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Background Breast cancer treatment with radiotherapy can induce late radiation toxicity, characterized by pain, fibrosis, edema, impaired arm mobility, and poor cosmetic outcome. Hyperbaric oxygen therapy (HBOT) has been proposed as treatment for late radiation toxicity; however, high-level evidence of effectiveness is lacking. As HBOT is standard treatment and reimbursed by insurers, performing classic randomized controlled trials is difficult. The “Hyperbaric OxygeN therapy on brEast cancer patients with late radiation toxicity” (HONEY) trial aims to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the trial within cohorts (TwiCs) design. Methods The HONEY trial will be conducted within the Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA). Within UMBRELLA, breast cancer patients referred for radiotherapy to the University Medical Centre Utrecht are eligible for inclusion. Patients consent to collection of clinical data and patient-reported outcomes and provide broad consent for randomization into future intervention studies. Patients who meet the HONEY in- and exclusion criteria (participation ≥ 12 months in UMBRELLA, moderate/severe breast or chest wall pain, completed primary breast cancer treatment except hormonal treatment, no prior treatment with HBOT, no contraindications for HBOT, no clinical signs of metastatic or recurrent disease) will be randomized to HBOT or control group on a 2:1 ratio (n = 120). Patients in the control group will not be informed about participation in the trial. Patients in the intervention arm will undergo 30–40 HBOT treatment sessions in a high pressure chamber (2.4 atmospheres absolute) where they inhale 100% oxygen through a mask. Cohort outcome measures (i.e., physical outcomes, quality of life, fatigue, and cosmetic satisfaction) of the HBOT group will be compared to the control group at 3 months follow-up. Discussion This pragmatic trial within the UMBELLA cohort was designed to evaluate the effectiveness of HBOT on late radiation toxicity in breast cancer patients using the TwiCs design. Use of the TwiCs design is expected to address issues encountered in classic randomized controlled trials, such as contamination (i.e., HBOT in the control group) and disappointment bias, and generate information about acceptability of HBOT. Trial registration ClinicalTrials.gov. NCT04193722. Registered on 10 December 2019.

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.

Purpose: To evaluate patient-reported work ability of breast cancer patients, to compare scores with the Dutch general population, and to identify determinants of reduced work ability in breast cancer patients. Methods: In a prospective cohort study, we identified 939 patients

Purpose To evaluate patient-reported cosmetic satisfaction in women treated with radiation therapy for breast cancer and to determine the association between dissatisfaction and quality of life (QoL) and depression. Methods Within the prospective UMBRELLA breast cancer cohort, all patients ≥ 1 year after breast conserving treatment or mastectomy with immediate reconstruction were selected. Self-reported cosmetic satisfaction was measured on a 5-point Likert scale. QoL, social functioning, and emotional functioning were measured using EORTC QLQ-C30 and BR23 at 1, 2, and 3 years after inclusion. Mixed model analysis was performed to assess the difference in different domains of QoL between patients with good versus poor self-reported cosmetic satisfaction over time after adjustment for potential confounders. Depression scores were collected by means of the HADS-NL questionnaire. Chi-square test or Fisher's exact test was used to assess the difference in proportions of HADS score ≥ 8, indicating increased depression risk, between satisfied and dissatisfied patients. Results 808 patients were selected for analysis. Respectively one, two, and three years after surgery, 8% (63/808), 7% (45/626), and 8% (31/409) of patients were dissatisfied with their cosmetic outcome. Poor patient-reported cosmetic satisfaction was independently associated with impaired QoL, body image, and lower emotional and social functioning. Scores ≥ 8 on the HADS depression subscale were significantly more common in dissatisfied patients. Conclusions Dissatisfaction with cosmetic outcome was low after breast cancer surgery followed by radiation therapy during 3 years follow-up. Knowing the association between dissatisfaction with cosmetic outcome and QoL and depression could help to improve the preoperative counseling of breast cancer patients.

Purpose We assessed the recent trends in the administration of adjuvant chemotherapy thereby evaluating the role of the 70-gene signature (70-GS) testing in decision-making in the systemic treatment of patients with lymph node negative (N0) and lymph node positive (N+) breast cancer. Methods Patients with a national guideline directed indication for 70-GS use treated between 2013 and 2016 were selected from the Netherlands Cancer Registry. Time trends in the administration of adjuvant chemotherapy were evaluated within guideline- and age-delineated subgroups. The influence of the 70-GS on chemotherapy use was assessed with logistic regression. Results During the study period, the overall administration of adjuvant chemotherapy decreased from 49 to 23% and 70-GS use increased from 24 to 51%. The 70-GS was not associated with a decreased likelihood for N0 patients to receive chemotherapy (odds ratio [OR] 1.0; 95% confidence interval [CI] 0.86–1.17), as the proportion of N0 patients who received chemotherapy in the absence of 70-GS use decreased during the study period. In patients with N1a disease, 70-GS testing was associated with a decreased likelihood to receive chemotherapy (OR 0.21; 95% CI 0.15–0.29). In patients

