L. de Munck

Surgical treatment of early stage breast cancer in elderly: an international comparison

Over 40% of breast cancer patients are diagnosed above the age of 65. Treatment of these elderly patients will probably vary over countries. The aim of this study was to make an international comparison (several European countries and the US) of surgical and radiation treatment for elderly women with early stage breast cancer. Survival comparisons were also made. Data were obtained from national or regional population-based registries in the Netherlands, Switzerland, Ireland, Belgium, Germany, and Portugal. For the US patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Early stage breast cancer patients aged ≥65 diagnosed between 1995 and 2005 were included. An international comparison was made for breast and axillary surgery, radiotherapy after breast conserving surgery (BCS), and relative or cause-specific survival. Overall, 204.885 patients were included. The proportion of patients not receiving any surgery increased with age in many countries; however, differences between countries were large. In most countries more than half of all elderly patients received breast conserving surgery (BCS), with the highest percentage in Switzerland. The proportion of elderly patients that received radiotherapy after BCS decreased with age in all countries. Moreover, in all countries the proportion of patients who do not receive axillary surgery increased with age. No large differences in survival between countries were recorded. International comparisons of surgical treatment for elderly women with early stage breast cancer are scarce. This study showed large international differences in treatment of elderly early stage breast cancer patients, with the most striking result the large proportion of elderly who did not undergo surgery at all. Despite large treatment differences, survival does not seem to be affected in a major way.

Quality improvement by implementing an integrated oncological care pathway for breast cancer patients

BACKGROUND AND AIM In cancer care, more and more systemized approaches such as care pathways are used to reduce variation, reduce waiting- and throughput times and to improve quality of care. The aim of this study was to determine whether the implementation of a multidisciplinary breast cancer pathway in three hospitals has improved the care for breast cancer patients. METHODS Retrospectively almost 800 patients with breast cancer were selected from the Netherlands Cancer Registry (NCR). The patients were divided in two groups: before implementation of the pathway in 2006-07 (baseline measurement) and those after implementation in 2009 (post measurement). Fourteen quality indicators were compared before and after the implementation of the care pathway. To estimate the impact of the care pathway relative to evidence based guidelines and profession-based norms, involved project leaders were interviewed. RESULTS Seven out of eight indicators with medical information and four out of five indicators with information about waiting- and throughput times improved. With the multidisciplinary meeting as key in the breast cancer care, more compliance to national guidelines was observed. E.g. for more patients a HER2neu test was performed after implementation of the pathway (from 92% to 96%, ⤳ = 0.016) and more patients started with their first chemotherapy (from 33% to 45%) or their first radiotherapy (from 55% to 59%) within 4 weeks after surgery. CONCLUSION Implementing a multidisciplinary breast cancer pathway leads to better compliance with the national guidelines and can improve breast cancer care.

Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients: Identification rate and influence on axillary treatment

The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The Netherlands. Patients diagnosed with clinically node negative primary breast cancer between 1st January 2010 and 30th June 2013 who received NAC and SNB were selected from the Netherlands Cancer Registry. Data on patient and tumour characteristics, axillary staging and treatment were analysed. Two groups were defined: (1) patients with SNB before NAC (N=980) and (2) patients with SNB after NAC (N=203). Eighty-three percent of patients underwent SNB before NAC, with large regional variation (35-99%). The SN identification rate differed for SNBs conducted before and after NAC (98% versus 95%; p=0.032). A lower proportion of patients had a negative SNB when assessed before NAC compared to after (54% versus 67%; p=0.001). The proportion of patients receiving any axillary treatment was higher for those with SNB before NAC than after (45% versus 33%; p=0.006). In conclusion, variation exists in the timing of SNB in clinical practice in The Netherlands for clinically node negative breast cancer patients receiving NAC. The post-NAC SN procedure is, despite some lower SN identification rate, associated with a significantly less frequent axillary treatment and thus with less expected morbidity. The effect on recurrence rate is not yet clear. Patients in this registry will be followed prospectively for long-term outcome.

Compliance with guidelines is related to better local recurrence-free survival in ductal carcinoma in situ

The aim was to study the effect of compliance with guidelines on local recurrence (LR)-free survival in patients treated for ductal carcinoma in situ (DCIS). From January 1992 to December 2003, 251 consecutive patients had been treated for DCIS in two hospitals in the North Netherlands. Every case in this two-hospital sample was reviewed in retrospect for its clinical and pathological parameters. It was determined whether treatment had been carried out according to clinical guidelines, and outcomes in follow-up were assessed. In addition, all patients treated for DCIS in this region (n=1389) were studied regarding clinical parameters, in order to determine whether the two-hospital sample was representative of the entire region. In the two-hospital sample, 31.4% (n=79) of the patients had not been treated according to the guidelines. Positive margins were associated with LR (hazard ratio (HR)=4.790, 95% confidence interval (CI) 1.696–13.531). Breast-conserving surgery and deviation from the guidelines were independent predictors of LR (HR=7.842, 95% CI 2.126–28.926; HR=2.778, 95% CI 0.982–6.781, respectively). Although the guidelines changed over time, time was not a significant factor in predicting LRs (HR=1.254, 95% CI 0.272–5.776 for time period 1992–1995 and HR=1.976, 95% CI 0.526–7.421 for time period 1996–1999). Clinical guidelines for the treatment of patients with DCIS have been developed and updated from existing literature and best evidence. Compliance with the guidelines was an independent predictor of disease-free survival. These findings support the application of guidelines in the treatment of DCIS.

