a multimodel guidance with structured screening and treatment options. DESIGN: A retrospective, comparative, cross-sectional study was conducted. Data of patients treated before protocol implementation were compared with a cohort after implementation. SETTINGS: This was a single-center study. PATIENTS: Patients seen after low anterior resection or sigmoid resection between 2010 and 2017 for colorectal malignancy were included. INTERVENTION: This included implementation of a postoperative guidance protocol. MAIN OUTCOME MEASURES: Bowel dysfunction was assessed by the low anterior resection score, whereas the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (C30 and CR29) assessed general and colorectal-specific quality of life. RESULTS: A total of 243 patients were included; 195 were guided before and 48 after protocol implementation. Patients who underwent low anterior resection after protocol implementation showed significantly lower median low anterior resection scores (31 vs 18; p = 0.02) and less major low anterior resection syndrome (51.9% vs 26.3%; p = 0.045). Patients who underwent sigmoid resection did not present with similar changes. Multiple quality-of-life domains showed clinically significant positive changes since our postoperative protocol was implemented. LIMITATIONS: Patient characteristics are not comparable between groups, which makes it difficult to draw firm conclusions. CONCLUSIONS: We recommend that others reconsider their current postoperative management for patients with rectal cancer and suggest a change to a comparable noninvasive, patient-driven postoperative guidance to enhance patient coping mechanisms and self-management and therefore improve their quality of life. See Video Abstract at http://links.lww.com/DCR/A970. IMPLEMENTACIÓN DE UNA GUÍA POSTOPERATORIA DE DETECCIÓN Y TRATAMIENTO PARA EL SÍNDROME DE RESECCIÓN ANTERIOR BAJA: RESULTADOS PRELIMINARES: Incluso años después de una resección anterior baja, muchos pacientes experimentan quejas intestinales persistentes. Esto se conoce como síndrome de resección anterior baja y tiene un efecto adverso grave en la calidad de vida. Su naturaleza diversa hace que sea difícil encontrar una terapia patrón de oro para este síndrome. Pero lo más importante, la guía postoperatoria parece ser subóptima. OBJETIVO: Describir y evaluar la implementación de una guía de múltiples modelos con opciones estructuradas de selección y tratamiento. DISENO: Se realizó un estudio retrospectivo de corte transversal comparativo. Los datos de los pacientes tratados antes de la implementación del protocolo se compararon con una cohorte después de la implementación. MARCO: Centro de estudio único. PACIENTES: Pacientes después de resección anterior baja o resección sigmoidea entre 2010-2017 por neoplasia colorectal. INTERVENCIÓN:: La implementación de un protocolo de guía postoperatoria. PRINCIPALES MEDIDAS DE RESULTADO: La disfunción intestinal se evaluó mediante la puntuación de resección anterior baja, mientras que la Organización Europea para la Investigación y Tratamiento de Cuestionarios de Calidad de Vida del Cáncer (C30 y CR29) evaluó la calidad de vida general y específicamente colorectal. RESULTADOS: Se incluyeron 243 pacientes, 195 fueron guiados antes y 48 después de la implementación del protocolo. Los pacientes que se sometieron a una resección anterior baja después de la implementación del protocolo mostraron puntuaciones de resección anterior bajas medias significativamente más bajas (31 frente a 18; p = 0,02) y menos puntuaciones de síndrome de resección anterior baja (51,9% frente a 26,3%; p = 0,045). Los pacientes sometidos a resección sigmoidea no presentaron cambios similares. Los múltiples dominios de calidad de vida mostraron cambios positivos clínicamente significativos desde que se implementó nuestro protocolo postoperatorio. LIMITACIONES: Las características de los pacientes no son comparables entre los grupos, lo que dificulta sacar conclusiones firmes. CONCLUSIÓNES:: Recomendamos a otros que reconsideren su manejo postoperatorio actual para pacientes con cáncer de recto y sugerimos un cambio a una guía postoperatoria impulsada por el paciente no invasiva comparable para mejorar los mecanismos de afrontamiento y el autocontrol de los pacientes y, por lo tanto, mejorar su calidad de vida. Vea el Video del Resumen en http://links.lww.com/DCR/A970.