Aims: To determine the variation in radiation therapy boost use in a nationwide study following adjustment of a national guideline in 2011, as well as to address the relationship to patient, tumour and radiation therapy institutional factors.Materials and methods: All invasive breast cancers and non-invasive breast cancers (ductal carcinoma in situ; DCIS) that received external whole-breast radiation between 2011 and 2016 were selected from the Netherlands Cancer Registry. Box plots were used to evaluate variation over time and logistic regression was carried out to address other factors influencing the variation. Funnel plots were constructed, with unadjusted and adjusted data for patient and tumour factors significantly affecting the use of a boost.Results: For breast cancer patients (n = 45,207), the proportion receiving a boost and its range decreased over the years from 37.3-92.7% in 2011 to 28.3-65.4% in 2016. This trend was not observed in DCIS patients (n = 6,844). Young age, large tumours, high grade and the absence of tumour-free resection margins were associated with boost use for both breast cancer and DCIS. For breast cancer, triple-negative tumour subtype and metastatic lymph node involvement were also associated with boost use. Institutional factors did not influence the use of a boost and institutional variation remained substantial after case-mix adjustments.Conclusion: Following adjustment of a nationwide implemented guideline, variation in radiation therapy boost use decreased in patients with breast cancer but not in patients with DCIS. Several tumour and patient characteristics were associated with boost use. Substantial institutional variation could not be explained by differences in patient, tumour or predefined institutional characteristics. (C) 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Background Ipsilateral breast tumour recurrence (IBTR) has an unfavourable prognosis, with a significant subsequent risk of distant recurrence. Repeat sentinel lymph node biopsy (rSLNB) has recently been demonstrated to be technically feasible and useful in tailoring adjuvant treatment plans in patients with IBTR. The prognostic impact of rSLNB in patients with IBTR remains unclear. This study analysed the risk of distant recurrence after IBTR, and evaluated the prognostic impact of rSLNB and other patient and tumour characteristics on distant recurrence-free survival. Methods Data were obtained from the SNARB (Sentinel Node and Recurrent Breast Cancer) study. Cox proportional hazards analyses were performed to assess the prognostic effect of tumour, patient and treatment factors on distant recurrence-free survival. Results Of the 515 included patients, 230 (44·7 per cent) had a tumour-negative rSLNB and 46 (8·9 per cent) a tumour-positive rSLNB. In 239 patients (46·4 per cent) the rSLNB procedure was unsuccessful. After a median follow-up of 5·1 years, 115 patients (22·3 per cent) had developed a recurrence. The overall 5-year distant recurrence-free survival rate was 84·2 (95 per cent c.i. 80·7 to 87·7) per cent. An interval of less than 2 years between primary breast cancer treatment and ipsilateral recurrence (P = 0·018), triple-negative IBTR (P = 0·045) and absence of adjuvant chemotherapy after IBTR (P = 0·010) were independently associated with poor distant recurrence-free survival. The association between the outcome of rSLNB and distant recurrence-free survival was not statistically significant (P = 0·682). Conclusion The outcome of rSLNB is not an important prognostic factor for distant recurrence, and its value as a staging tool in patients with IBTR seems disputable.

Purpose: Increased insight in tumor biology has revealed that not all young women are at high risk of disease recurrence. Therefore, in some patients extent of treatment could probably be safely scaled down. We aimed to evaluate the risk of breast cancer (BC) relapse according to the 70-gene signature (70-GS) result in relation to young age, in early-stage BC patients enrolled in the MINDACT trial. Patients and Methods: The analyzed population consisted of enrolled BC patients in the MINDACT trial with available clinical (C), as per a modified version of Adjuvant!Online, and genomic (G), according to the 70-GS, risk assessments and known age (n=6693). Patients were categorized in three age groups; 55 years (post-menopausal). Clinicopathological and treatment characteristics as well as gene expression were compared for the different age groups further split by corrected risk groups (C-low/G-low, C-low/G-high, C-high/G-low, C-high/G-high). Subsequently, the 5-year distant metastasis-free survival according to risk category was calculated. Results: The study included 1100 patients 55 years of age (50%). Median age of the young group was 41 (25.8-45.0) years. The young age group had a higher frequency of lymph node involvement (25% vs. 22% and 19%), poorly differentiated tumors (42% vs. 26% and 27%), ER-negative tumors (20% vs. 11% and 11%) and triple negative molecular IHC subtype (16% vs. 9% ad 8%). Median tumor size was the same across the 3 age groups (17mm). Of the 1100 young patients, 61% were C-high while the 70-GS assessed 48% as G-high. Overall, 31% were CL/GL (vs. 43% in other age groups), 9% CL/GH, 21% CH/GL and 40% CH/GH (vs. 24% and 25%). In the discordant risk groups, chemotherapy (CT) allocation when randomized to no chemo occurred in 5% of young women as compared to 3% and 1% in the older age groups. Reason for non-compliance was 50/50 between patient refusal and PI decision. Overall, the 5-year DMFS was 94.1% (95% CI 92.4-95.4) in 55. For the young patients, 5-year DMFS was 98.3% for the CL/GL (96.0-99.3), 97.4% in CL/GH (90.0-99.4), 95.5% in CH/GL (91.6-97.7) and 89.2% in CH/GH (85.6-92.0). In the older two age groups (45-55 and >55), the 5-year DMFS rates were 97.8% (96.5.98.6) and 97.2% (96.2-98.0) for CL/GL, 93.9% (88.8-96.7) and 94.5% (91.0-96.7) for CL/GH, 94.5% (92.0-96.3) and 95.4% (93.5-96.8) for CH/GL and 92.0% (89.2-94.1) and 90.4% (88.0-92.4) for CH/GH, respectively. With 9 events in the Conclusion: The use of the 70-GS reduces the proportion of patients characterized as high risk as compared to traditional clinical risk assessment (48% vs. 61%). Outcome was comparable for the 3 age categories with a very good 5-year DMFS of 95-98% in all GL groups. Performing the 70-GS provides clinically relevant information concerning the prognosis for young early-stage BC patients categorized as CH. These results add important new data to the limited available evidence on genomic expression in young BC patients. Citation Format: Aalders K, Genbrugge E, Poncet C, Kuijer A, Pistilli B, Piccart M, Tryfonidis K, van Dalen T, Cardoso F, van 't Veer L, Rutgers E. Young age and the risk of disease recurrence as assessed by the 70-gene signature – an analysis from the EORTC 10041/BIG 03-04 MINDACT trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-08.