Abstract S3-05: Higher 10-year overall survival after breast conserving therapy compared to mastectomy in early stage breast cancer: A population-based study with 37,207 patients

Background: Randomised controlled trials have shown that breast conserving therapy (conserving surgery with radiation therapy, BCT) has equal overall survival (OS) rates as mastectomy without radiation therapy (MAST) in early stage breast cancer. However, 10-year disease-free survival (DFS) in a population-based study was not investigated before. The aim of this study was to compare 10-year OS and DFS after BCT with MAST in Dutch women with early stage breast cancer. Methods: Data of all women diagnosed with primary invasive T1-2N0-1M0 stage breast cancer between 1 January 2000 and 31 December 2004, treated with either BCT or MAST, were selected from the Netherlands Cancer Registry. Multivariable Cox proportional hazard analysis was performed to estimate 10-year OS, stratified for T and N stage. Ten-year DFS was determined in a subgroup of patients diagnosed in 2003, of which an active follow-up was conducted registering all recurrent events within 10 years. Multiple imputation was performed to account for missing data. Results: Of in total 37,207 patients, 21,734 patients (58.4%) received BCT and 15,473 patients (41.6%) received MAST. The subcohort of 2003 consisted of 7,552 patients, with similar distributions of treatments and characteristics. In the total cohort, 10-year OS was 76.8% (99% CI: 76.1-77.5%) after BCT and 59.7 (99% CI: 58.7-60.7%) after MAST. After correction for confounding, 10-year OS was better after BCT than after MAST (HRadjusted: 0.79 [99% CI 0.75-0.83]). In the 2003 cohort, 10-year DFS was 83.6% (99% CI: 82.5-84.7%) after BCT and 81.5% (99% CI: 79.6-83.4%) after MAST. After correction for confounding, 10-year DFS was comparable for both treatments (HRadjusted 0.91 [99% CI 0.77-1.07]). All results were similar for all subgroups (Table). In the 2003 cohort, 11.0% of the patients experienced distant metastases (DM) after BCT compared to 14.7% after MAST (p Conclusion: BCT showed substantially improved OS compared to MAST. However, while DFS was similar, patients treated with BCT less often developed RR and DM. Although residual factors might explain part of the difference in recurrences, we hypothesise that radiation therapy might largely be responsible for better OS by eliminating residual tumour cells. Citation Format: van Maaren MC, de Munck L, de Bock GH, Jobsen JJ, van Dalen T, Poortmans P, Linn SC, Strobbe LJA, Siesling S. Higher 10-year overall survival after breast conserving therapy compared to mastectomy in early stage breast cancer: A population-based study with 37,207 patients. [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 S3-05.

Abstract P6-02-05: Digital versus screen-film mammography in population-based breast cancer screening: Performance indicators and tumor characteristics of screen-detected and interval cancers

Purpose: To evaluate whether the introduction of full-field digital mammography (FFDM) in screening has resulted in any changes in performance indicators compared to screen-film mammography (SFM), including tumor characteristics and incidence rates of interval cancers. Materials and Methods Data of the Dutch National Cancer Screening Programme, region North (2004-2010) were linked to the Netherlands Cancer Registry (N=902,868). Screening performance indicators (recall rate, detection rate, positive predictive value, sensitivity and specificity) and tumor characteristics of screen-detected cancers were compared between FFDM and SFM, as were incidence rates and tumor characteristics of interval cancers. Analyses were stratified by initial and subsequent examinations. Differences were compared using chi-square. Results Initial examinations: After initial examinations recall rates were 2.1% for SFM and 3.0% for FFDM (p Subsequent examinations: After subsequent examinations performance indicators were similar. Detection rates for DCIS were 0.74 per 1000 women for SFM versus 0.81 per 1000 women for FFDM (p=0.298). For invasive cancers, detection rates were 4.54 per 1000 women for SFM versus 4.33 per 1000 women for FFDM (p=0.210). The percentages of low grade DCIS were similar for SFM and FFDM (12% vs.9%; p=0.524). Invasive cancers diagnosed with FFDM were more often of high grade (p=0.024) and ductal type (p=0.030). No difference was found in the incidence rates of interval cancers for SFM and FFDM after initial examinations (2.69/1000 vs.2.51/1000; p=0.787). The sensitivity after initial examinations was 66.1% for SFM and 69.1% for FFDM (p=0.657), specificity was 98.5% and 96.9% for SFM and FFDM, respectively (p Conclusions Compared to SFM, FFDM resulted in similar rates of screen-detected and interval cancers, indicating that FFDM performs as well as SFM in a breast cancer screening program, with more invasive cancers of high grade and ductal type found after subsequent screens. FFDM resulted in a higher recall rate and lower PPV. No signs of an increase in low-grade DCIS (which might connote possible overdiagnosis) were seen. Tumor characteristics of interval cancers were similar. Citation Format: De Munck L, De Bock GH, Otter R, Reiding D, Broeders MJM, Willemse PHB, Siesling S. Digital versus screen-film mammography in population-based breast cancer screening: Performance indicators and tumor characteristics of screen-detected and interval cancers. [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 P6-02-05.