Risk of Regional Recurrence After Negative Repeat Sentinel Lymph Node Biopsy in Patients with Ipsilateral Breast Tumor Recurrence.

BACKGROUND: Repeat sentinel lymph node biopsy (rSLNB) has increasingly been used in patients with ipsilateral breast tumor recurrence (IBTR). The safety in terms of regional disease control after this procedure remains unclear. This study evaluates occurrence of regional recurrence as first event in patients with IBTR and negative rSLNB, treated without additional lymph node dissection. PATIENTS AND METHODS: Data were obtained from the Sentinel Node and Recurrent Breast Cancer (SNARB) study. In 201 patients, tumor-negative rSLNB was obtained without performing additional lymph node dissections. RESULTS: With median follow-up of 4.7 (range 0.9-12.7) years, regional recurrence occurred after median time of 3.0 (range 0.4-6.7) years in 4.5% (N = 9) of patients as first event after IBTR and rSLNB. In four of these nine patients, the site of recurrence was in concordance with the anatomical location of rSLNB. Two of the nine recurrences were reported in the ipsilateral axilla, resulting in an ipsilateral axillary regional recurrence rate of 1.0%. In the other seven patients, regional recurrence occurred in aberrant basins. Univariable analysis showed that triple-negative IBTR and lower amount of radioactive-labeled tracer (99mtechnetium) used during rSLNB were associated with developing regional recurrence as first event after negative rSLNB (P < 0.05). CONCLUSIONS: The risk of developing regional recurrence after negative rSLNB is low. The low relapse rate supports the safety of rSLNB as primary nodal staging tool in IBTR. The time has come for clinical guidelines to adopt rSLNB as axillary staging tool in patients with IBTR.

Predicting breast and axillary response after neoadjuvant treatment for breast cancer: The role of histology vs receptor status.

PURPOSE: Neoadjuvant systemic treatment (NST) is increasingly administered in breast cancer patients. This study was conducted to identify predictors for tumor response in the breast and axilla. METHODS: All female patients with nonmetastatic, noninflammatory breast cancer receiving NST between 2003-2013 at the Catharina Cancer Institute in Eindhoven, The Netherlands, were included. RESULTS: The majority of 216 of the 337 patients receiving NST (65%) presented with a cT2 tumor. In 159 patients (47%), the axilla was clinically node positive. A pathologic complete response (pCR) in the breast was achieved in 83 patients (24.6%), and a pCR in the axilla in 65 node-positive patients (40.9%). The triple-negative (OR 4.29, 95% CI 2.15-8.55) and hormone receptor (HR)-negative/HER2-positive tumors (OR 3.73, 95% CI 1.59-8.75) were associated with in-breast pCR. Patients with invasive lobular carcinoma (ILC) were less likely to experience in-breast pCR (OR 0.10, 95% CI 0.01-0.73) than those with invasive ductal cancer. Axillary pCR was found in 65 clinically node-positive patients (41%). Axillary pCR was more likely to occur in HR-positive/HER2-positive (OR 6.24, 95% CI 1.86-20.90) and HR-negative/HER2-positive tumors (OR 6.41, 95% CI 1.95-21.06), compared to HER2-negative disease. In-breast pCR was strongly associated with axillary pCR (OR 10.89, 95% CI 4.20-28.22). CONCLUSION: Response to NST in the breast and axilla is largely determined by receptor status, with high pCR rates occurring in HER2-positive and triple-negative tumors. For axillary pCR, in-breast pCR and HER2-positive disease are the most important predictive factors.

Patterns of Care in the Administration of Neo-adjuvant Chemotherapy for Breast Cancer. A Population-Based Study.