Purpose In Dutch guidelines gene expression profiles (GEP) are indicated in estrogen receptor positive early breast cancer patients in whom benefit of chemotherapy (CT) is controversial based on traditional prognostic factors alone. Aim of the current study is to assess the use and impact of GEP on administration of adjuvant CT in breast cancer patients who have according to national guidelines a clear indication to either use or withhold adjuvant chemotherapy (clinical high or low risk). Methods Clinical low- and high risk patients, according to Dutch breast cancer guidelines, diagnosed between 2011-2014 were selected from the Netherlands Cancer Registry (NCR). Influence of GEP use and GEP test result on CT administration was assessed with logistic regression. Results Overall, 26,425 patients were identified; 4.8% of patients with clinical low- risk (444/ 9,354), 7.5% of the patients with a clinical high-risk (1,281/ 17,071) received a GEP. GEP use was associated with a significantly increased odds of CT administration in clinical low-risk patients (OR=2.12 95%CI: 1.44-3.11). In clinical high-risk patients GEP use was associated with a decreased frequency of CT administration (OR=0.55, 95%CI: 0.48-0.63). Adherence to the GEP result was higher in clinical high-risk patients with a discordant GEP result as compared to clinical low-risk patients with a discordant GEP result: 71.7% vs. 52.2%, respectively. Conclusion GEP is frequently used outside the indicated area and significantly influenced the administration of adjuvant CT, although adherence to the test-result was limited. Citation Format: Schreuder K, Kuijer A, Rutgers EJTh, Smorenburg CH, Van Dalen T, Siesling S. Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-09.

Item does not contain fulltext BACKGROUND: The effect of extended adjuvant aromatase inhibition in hormone receptor-positive breast cancer after sequential endocrine therapy of tamoxifen followed by an aromatase inhibitor for a 5-year treatment period still needs clarification. To address this issue, we began the DATA study to assess different durations of anastrozole therapy after tamoxifen. METHODS: DATA was a prospective, randomised, open-label, multicentre, phase 3 study done in 79 hospitals in the Netherlands. We randomly assigned postmenopausal women with hormone receptor-positive early breast cancer with no signs of disease recurrence after 2-3 years of adjuvant tamoxifen to either 3 or 6 years of anastrozole treatment (1 mg orally once a day) in a 1:1 ratio. We used TENALEA (Trans European Network for Clinical Trials Services) for the randomisation procedure. Stratification factors were nodal status, hormone receptor status, HER2 status, and tamoxifen treatment duration. The primary study endpoint of this analysis was disease-free survival starting beyond 3 years after randomisation (adapted disease-free survival). Here we report the final analysis from the DATA trial, which is registered with ClinicalTrials.gov, number NCT00301457. FINDINGS: Between June 28, 2006, and Aug 10, 2009, we screened 1912 patients of whom 955 were assigned to the 3-year group and 957 to the 6-year anastrozole treatment group. 1860 patients were eligible (931 in the 6-year group and 929 in the 3-year group) and 1660 were disease free 3 years after randomisation. The 5-year adapted disease-free survival was 83.1% (95% CI 80.0-86.3) in the 6-year group and 79.4% (76.1-82.8) in the 3-year group (hazard ratio [HR] 0.79 [95% CI 0.62-1.02]; p=0.066). Patients in the 6-year treatment group had more adverse events than those in the 3-year treatment group, including all-grade arthralgia or myalgia (478 [58%] of 827 in the 6-year treatment group vs 438 [53%] of 833 in the 3-year treatment group) and osteopenia or osteoporosis (173 [21%] vs 137 [16%]). INTERPRETATION: We cannot recommend the use of extended adjuvant aromatase inhibition after 5 years of sequential endocrine therapy in all postmenopausal women with hormone receptor-positive breast cancer. FUNDING: AstraZeneca.

