Using a gene expression signature when controversy exists regarding the indication for adjuvant systemic treatment reduces the proportion of patients receiving adjuvant chemotherapy: a nationwide study.

PURPOSE: The Dutch national guideline advises use of gene-expression signatures, such as the 70-gene signature (70-GS), in case of ambivalence regarding the benefit of adjuvant chemotherapy (CT). In this nationwide study, the impact of 70-GS use on the administration of CT in early breast cancer patients with a dubious indication for CT is assessed. METHODS: Patients within a national guideline directed indication area for 70-GS use who were surgically treated between November 2011 and April 2013 were selected from the Netherlands Cancer Registry database. The effect of 70-GS use on the administration of CT was evaluated in guideline- and age-delineated subgroups addressing potential effect of bias by linear mixed-effect modeling and instrumental variable (IV) analyses. RESULTS: A total of 2,043 patients within the indicated area for 70-GS use were included, of whom 298 received a 70-GS. Without use of the 70-GS, 45% of patients received CT. The 70-GS use was associated with a 9.5% decrease in CT administration (95% confidence interval (CI): -15.7 to -3.3%) in linear mixed-effect model analyses and IV analyses showed similar results (-9.9%; 95% CI: -19.3 to -0.4). CONCLUSION: In patients in whom the Dutch national guidelines suggest the use of a gene-expression profile, 70-GS use is associated with a 10% decrease in the administration of adjuvant CT.Genet Med 18 7, 720-726.Genetics in Medicine (2016); 18 7, 720-726. doi:10.1038/gim.2015.152.

Use of tissue expansion to facilitate liver and small bowel transplant in young children with contracted abdominal cavities.

Liver and small bowel transplant is an established treatment for infants with IFALD. Despite organ reduction techniques, mortality on the waiting list remains high due to shortage of size-matched pediatric donors. Small abdominal cavity volume due to previous intestinal resection poses a significant challenge to achieve abdominal closure post-transplant. Seven children underwent tissue expansion of abdominal skin prior to multiorgan transplant. In total, 17 tissue expanders were placed subcutaneously in seven children. All seven subjects underwent re-exploration to deal with complications: hematoma, extrusion, infection, or port related. Three expanders had to be removed. Four children went on to have successful combined liver and small bowel transplant. Two children died on the waiting list of causes not related to the expander and one child died from sepsis attributed to an infected expander. Tissue expansion can generate skin to facilitate closure of abdomen post-transplant, thus allowing infants with small abdominal volumes to be considered for transplant surgery. Tissue expansion in children with end-stage liver disease and portal hypertension is associated with a very high complication rate and needs to be closely monitored during the expansion process.

The added value of immediate breast reconstruction to health-related quality of life of breast cancer patients.

BACKGROUND: Postmastectomy immediate breast reconstruction (IBR) may improve the quality of life (QoL) of breast cancer patients. Guidelines recommend to discuss the option IBR with all patients undergoing mastectomy. However, substantial hospital variation in IBR-rates was previously observed in the Netherlands, influenced by patient, tumour and hospital factors and clinicians' believes. Information provision about IBR may have a positive effect on receiving IBR and therefore QoL. This study investigated patient-reported QoL of patients treated with mastectomy with and without IBR. METHODS: An online survey, encompassing the validated BREAST-Q questionnaire, was distributed to a representative sample of 1218 breast cancer patients treated with mastectomy. BREAST-Q scores were compared between patients who had undergone mastectomy either with or without IBR. RESULTS: A total of 445 patients were included for analyses: 281 patients with and 164 without IBR. Patients who had received IBR showed significantly higher BREAST-Q scores on "psychosocial well-being" (75 versus 67, p < 0.001), "sexual well-being" (62 versus 52, p < 0.001) and "physical well-being" (77 versus 74, p = 0.021) compared to patients without IBR. No statistically significant difference was found for "satisfaction with breasts" (64 versus 62, p = 0.21). Similar results were found after multivariate regression analyses, revealing IBR to be an independent factor for a better patient-reported QoL. CONCLUSIONS: Patients diagnosed with breast cancer with IBR following mastectomy report a better QoL on important psychosocial, sexual and physical well-being domains. This further supports the recommendation to discuss the option of IBR with all patients with an indication for mastectomy and to enable shared decision-making.

The effect of being informed on receiving immediate breast reconstruction in breast cancer patients.