Neo-adjuvant chemotherapy (NAC) is used to facilitate radical surgery for initially irresectable or locally advanced breast cancer. The indication for NAC has been extended to clinically node negative (cN0) patients in whom adjuvant systemic therapy is foreseen. A population-based study was conducted to evaluate the increasing use of NAC, breast conserving surgery (BCS) after NAC and timing of the sentinel node biopsy (SNB). All female breast cancer patients, treated in 10 hospitals in the Eindhoven Cancer Registry area in the Netherlands between January 2003 and June 2012 were included (N = 18,427). In total, 1,402 patients (7.6%) received NAC. The administration increased from 2.5% in 2003 to 13.0% in 2011 (p < 0.001). Use of NAC increased from 0.5% to 2.3% for cT1 tumors, from 2.8% to 27.0% for cT2, from 30.6% to 70.9% for cT3, and from 40.5% to 58.1% for cT4 tumors (p < 0.001). In cN0 patients, use of NAC increased from 1.0% to 4.4% and in clinically node positive patients from 12.0% to 57.5% (p < 0.001). Downsizing of the tumor and BCS are achieved increasingly. In 2011, in three hospitals NAC was administered in <10% of patients, in five hospitals in 10-15% and in two hospitals the proportion of patients receiving NAC was >20% (p < 0.001). Of the 1,402 patients with NAC, 495 patients underwent SNB, 91.5% of whom prior to NAC. In the Netherlands up to one in eight patients receive NAC. The administration of NAC and the percentage of BCS increased over the past decade, especially in cT2 tumors. Considerable hospital variation in the administration of NAC exists.

Repeat sentinel node biopsy in patients with locally recurrent breast cancer: a systematic review and meta-analysis of the literature.

Axillary staging in patients with locally recurrent breast cancer is important for obtaining locoregional control and predicting prognosis. The aim of the present study is to determine technical feasibility, validity, aberrant drainage patterns and clinical consequences of performing repeat sentinel node biopsy (SNB) in these patients. We performed a systematic review and meta-analysis of the literature and included all studies on repeat SNB in locally recurrent breast cancer. A total of 692 patients were described, 301 after a previous SNB, 361 after a previous axillary lymph node dissection (ALND), and 30 with no previous axillary surgery. Sentinel node identification was successful in 452 of the 692 patients (65.3 %), which was significantly higher in patients who had undergone previous SNB compared to previous ALND (81.0 vs. 52.2 %) (P < 0.0001). In 175 of 405 patients with successful lymphatic mapping aberrant drainage pathways were visualized (43.2 %), which were seen more frequently after previous ALND than after previous SNB (69.2 vs. 17.4 %) (P < 0.0001). In 19.2 % of the patients the sentinel node was tumor positive and 27.5 % of these metastases were found in aberrant lymph drainage basins. Overall, 213 patients could be spared an ALND and in 17.9 % of the patients the information derived from the repeat SNB led to a change in adjuvant radiotherapy or systemic treatment plans. The procedure had a false-negative rate of 0.2 %. Repeat SNB is technically feasible and accurate. Next to sparing patients an unnecessary ALND, the information can lead to a change in adjuvant treatment strategy.

Sentinel Node and Recurrent Breast Cancer (SNARB): results of a nationwide registration study.

BACKGROUND: Knowledge of regional lymph node involvement is important in patients with recurrent breast cancer for obtaining better locoregional control and predicting prognosis. To determine technical feasibility, validity, aberrant drainage rates, and clinical consequences of performing repeat sentinel node biopsy (SNB) in patients with locally recurrent breast cancer we conducted the "Sentinel Node and Recurrent Breast Cancer (SNARB)" study. METHODS: A total of 150 patients with locally recurrent breast cancer underwent lymphatic mapping and SNB. In case of an intact axillary lymph node basin, ipsilateral axillary lymph node dissection (ALND) was performed subsequently. RESULTS: A total of 41 patients previously underwent breast conserving therapy (BCT) with SNB, 82 patients BCT with ALND, and 21 patients a mastectomy, of which 9 with SNB and 12 with ALND. In 95 patients (63.3 %) a sentinel node was identified and in 78 patients (52 %) the sentinel node was successfully removed. In 18 patients (22.8 %) a (micro)metastasis was found on pathologic examination. Confirmation ALND in 18 patients showed no axillary lymph node metastases. Aberrant drainage pathways were visualized in 58.9 % of the patients, significantly more frequently after a previous ALND (79.3 %) than after a previous SNB (25.0 %) (P < .0001). Overall, the result of this repeat SNB led to a change in the adjuvant treatment plan in 16.5 % of the patients with a successful repeat SNB. CONCLUSIONS: Repeat SNB is technically feasible and provides reliable results in patients with locally recurrent breast cancer, leading to change in management in 1 of 6 patients.