PURPOSE: gene-expression profiles, such as the 70-gene signature (70-GS), are increasingly used as adjunct to conventional clinicopathological prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in estrogen-receptor (ER) positive (+) early stage breast cancer patients without overt lymph node metastases. We aimed to assess the impact of the 70-GS on CT decisions in ER+ early stage breast cancer patients. PATIENTS AND METHODS: In this prospective observational multicenter study physicians were asked for their opinion whether to administer or omit adjuvant CT before deployment and after obtaining the test result of the 70-GS in this guideline delineated group of patients. RESULTS: Between January 1 2013 And December 31 2015 660 patients, treated in 31 hospitals, were enrolled. Based on the clinicopathological postoperative findings physicians would administer CT in 41%, withhold CT in 16% of patients and refrained from formulating an advice in the remaining 43% of patients letting their recommendation depend on the result of the 70-GS. Estimated 5-year survival benefit of CT administration was 0.8%, 0.6% and 0.7% respectively (p 0,585). The 70-GS result hardly varied in relation to the initial advice of the physician: 56% and 59% had a low-risk profile in patients in whom CT was recommended or discommended respectively (r =0.021, Table 1). In 51% of patients in whom a pre-test recommendation was formulated incorporation of the 70-GS test result changed the initial advice. Adherence to the test result was high for the three groups (range 94-97%). Table 1. Concordance between pre-test CT recommendation of the oncologist and the 70-gene signature (GS) test result. 70-GS test resultPre-test CT recommendationno. patientsLow RiskHigh RiskNo CT10763 (59%)44 (41%)CT270152 (56%)118 (44%)Depends on 70-GS result283174 (61%)109 (39%)Note. Agreement between pre-test oncologist CT recommendation and the 70-GS test result: Pearsons r = -0,031 95%CI (-0,11 – 0,045). Table 2. CT recommendation before vs. after obtaining the 70-GS test result and the actual administration of CT. Post-test CT recommendationAdherence to test result*Actual administered CTAdherence to test result*Pre-test CT recommendationno. patientsNo CTCT%No CTCT%No CT10769 (65%)38 (35%)94%73 (68%)34 (32%)91%CT207156 (58%)114 (42%)97%162 (60%)108 (40%)90%Depends on 70-GS result283173 (61%)110 (39%)95%185 (65%)98 (35%)91%*Percentage of patients in whom the post-test recommendation/actual administered CT was in line with the 70-GS test result (i.e. no CT in case of a low-risk profile and CT in case of a high-risk profile. Note. Change in CT recommendation in patients with a CT or no CT pre-test recommendation McNemar's chi-square test p < 0.001 and p < 0.001 for actual administered CT CONCLUSION: guideline-directed use of the 70-GS in Dutch ER+ early breast cancer patients influenced CT treatment decision in the majority of patients. The physician's tentative CT advice was not associated with the 70-GS test-result. Citation Format: Kuijer A, Straver M, Elias S, Smorenburg C, Wesseling J, Linn S, Rutgers E, Siesling S, van Dalen T. Impact of 70-gene signature use on adjuvant chemotherapy decisions in early breast cancer patients: Results of the prospective symphony triple A study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-03.

Background Breast cancer treatment is a multimodality effort to optimize outcome as well as to achieve the optimal cosmetic result. Various treatment strategies can be used for the latter goal: upfront breast conserving surgery (BCS), BCS after neoadjuvant therapy (NAC), and ablative surgery combined with immediate breast reconstruction. The rate of BCS is frequently used as a quality and trend indicator. The aim of the present study was to analyse the combined efforts expressed as the rate of breast contour preserving procedures (BCPP) and compare it to the rate of BCS. Material and methods All invasive M0 female breast cancer patients diagnosed and operated in one of the 89 hospitals in the Netherlands between January 2011 – December 2015 were selected from the national NABON Breast Cancer Audit. BCPP (defined as 'primary BCS', 'BCS after NAC', or 'ablative surgery combined with an immediate reconstruction') was calculated for the years of diagnosis, age groups ( Results A total of 61,309 patients were identified. The rate of upfront BCS remained stable during the study period (52%), while the BCPP rate increased over the years (63% to 71%) due to an equal increase in the proportions of patients receiving NAC with BCS and undergoing ablative surgery with immediate breast reconstruction. While upfront BCS (with and without NAC) rates increased with age (30% in patients aged The rate of BCS varied between hospitals in the Netherlands: 37% to 77%. Although BCPP is more often performed compared to BCS, the variation between hospitals remained (47% to 88%). Table. Percentage of patients treated with Breast Conserving Surgery (BCS), BCS after neo-adjuvant therapy and immediate breast reconstruction with ablative surgery resulting in total percentages of Breast Contour Preserving Procedures (BCPP). BCSBCSAblative surgeryBCPP Neo-adjuvant +IBR + Year of Diagnosis 201153%4%6%63%201253%4%7%64%201352%6%8%67%201452%8%9%69%201552%9%11%71%Age Group Conclusions While the rate of BCS remained stable over recent years, the rate of BCPP has increased significantly. Including immediate reconstruction into the BCPP rate annihilates observed age-dependent differences of the BCS-rates, while institutional differences remained. All in all, combining different treatment strategies into one parameter (BCPP) provides a more appropriate measure of maintaining the breast contour than BCS alone. Citation Format: van Bommel A, Spronk P, Vrancken Peeters M-J, Mureau M, Siesling S, Smorenburg C, van Dalen T. The concept of breast contour preserving surgery as parameter in breast cancer surgery [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-12.

Background In the Dutch breast cancer screening program, women recalled with a BI-RADS 0 score are referred for additional imaging, while those with BI-RADS 4/5 scores are also directed to an outpatient breast clinic. Approximately six out of ten women are recalled without being diagnosed with a malignancy. However, these recalls require additional imaging and doctor visits, which result in patient anxiety and increased health care costs. Conventional types of imaging used for additional imaging are full-field digital mammography and tomosynthesis. Contrast-enhanced spectral mammography has proved to have higher sensitivity and specificity than conventional imaging in women recalled from screening. Therefore, the aim is to study if CESM instead of conventional imaging is a more accurate, patient-friendly, and cost-effective strategy in the work-up of women recalled from breast cancer screening. Methods This prospective, multicenter, randomized controlled trial will be conducted at four centers and will include 528 patients recalled for suspicious breast lesions from the Dutch breast cancer screening program. Participants are randomized in two groups: (1) standard care using conventional breast imaging techniques as initial imaging after recall versus (2) work-up primarily based on CESM. Written informed consent will be collected prior to study inclusion. The primary outcome is the diagnostic accuracy for detection of breast cancer. Secondary outcomes are numbers of additional diagnostic exams, days until final diagnosis, health care costs, and experienced patient anxiety. Discussion Based on previously published retrospective studies, we expect to demonstrate in this prospective multicenter randomized controlled trial, that using CESM as a primary work-up tool in women recalled from breast cancer screening is a more accurate, cost-effective, and patient-friendly strategy. Trial registration Netherlands Trial Register, NL6413/NTR6589. Registered on 6 July, 2017.