INTRODUCTION: In previous research from the NABON breast cancer audit, observed hospital variation in immediate breast reconstruction (IBR) rates in the Netherlands could not be fully explained by tumour, patient, and hospital factors. The process of information provision and decision-making may also contribute to the observed variation; the objective of the current study was to give insight in the underlying decision-making process for IBR and to determine the effect of being informed about IBR on receiving IBR. METHODS: A total of 502 patients with IBR and 716 without IBR treated at twenty-nine hospitals were invited to complete an online questionnaire on obtained information and decision-making regarding IBR. The effect of being informed about IBR on receiving IBR was determined by logistic regression analysis. RESULTS: Responses from five hundred and ten patients (n = 229 IBR, n = 281 without IBR) were analysed. Patients with IBR compared to patients without reconstruction showed a difference in patient, tumour, treatment (including radiotherapy), and hospital characteristics. Patients with IBR were more often informed about IBR as a treatment option (99% vs 73%), they discussed (dis)advantages more often with their physician (86% vs 68%), and they were more often involved in shared decision-making (91% vs 67%) compared to patients without IBR. Multivariate logistic regression analysis, corrected for confounders, showed that being informed about IBR increased the odds for receiving IBR fourteen times (p < 0.001). CONCLUSIONS: The positive effect of being informed about IBR on receiving IBR stresses the importance of treatment information in the decision-making process for IBR.

Current decisions on neoadjuvant chemotherapy for early breast cancer: Experts' experiences in the Netherlands.

PURPOSE: To evaluate the opinion of surgical and medical oncologists on neoadjuvant chemotherapy (NAC) for early breast cancer. METHODS: Surgical and medical oncologists (N = 292) participating in breast cancer care in the Netherlands were invited for a 20-question survey on the influence of patient, disease, and management related factors on their decisions towards NAC. RESULTS: A total of 138 surgical and medical oncologists from 64 out of 89 different Dutch hospitals completed the survey. NAC was recommended for locally advanced breast cancer (94%) and for downstaging to enable breast conserving surgery (BCS) (75%). Despite willingness to downstage, 64% of clinicians routinely recommended NAC when systemic therapy was indicated preoperatively. Reported reasons to refrain from NAC are comorbidities (68%), age >70 years (52%), and WHO-performance status ≥2 (93%). Opinions on NAC and surgical management were inconclusive; while 75% recommends NAC to enable BCS, some stated that BCS after NAC increases the risk of a non-radical resection (21%), surgical complications (9%) and recurrence of disease (5%). CONCLUSION: This article emphasizes the need for more consensus among specialists on the indications for NAC in early BC patients. Unambiguous and evidence-based treatment information could improve doctor-patient communication, supporting the patient in chemotherapy timing decision-making.

Patients' experiences with decisions on timing of chemotherapy for breast cancer.

INTRODUCTION: Despite potential advantages, application of chemotherapy in the neo-adjuvant (NAC) instead of adjuvant (AC) setting for breast cancer (BC) patients varies among hospitals. The aim of this study was to gain insight in patients' experiences with decisions on the timing of chemotherapy for stage II and III BC. MATERIALS AND METHODS: A 35-item online questionnaire was distributed among female patients (age>18) treated with either NAC or AC for clinical stage II/III invasive BC in 2013-2014 in the Netherlands. Outcome measures were the experienced exchange of information on the possible choice between both options and patients' involvement in the final decision on chemotherapy timing. Chemotherapy treatment experience was measured with the Cancer Therapy Satisfaction Questionnaire (CTSQ). RESULTS: Of 805 invited patients, 49% responded (179 NAC, 215 AC). NAC-treated patients were younger and more often treated in teaching/academic hospitals and high-volume hospitals. Information on the possibility of NAC was given to a minority of AC-treated patients (AC, stage II:14%, stage III: 31%). Information on pros and cons of both NAC and AC was rated sufficient in about three fourth of respondents. Respondents not always felt having a choice in the timing of chemotherapy (stage II: 54% NAC vs 36% AC; stage III: 26% NAC, 54% AC). CONCLUSION: The need to make a treatment decision on NAC was found to be made explicit in only a small number of adjuvant treated patients, in particular in BC stage II. Less than half of the respondents felt they had a real choice.

Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer: Results of the Dutch national breast cancer audit.

OBJECTIVES: Neoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care. MATERIALS AND METHODS: All patients aged 18-70 years who received surgery for stage III BC from January 2011 to September 2015 were selected from the national multidisciplinary NABON Breast Cancer Audit. Multivariable logistic regression was used to assess independent predictors of NAC use, focussing on hospital factors. RESULTS: A total of 1230 out of 1556 patients with stage III BC (79%) received NAC prior to surgery. The use of NAC did not change over time. We observed a large variation of NAC use between hospitals (0-100%). Age <50 years, breast MRI, large tumour size, advanced nodal disease, negative hormone receptor status and hospital participation in neoadjuvant clinical studies were significant independent predictors of NAC use (all P < 0.001). NAC use in stage III BC was not influenced by hospital type and hospital surgical volume. After adjustment for all independent predictors, variation in NAC use between hospitals remained (0% to 97%). CONCLUSION: NAC was used in 79% of patients with stage III BC, which represent a high quality of care in the NL. Patient, tumour, clinical management and hospital factors could not explain considerable variation in its use between hospitals. Hospital participation in neoadjuvant studies did show to improve the use of NAC in daily practice.