Oncological and functional outcomes of transanal total mesorectal excision in a teaching hospital in the Netherlands.

PURPOSE: Transanal total mesorectal excision (TaTME) was developed to overcome surgical difficulties experienced in distal pelvic dissection. Concerns have been raised about potential worse postoperative functional outcomes after TaTME. Also, the oncological safety was questioned. This study aimed to describe the functional, surgical, oncological outcomes and quality of life (QoL) after TaTME. METHODS: All consecutive TaTME cases for rectal cancer without disseminated disease between December 2016 and April 2019 were included. The Wexner incontinence score, low anterior resection syndrome (LARS) score, fecal incontinence-related QoL, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-core questionnaire and 29-item module (EORTC QLQ-C30/CR29) were collected. Kaplan-Meier analysis was used to calculate local recurrence-free survival. RESULTS: Thirty patients were eligible for analysis of which 23 received questionnaires. Response rate was 74%. After a median follow-up of respectively 20.0 and 23.0 months for functional and oncological outcomes, the median (interquartile range) of Wexner incontinence and LARS scores were 9.0 (7.0-12.0) and 33.1 (25.0-39.0). Major LARS was present in 73.3%. Fecal incontinence, general and colorectal-specific QoL subdomains that are associated with poor bowel function scored in line with previously reported data. The 2-year actuarial cumulative local recurrence rate was 3.7% (95% confidence interval, 2.4%-5.0%). CONCLUSION: TaTME may lead to significant functional impairments. Patients should receive preoperative counseling on this topic and be fully aware of the potential consequences of their treatment. Oncological data were in line with other short- to moderate-term data and did not show alarming results.

Multifocality in ipsilateral breast tumor recurrence - A study in ablative specimens.

BACKGROUND: The incidence and clinical significance of multifocality in ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) are unclear. With growing interest in repeat BCT, this information has become of importance. This study aimed to gain insight in the incidence of multifocality in IBTR, to identify patient- and tumor-related predicting factors and to investigate the prognostic significance of multifocality. METHODS: Two hundred and fifteen patients were included in this analysis. All had an IBTR after BCT and were treated by salvage mastectomy and appropriate adjuvant therapy. Predictive tumor- and patient-related factors for multifocality in IBTR were identified using X2 test and univariate logistic regression analyses. Prognostic outcomes were calculated using Kaplan Meier analysis and compared using the log rank test. RESULTS: Multifocality was present in 50 (22.9%) of IBTR mastectomy specimens. Axillary positivity in IBTR was significantly associated with multifocality in IBTR. Chest wall re-recurrences occurred more often after multifocal IBTR (14% versus 7% after unifocal IBTR, p = 0.120). Regional re-recurrences did not differ significantly between unifocal and multifocal IBTR (8% vs. 6%, p = 0.773). Distant metastasis after salvage surgery occurred more frequently after multifocal IBTR (15% vs. 24%, p = 0.122). Overall survival was 132 months after unifocal IBTR and 112 months after multifocal IBTR (p = 0.197). CONCLUSION: The prevalence of multifocality in IBTR is higher than in primary breast cancer. Axillary positivity in IBTR was associated with a multifocal IBTR. Chest wall re-recurrences and distant metastasis were, although not statistically significant, more prevalent after multifocal IBTR.