Introduction: Historically, young breast cancer patients proved to have a poorer prognosis regarding survival and locoregional recurrence. Over the last two decades, the survival of breast cancer patients has improved substantially, while at the same time locoregional recurrence rates decreased. The diminishing recurrence rates in the overall breast cancer population and acknowledgement of tumor biology and intrinsic subtypes in relation to age, raise the question whether the historically high locoregional recurrence risk in young women has decreased over a time where systemic treatment has evolved, particularly for the aggressive tumor types that occur frequently in young women. The aim of this study was to evaluate contemporary local and regional recurrence rates in very young breast cancer patients in relation to tumor biology in the shape of intrinsic subtypes. Methods: Women Results: A total of 1,000 patients were identified. The overall 5-year LR and RR rates were 3.5% and 3.7% respectively and a decreasing trend for both rates was observed over time. Overall 5-year local, regional and distant recurrence rates over time in breast cancer patients Intrinsic subtype proved to be a prognostic factor for both LR and RR (P=0.0556 and P=0.0141, respectively). Particularly HR-/HER2+ tumors were associated with high LR and RR rates. Patients with lymph node metastases at time of diagnosis had a higher RR-risk in both the total population (P=0.0349) as well as within the different intrinsic subtypes, although only significantly in the triple negative group (P=0.0401). Type of surgery did not influence the rate of LR and RR in this study. Conclusions: Overall, the LR and RR rates in very young breast cancer patients were relatively low and decreased over time. The higher recurrence rates in this population were associated with the presence of more aggressive intrinsic subtypes. We emphasize that tumor biology should guide decision-making towards optimal treatment in this specific population. Although longer follow-up is needed, especially for this very young patient population, the results of this study provide important insight in the locoregional recurrence risks for this historically high-risk population. Citation Format: Aalders KC, Postma EL, Strobbe LJ, van der Heiden-van der Loo M, Sonke GS, Boersma LJ, van Diest PJ, Siesling S, van Dalen T. Contemporary local and regional recurrence rates in very young breast cancer 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 P5-08-01.

Introduction Neo-adjuvant chemotherapy (NAC) is increasingly used in breast cancer to enable less extensive surgery and monitor the response to systemic therapy. Little is known about local recurrence (LR) in patients who received NAC. However, this information is important when deciding on optimal local treatment in these patients, especially since NAC is increasingly being offered to patients with smaller tumors. The aim of this study is to assess the contemporary rates of local breast cancer recurrence in patients that received NAC. Methods All women treated with NAC for primary invasive breast cancer in the years 2003-2008 were selected from the Netherlands Cancer Registry. The first event within five years after NAC was included for analyses. The 5-year local (LR) recurrence rate was calculated using Kaplan Meier estimates and the prognostic value of various clinicopathological and treatment factors was evaluated. Results A total of 2,457 patients were identified of whom 43% had cT1-2, 25% cT3 and 29% cT4 tumors. Two-thirds of the patients had metastatic lymph node involvement and 85% received adjuvant radiotherapy. The overall 5-year risk of LR was 6.7% and decreased from 2003-2008. Table 1. Overall 5-year rate of local breast cancer recurrence in 2,457 breast cancer patients that received neo-adjuvant chemotherapy in the period 2003-2008. Local recurrencea NRate2003N=412309.6%2004N=429288.0%2005N=549398.1%2006N=604234.7%2007N=406164.7%2008N=489245.5%TotalN=2,4571606.7%aLocal recurrence defined as ipsilateral in-breast recurrence or new primary Rates represent Kaplan Meier estimates The LR-rate was lower in hormone receptor positive (HR+) than HR-negative (HR-) tumors (3.3% vs. 12.9%) and increased with larger residual tumor size (from 1.2% in ypT0 to 13.0% in ypT3 and 16.1% in ypT4 tumors). The LR-rate also increased with the ypN-stage (4.1% in ypN0, 5.7% in ypN1 and 11.3% in ypN>1 patients) and was lower following breast-conserving surgery (BCS) than after mastectomy (4.8% vs. 7.2%). Currently, we are working on the multivariate analyses, which will be available at the San Antonio Breast Cancer Symposium. Conclusions The rate of LR in patients treated with NAC has decreased over time. This will most likely be caused by enhanced imaging and radiotherapy techniques, as well as by increased insight in tumor biology resulting in improvements in both the development and application of systemic treatment modalities. Multivariate analyses will have to provide further insight into the risk of developing LR in patients treated with NAC, as well as into the prognostic value of different clinicopathological factors. Citation Format: Aalders KC, Sonke GS, van der Heiden-van der Loo M, Boersma LJ, van Diest PJ, Siesling S, van Dalen T. Contemporary risk of local breast cancer recurrence after neo-adjuvant chemotherapy: Results of a population-based cohort study. [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 P5-08-36.

