A.C.M. van Bommel

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.

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

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.

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.

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

Background: Aims of the current study were to identify which hospital organizational factors determine the variation in the use of immediate breast reconstruction (IBR) after mastectomy for ductal carcinoma in situ (DCIS) or invasive breast cancer and to investigate whether these factors explain the variation in IBR between hospitals in the Netherlands. Material and Methods: From the NABON Breast Cancer Audit (NBCA) patients with DCIS or primary invasive breast cancer without distant metastatic disease, diagnosed between January 1, 2011 and December 31, 2013 were selected. Hospital organizational factors were identified with an online web-based survey on different organization factors such as the number of weekly multidisciplinary team (MDT) meetings, number of (breast and plastic) surgeons in the hospital and the presence of plastic surgeons in weekly MDT. Logistic regression analyses were used to analyze whether the identified organizational factors significantly affected IBR rates. Patient, tumor and hospital organizational factors that demonstrated to significantly affect IBR rates in univariate analyses were included in the multivariate analyses. Results: In total, 72 hospitals (78% of all Dutch hospitals) participated in the survey. In these hospitals 16,471 female patients were treated with a mastectomy for DCIS (n = 1,980) or non-metastatic breast cancer (n = 14,491) during the study period. In total 20% (n = 3,244) of these patients underwent IBR for DCIS (mean, 42%; hospital range, 0−80%) or invasive breast cancer (mean, 17%; hospital range, 0−62%). Patients who underwent a mastectomy in a teaching (OR=2.6, 95% CI: 1.8−3.7) or university hospital (OR=10.8, 95% CI: 5.7–20.5) or in an intermediate volume (OR=2.0, 95% CI: 1.5−2.8) or high volume hospital (OR=3.0, 95% CI: 2.0−4.5) had a significantly higher chance of receiving IBR compared to patients treated in a district or low volume hospital, respectively. More often IBR was performed in hospitals having 3−4 MDT meetings/week organized compared to hospitals with 1−2 MDT meetings/week (OR=1.4, 95% CI: 1.1−1.8). The number of plastic surgeons in-house did not significantly affect the chance of IBR. In almost 70% of the hospitals, a plastic surgeon structurally attended the weekly MDT meeting, which was prognostic for performing more IBRs compared to MDTs with no or incidental plastic surgeon attendance (OR=3.89, 95% CI: 3.00–5.04). Conclusion: Hospital organizational factors affect the use of IBR and consequently could be subject for improvement to make IBR available to more breast cancer patients.

Abstract P4-02-01: Only in lobular breast cancer MRI use is associated with a lower risk of positive surgical margins and a reduced number of mastectomies. A real-world analysis in The Netherlands

Background The value of magnetic resonance imaging (MRI) for patients with breast cancer remains under debate. Breast MRI may contribute to the planning of local therapy, but also bears the risk of overtreatment. We analyzed the use of MRI and its impact on surgical treatment and risk of detecting contralateral breast cancer in the Netherlands. Patients and methods All patients who underwent primary surgery for stage I-III invasive breast cancer in the years 2011-2013 were identified through the Netherlands Cancer Registry. The following data were documented: year of diagnosis, hospital type and volume, age at diagnosis, clinical T and N stage, histological type and grade, presence of multifocality in resection specimen, hormone receptor status, HER2 status and use of MRI. We analyzed whether MRI use was related to type of surgery (primary or secondary mastectomy or breast conserving surgery), surgical margin involvement, and diagnosis of synchronous contralateral breast cancer. Results MRI was performed in 10,819 (29,8%) out of 36,333 patients newly diagnosed with invasive breast cancer and treated with primary surgery in the years 2011-2013 in the Netherlands. Use of MRI did not clearly increase in this period. In the multivariate analysis, patients younger than 50 years of age compared to patients aged 70 years or older (OR 6.34, 95% CI 5.86-6.87), patients with lobular breast cancer compared to those with ductal carcinoma (OR 3.46; 95% CI 3.23-3.70) and patients with multifocal tumors compared to those without multifocality (OR 2.30, 95% CI 2.15-2.45) were more likely to undergo MRI. Hospital volume ( 150) was only marginally related to MRI use (OR 0.93; 95% CI 0.87-0.99). Patients with invasive breast cancer undergoing MRI were more likely to undergo primary mastectomy than those without MRI (OR 1.21; 95% CI 1.15-1.28), but the subgroup with invasive lobular cancer undergoing MRI were less likely to undergo primary mastectomy (OR 0.85; 95% CI 0.75-0.98). A significantly lower risk of positive surgical margins was seen in patients with lobular breast cancer and breast conserving surgery who had undergone MRI as compared to those without MRI (OR 0.58, 95% CI 0.44-0.78) and, consequently, also a lower risk of secondary mastectomy (OR 0.60, 95% CI 0.41-0.87). Risk of positive surgical margins was not reduced by MRI use in patients with invasive ductal carcinoma (OR 0.91; 95% CI 0.77-1.07). Patients who underwent MRI were almost four times more frequently diagnosed with contralateral breast cancer, compared to those in whom MRI was not performed (OR 3.60, 95% CI 3.06-4.24). Conclusion Breast MRI was significantly more often used in younger patients, patients with lobular and/or multifocal breast cancer. Interestingly, MRI use was associated with less primary and secundary mastectomies in lobular invasive breast cancer, in contrast to an increased number of primary mastectomies in patients with invasive ductal cancer. MRI was further associated with an almost fourfold higher incidence of contralateral breast cancer. Citation Format: Tjan-Heijnen VC, Lobbes MB, Vriens IJ, van Bommel AC, Nieuwenhuijzen GA, Smidt ML, Boersma LJ, van Dalen T, Smorenburg CH, Siesling S, Voogd AC. Only in lobular breast cancer MRI use is associated with a lower risk of positive surgical margins and a reduced number of mastectomies. A real-world analysis in The Netherlands. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-01.