Hospital organizational factors affect the use of immediate breast reconstruction after mastectomy for breast cancer in the Netherlands.

OBJECTIVES: Significant hospital variation in the use of immediate breast reconstruction (IBR) after mastectomy exists in the Netherlands. Aims of this study were to identify hospital organizational factors affecting the use of IBR after mastectomy for ductal carcinoma in situ (DCIS) or invasive breast cancer (BC) and to analyze whether these factors explain the variation. MATERIALS AND METHODS: Patients with DCIS or primary invasive BC treated with mastectomy between 2011 and 2013 were selected from the national NABON Breast Cancer Audit. Hospital and organizational factors were collected with an online web-based survey. Regression analyses were performed to determine whether these factors accounted for the hospital variation. RESULTS: In total, 78% (n = 72) of all Dutch hospitals participated in the survey. In these hospitals 16,471 female patients underwent a mastectomy for DCIS (n = 1,980) or invasive BC (n = 14,491) between 2011 and 2014. IBR was performed in 41% of patients with DCIS (hospital range 0-80%) and in 17% of patients with invasive BC (hospital range 0-62%). Hospital type, number of plastic surgeons available and attendance of a plastic surgeon at the MDT meeting increased IBR rates. For invasive BC, higher percentage of mastectomies and more weekly MDT meetings also significantly increased IBR rates. Adjusted data demonstrated decreased IBR rates for DCIS (average 35%, hospital range 0-49%) and invasive BC (average 15%, hospital range 0-18%). CONCLUSION: Hospital organizational factors affect the use of IBR in the Netherlands. Although only partly explaining hospital variation, optimization of these factors could lead to less variation in IBR rates.

Large variation between hospitals in immediate breast reconstruction rates after mastectomy for breast cancer in the Netherlands.

BACKGROUND: The present study aimed to describe the use of immediate breast reconstruction (IBR) after mastectomy for invasive breast cancer and ductal carcinoma in situ (DCIS) in hospitals in the Netherlands and determine whether patient and tumor factors account for the variation. METHODS: Patients undergoing mastectomy for primary invasive breast cancer or DCIS diagnosed between January 1, 2011 and December 31, 2013 were selected from the NABON Breast Cancer Audit. All the 92 hospitals in the Netherlands were included. The use of IBR in all hospitals was compared using unadjusted and adjusted analyses. Patient and tumor factors were evaluated by univariate and multivariate analyses. RESULTS: In total, 16,953 patients underwent mastectomy: 15,072 for invasive breast cancer and 1881 for DCIS. Unadjusted analyses revealed considerable variation between hospitals in postmastectomy IBR rates for invasive breast cancer (mean 17%; range 0-64%) and DCIS (mean 42%; range 0-83%). For DCIS, younger age and multifocal disease were factors that significantly increased IBR rates. For patients diagnosed with invasive breast cancer, IBR was more often used in younger patients, multifocal tumors, smaller tumors, tumors with a lower grade, absence of lymph node involvement, ductal carcinomas, or hormone-receptor positive/HER2-positive tumors. After case-mix adjustments for these factors, the variation in the use of IBR between hospitals remained large (0-43% for invasive breast cancer and 0-74% for DCIS). CONCLUSIONS: A large variation between hospitals was found in postmastectomy IBR rates in the Netherlands for both invasive breast cancer and DCIS even after adjustment for patient and tumor factors.

Contemporary risks of local and regional recurrence and contralateral breast cancer in patients treated for primary breast cancer.

INTRODUCTION: Breast cancer treatment has evolved extensively over the past two decades with a shift towards less invasive local treatment and increased systemic treatment. The present study aimed to investigate the rates of local (LR) and regional (RR) recurrence and contralateral breast cancer (CBC), evaluating the influence of contributing factors. MATERIALS AND METHODS: We selected all female patients operated for unilateral primary breast cancer (anyTN, M0) between 2003 and 2008 from the Netherlands Cancer Registry. The 5-year risks of developing LR, RR and CBC were estimated using Kaplan-Meier statistics. The influence of various patient, tumour and treatment characteristics was subsequently assessed in multivariable analyses. RESULTS: A total of 52,626 patients were identified. The rates of LR, RR and CBC were 2.7%, 1.5% and 2.9%, respectively. The rates of LR and RR decreased significantly over time in the period 2003-2008, from 3.2% to 2.4% for LR and 1.8 to 1.3% for RR, both becoming lower than the risk of CBC of 2.8%. Multivariable analysis showed that age, tumour size, lymph node involvement, tumour histologic type, grade and hormone receptor status were significant prognosticators for LR and RR, but not for CBC. A trend towards a beneficial effect of breast conserving surgery on LR and RR was seen, while systemic therapy proved to have a protective effect on all three end-points. CONCLUSIONS: In breast cancer patients treated between 2003 and 2008 locoregional recurrence rates decreased and have ended up lower than the risk of developing CBC.