Over recent years, adjuvant systemic treatment guidelines (AST) for early-stage breast cancer have changed considerably. We aimed to assess the impact of these guideline changes on the administration of AST in early-stage breast cancer patients and to what extent these guidelines are adhered to at a nation-wide level. We used Netherlands Cancer Registry data to describe trends in AST prescription, adherence to AST guidelines, and to identify clinicopathological determinants of nonadherence. Between 1990 and 2012, 231,648 Dutch patients were diagnosed with early breast cancer, of whom 124,472 received AST. Adjuvant endocrine treatment (ET) use increased from 23 % of patients (1990) to 56 % (2012), and chemotherapy from 11 to 44 %. In 2009–2012, 8 % of patients received ET and 3 % received chemotherapy without guideline indication. Conversely, 10–29 % of patients did not receive ET and chemotherapy, respectively, despite a guideline indication. Unfavorable clinicopathological characteristics generally decreased the chance of undertreatment and increased the chance for overtreatment. Remarkable was the increased chance of ET undertreatment in younger women (RR

PURPOSE: A decade ago intrinsic biological breast cancer subtypes have been identified which have proven to be of clinical importance in terms of outcome and response to systemic treatment. The aim of the current study is to assess concordance between breast cancer subtypes determined by local immunohistochemistry (IHC) assessment of estrogen receptor (ER), progesterone receptor (PR) and Her2-receptor status and microarray based molecular subtyping in a subset of ER+ early stage breast cancer patients. PATIENTS AND METHODS: In this prospective observational multicenter study information on local pathology assessment and BluePrint/TargetPrint results were obtained in ER+ Dutch early stage breast cancer patients in whom a 70-gene profile (MammaPrint) was used as they were enrolled in clinical trial based on the existence of controversy regarding the additional value of adjuvant CT. Local IHC assessment of ER, PR and Her2 status were compared with microarray based assessment (TargetPrint/BluePrint) of these characteristics. Reclassification of ER and PR overexpression was assessed by a McNemars test and by Spearman correlation. Furthermore, concordance between the clinical subtypes based on local pathology (Luminal-type: ER+/PR+/Her2-; Her2-type: Her2+ disease) and molecular subtyping was assessed. RESULTS: Between January 2013 And December 2015 660 patients, treated in 31 hospitals, were enrolled. In 564 (85%) BluePrint and/or TargetPrint was performed in addition to the 70-GS. The majority of patients had ER+/Her2- disease and TargetPrint reclassified 1% (n = 7) of patients as ER-negative (r = 0,250, p Table 1. Concordance between immunohistochemistry and TargetPrint. TargetPrint result (ER, PR and Her2 resp.) ImmunohistochemistryPositiveNegativeOverall discordance (%)p-value*Estrogenreceptor status Positive557 (99%)6 (1%) Negativen.a.n.a.1%n.a.Progesterone receptor status Positive474 (96%)18 (4%) Negative22 (31%)49 (69%)7%0,636Her2 receptor status Positive3 (30%)7 (70%) Negative4 (3%)546 (97%)2%0,549Equivocal0 (0%)3 (1%) * P-value represents results of the McNemar test.). Based on IHC 545 (98%) patients were regarded as luminal-type and the remaining 2% as Her2-type. BluePrint reclassified 2% of the clinical luminal-type patients: 4 (1%) patients were reclassified as basal-type and 3 (0%) patients as Her2-type. Of the clinical Her2-type patients 80% (n=8) was reclassified by BluePrint as molecular luminal-type. Table 2. Concordance between clinical subtyping and molecular subtyping according to BluePrint. BluePrint resultClinical SubtypeNo. ptsLuminalBasalHer2Luminal545539 (99%)4 (1%)3 (0%)Her2108 (80%)02 (20%)Note. Overall discordance 3%. Conclusion: In the current study we observe a high concordance between microarray-based assessment of ER, PR and Her2 and local pathology in Dutch ER+ early stage breast cancer patients. In the small subset of ER+ patients who are considered candidates for 70 GS use and who have HER2+ tumors by IHC molecular typing of HER2 status is of additional value. Citation Format: Kuijer A, Straver M, Elias S, Smorenburg C, Wesseling J, Linn S, Rutgers E, Siesling S, van Dalen T. Concordance of local immunohistochemistry with TargetPrint microarray based assessment of ER, PR and Her2 and BluePrint molecular subtyping in the Symphony Triple A study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-03-04.

Purpose: All Dutch hospitals are obliged to report their 5-year ipsilateral breast tumor recurrence (IBTR) rate after breast cancer surgery. Experts decided that these rates should not exceed 5 %. This study determined the value of IBTR as an indicator to compare quality of care between hospitals. Methods: All patients with breast cancer (pT1–3, any N, M0) who underwent surgery in 1 of 92 Dutch hospitals from 2003 to 2006 were identified in the Netherlands Cancer Registry. Data of recurrence was retrieved from hospital records. Five-year IBTR rates for breast-conserving surgery (BCS) and mastectomy were calculated by using the Kaplan–Meier method. Hospital variation was presented in funnel plots. Multivariate analysis was used to assess hospital characteristics associated with IBTR rates. Results: A total of 40,892 breast cancer patients were included. The overall 5-year IBTR rate was 2.85 % (95 % confidence interval 2.68–3.03) and was significantly lower for BCS than for mastectomy (2.38 vs. 3.45 %, p < 0.001). IBTR rates decreased over time in both groups. Rates varied between 0.77 and 5.70 % between hospitals. When random variation is taken into account, only extremely high IBTR rates can be detected as deviant from the target value of 5 %. Adjusting for tumor and patient characteristics, analyses showed that a higher volume of mastectomies is associated with lower IBTR rates. Conclusions: Our population-based findings show that IBTR rates in the Netherlands are low and have improved over time. The 5-year IBTR rate as an indicator for quality of care of individual hospitals is of limited value.