Advanced stage breast cancer is less often diagnosed in women who attend breast cancer screening

1 Netherlands Comprehensive Cancer Organisation, Utrecht; 2 University of Groningen, University Medical Center Groningen, Groningen; 3 Erasmus MC, University Medical Center Rotterdam, Rotterdam; 4 Dutch Reference Centre for Screening, Nijmegen; 5 Academic Medical Centre Amsterdam, Amsterdam; 6 MIRA Institute for Biomedical Technology and Technical medicine, University of Twente, Enschede; 7 Radboud University Medical Center, Nijmegen; the Netherlands Netherlands comprehensive cancer organisation

Interval breast cancers have worse tumor characteristics and survival compared to screen-detected breast cancers

Background There is debate to what extend screen-detected cancers (SDC) differ in tumor characteristics and survival from tumors that are detected not trough screening. These can be divide into three groups. Firstly, tumors who manifest clinically in the period between two screens after a negative screening (interval cancers) within 12 months or, secondly, within 12-24 months. Thirdly, we identified tumors in patients with a positive screening, followed by a benign assessment in the hospital, who developed breast cancer 12-24 months after screening (IC-after-positive-screen). The aim of this study was to determine whether interval cancers and IC-after-positive-screen have worse tumor characteristics and survival compared to SDC. Regarding decision-making for more aggressive treatment, these data are essential. Methods All women (50-75) who underwent a screening by the Dutch National Screening Program, region North between 2004-2008 were selected and data were merged with the Netherlands Cancer Registry. SDC (diagnosed <12 months after positive screening), interval cancers diagnosed <12 months after negative screening (IC<12) or 12-24 months after negative screening (IC12-24), and IC-after-positive-screen were identified. Tumor characteristics of each group were compared to SDC using chi2. Differences in survival were analyzed with multivariable Cox regression, corrected for differences in tumor characteristics. Results In total 4,472 patients were included, 3,363 SDC, 501 IC<12m, 861 IC12-24m and 48 IC-after-positive-screen. Of all SDC, 14% were diagnosed as in situ cancers. A lower percentage of in situ cancers was diagnosed in IC<12m and IC12-24m (6% and 4%, respectively; p<0.001). In situ cancers were diagnosed in 15% of IC-after-positive-screen. Compared to SDC, invasive IC<12m and IC12-24m were more often poorly differentiated (p<0.001), larger than 2 cm (p<0.001), and had more often positive lymph nodes (p<0.001) or metastasis (p<0.001; Table 1). Furthermore, invasive IC<12m and IC12-24m were less often of the ductal type (p=0.002) or hormone receptor positive (p<0.001), compared to SDC. IC-after-positive-screen were not statistically significant different from SDC for all these factors. In total 608 (13%) women died. No difference in survival was found for IC<12m (HR=0.86, 95%CI=0.66-1.12) and IC-after-positive-screen (HR=1.40, 95%CI=0.58-3.39) compared to SDC. Women with an IC12-24m had a worse survival than SDC (HR=1.44, 95%CI=1.17-1.77). Conclusions IC<12m and IC12-24m had less favorable characteristics than SDC. IC-after-positive-screen had similar characteristics and have a similar prognosis as SDC. However, as the number of IC-after-positive-screen was small, this should be part of further research. Women with an IC12-24 had worse survival compared to SDC.

Abstract P5-14-05: Improved Survival of Patients with Primary Distant Metastatic Breast Cancer in the Period of 1995 — 2007

Introduction During the last fifteen years, important changes have taken place concerning the sy stemic treatment for patients with metastasized breast cancer. It would be interesting to know whether these improvements have also taken place patients with primary distant metastatic breast cancer. Additionally, several retrospective studies have shown an improvement in overall survival in patients who have received breast surgery. Therefore, we also analyzed the role of surgical resection of the primary breast tumor. Methods According to the database of the Dutch Cancer Registry 7,358 (5.0%) patients were diagnosed with primary distant metastases between 1997 and 2007. To establish whether improvement of prognosis had taken place, patients were divided into three periods of diagnosis, based on the year of diagnosis of their disease; 1995-1999, 2000-2003 and 2004-2007. The follow-up of these patients was completed until January 1, 2009. Results The median survival was 1.42 years for patients diagnosed in the period 1995-1999, 1.56 years in the period 2000-2003 and 2.0 years in the period 2004-2007. Only the difference between the periods 2000-2003 and 2004-2007 was statistically significant (P An improvement of six months is seen in the median survival of patients with primary distant metastatic breast cancer, resulting in a median survival of two years in 2007. Maybe, if surgery was more performed in the most recent time period, the improvement of the median survival was even better. However, it seems reasonable to argue that this improvement is due to new developments in systemic treatment. Figures available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-05.