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 Table. Adjusted hazard ratios of breast-conserving surgery with radiation therapy vs. mastectomy on 10-year overall and disease-free survival in T1-2N0-1 staged breast cancer patients n10-year OS [99% CI]10-year DFS [99% CI]Overall cohort MAST15,47311BCT21,7340.79 [0.75-0.83]0.91 [0.79-1.07]Subgroups T1N0 MAST6,09211BCT18,8600.80 [0.74-0.87]0.81 [0.62-1.08]T1N1 MAST2,18511BCT3,7410.80 [0.69-0.92]1.02 [0.64-1.63]T2N0 MAST4,17411BCT3,1650.79 [0.70-0.88]0.99 [0.72-1.35]T2N1 MAST3,02211BCT2,0600.77 [0.67-0.88]0.82 [0.58-1.15]All hazard ratios are adjusted for all relevant confounders. Abbreviations: MAST = mastectomy; BCT = breast conserving surgery with post-operative radiation therapy; OS = overall survival; DFS = disease-free survival 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.

Background We aimed to assess whether socioeconomic status (SES) and ethnicity affect adjuvant systemic therapy (AST) guideline adherence in early breast cancer patients in a health care setting with assumed equal access to care. Methods Data from all female patients surgically treated for primary unifocal early breast cancer between January 2005 and December 2014 were retrieved from the Netherlands Cancer Registry. We assessed the association between SES, ethnicity and non-adherence to adjuvant chemotherapy (CT) or endocrine therapy (ET) guideline indications with Poisson regression models, adjusting for clinicopathological variables. Results A total of 104 201 patients were included in the current analysis. Of patients without an indication, 4% and 13% received adjuvant CT or ET (overtreatment), whereas 39% and 14% of patients with an indication did not receive CT or ET (undertreatment). Medium and low SES patients were 1.01 (95% CI 1.00–1.01) and 1.01 (95% CI 1.00–1.01) times more likely to be undertreated and 0.85 (95% CI 0.76–0.94) and 0.67 (95% CI 0.60–0.75) times more likely to be overtreated with CT compared with high SES patients [resulting in an overall relative risk of CT use of 0.94 (95% CI 0.92–0.96) and 0.85 (95% CI 0.83–0.87), respectively]. No association between SES and ET guideline adherence or ethnicity and CT/ET guideline adherence was observed. Conclusion In the Netherlands, minimal SES disparities in CT guideline adherence were observed: low SES patients are less likely be overtreated and marginally more likely to be undertreated with CT resulting in an overall decreased risk of receiving CT. No ethnical disparities in AST guideline adherence were observed.

Background A shift towards less burdening and more patient friendly treatments for breast cancer is currently ongoing. In low-risk patients with early-stage disease, accelerated partial breast irradiation (APBI) is an alternative for whole breast irradiation following breast-conserving surgery. MRI-guided single dose ablative APBI has the potential to offer a minimally burdening, non-invasive treatment that could replace current breast-conserving therapy. Methods The ABLATIVE study is a prospective, single arm, multicenter study evaluating preoperative, single dose, ablative radiation treatment in patients with early-stage breast cancer. Patients with core biopsy proven non-lobular invasive breast cancer, (estrogen receptor positive, Her2 negative, maximum tumor size 3.0 cm on diagnostic MRI) and a negative sentinel node biopsy are eligible. Radiotherapy (RT) planning will be performed using a contrast enhanced (CE) planning CT-scan, co-registered with a CE-MRI, both in supine RT position. A total of twenty-five consecutive patients will be treated with a single ablative RT dose of 20 Gy to the tumor and 15 Gy to the tumorbed. Follow-up MRIs are scheduled within 1 week, 2, 4 and 6 months after single-dose RT. Breast-conserving surgery is scheduled at six months following RT. Primary study endpoint is pathological complete response. Secondary study endpoints are the radiological response and toxicity. Furthermore, patients will fill out questionnaires on quality of life and functional status. Cosmetic outcome will be evaluated by the treating radiation oncologist, patient and ‘Breast Cancer Conservation Treatment cosmetic results’ software. Recurrence and survival rates will be assessed. The patients will be followed up to 10 years after diagnosis. If patients give additional informed consent, a biopsy and a part of the irradiated specimen will be stored at the local Biobank and used for future research on radiotherapy response associated genotyping. Discussion The ABLATIVE study evaluates MRI-guided single dose ablative RT in patients with early-stage breast cancer, aiming at a less burdening and non-invasive alternative for current breast-conserving treatment. Trial registration ClinicalTrials.gov registration number NCT02316561. The trial was registrated prospectively on October 10th 2014. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3144-5) contains supplementary material, which is available to authorized users.

Contains fulltext : 174953.pdf (Publisher’s version ) (Open Access) BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Background Obtaining tumor free resection margins is essential in patients undergoing breast conserving surgery. Several risk factors associated with positive margins are described in literature. We developed a prediction model to predict positive resection margins in patients undergoing breast conserving surgery of non-palpable lesions. Methods A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery at five different hospitals in the Netherlands. A prediction model for positive resection margins was built using multivariate regression analysis and internally validated by bootstrapping. Results Positive resection margins were present in 69/576 (12%) patients. Factors associated with positive margins included microcalcifications on mammography (OR 1.8, 1.0-3.2), tumor not visible on ultrasound (OR 2.6, 1.2-5.6), presence of DCIS (OR 2.3, 1.3-4.0), multifocality (OR 3.5, 1.0-12.1), caudal location in the breast (OR 1.9, 1.1-3.5), and invasive tumor size (OR 1.83, 1.6-2.7). Together, these factors were able to moderately discriminate between patients with positive versus negative margins (area under the ROC 0.71, 95% CI 0.648 – 0.780). After internal validation the discrimination was slightly lower with an AUC of 0.694. Prevalence of positive margins was 5.2% in the highest risk quintile versus 26.3% in the lowest quintile. Conclusion A model predicting positive resection margins after breast conserving surgery in non-palpable breast cancer was built. This model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning (eg. preoperative MRI) and informing of patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-03.

One-stop surgery offers patients diagnostic work-up and subsequent surgical treatment on the same day. In the present study, patient satisfaction and efficiency from an institutional perspective were evaluated in patients who were referred for one-stop endoscopic inguinal hernia repair. In a high-volume inguinal hernia clinic, all consecutive patients referred for one-stop surgical treatment, were registered prospectively. An instructed secretary screened patients for eligibility for the one-stop option when the appointment was made. Totally extraperitoneal hernia repair under general anaesthesia was the preferred operative technique. Patient’s satisfaction, successful day surgery and institutional efficiency were evaluated. Between January 2010 and January 2012 a total of 349 patients (17 % of all patients in the hernia clinic) were referred for one-stop hernia repair. Mean age was 47.5 years and 96.3 % were males. Three hundred thirty-six patients underwent hernia surgery on the same day (96.3 %). In thirteen patients (3.7 %) no operative repair was done on the day of presentation due to an incorrect diagnosis (n = 7), a watchful waiting policy for asymptomatic hernia (n = 3), rescheduling due to a large scrotal hernia, and there were two “no shows”. Following hernia repair 97 % of the patients were discharged on the same day, while ten patients required hospitalization. Based on the questionnaires the main satisfaction score among patients was 9.0 (8.89–9.17 95 % CI) on a scale ranging from 0 to 10. One-stop hernia surgery is feasible and satisfactory from an institutional as well as from a patient’s perspective.

Background Desmoid-type fibromatosis is a locally aggressive soft tissue tumour with a biological behaviour that varies between relatively indolent and progressive growth. Although there is a trend towards conservative treatment, surgery remains the standard treatment for extra-abdominal desmoid tumours. Methods Databases of three hospitals were searched to identify patients who had been treated for desmoid-type fibromatosis between November 1989 and May 2011. The risk of local recurrence was evaluated and predictive factors were assessed in patients who underwent surgical resection as initial treatment for a primary tumour. Results A total of 132 patients had surgical treatment for a primary tumour. A complete resection (R0) was achieved in 87 patients (65·9 per cent). In addition to surgery, 54 patients received radiotherapy. During a median follow-up of 38 months, 18 local recurrences were detected. The estimated 5-year cumulative risk of local recurrence was 17·6 per cent. Univariable Cox regression analysis demonstrated that the risk of local recurrence increased for extremity lesions compared with desmoids on the trunk (odds ratio 6·69, 95 per cent confidence interval 1·42 to 31·54). No significant influence of age, resection margins or adjuvant radiotherapy on the risk for local recurrence was observed. Conclusion Following surgical treatment of a primary extra-abdominal desmoid tumour, the 5-year risk of local recurrence is modest and not influenced by microscopically clear resection margins or adjuvant radiotherapy.

Contains fulltext : 170974.pdf (Publisher’s version ) (Open Access) Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non-Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total of 156 Turkish/Moroccan patients were identified, and 321 patients were assigned to the comparative group. About one third (35%) of the Turkish/Moroccan patients fulfilled criteria for breast cancer genetic counseling, compared to 21% of the comparative group (P = 0.001); this was largely due to a relatively young age at diagnosis in the migrant group (26%

Background: The effectiveness of intraoperative ultrasound (IOUS) for preoperative localization of non-palpable breast cancers within the operation theatre has not been studied extensively. In this prospective cohort study, we compared margin status, re-excision rate and excised volume of IOUS to guidewire localization (GWL). Methods: A total of 258 consecutive patients with non-palpable invasive breast cancer underwent breast conserving surgery between 1999–2010. GWL was performed in 138 (54%) and IOUS in 120 (46%) patients. Tumour dimensions, resection volume, margin status and re-excision rates were compared by means of multivariate regression analysis. Calculated resection ratios, i.e. indicating the amount of excess tissue resection, were calculated by dividing the total resection volume by the optimal resection volume (the tumor diameter plus a 1.0 cm margin) and compared between the groups. Results: The groups were similar in terms of age, histological subtype and presence of DCIS. Lesions in the IOUS group were larger (1.24 vs. 0.98 cm), while lesions in the GWL group consisted more often of microcalcifications only (19% vs. 3%). Tumour free resection margins were obtained in more than 93% of patients (93.5% with GWL vs. 93.3% with IOUS, P = .958) and re-excision was performed in 11.0% of patients undergoing GWL and 12.5% of patients undergoing IOUS (P = .684). In both groups, resection volumes were similar, but IOUS led to more optimal tissue resection (calculated resection ratio 4.33 vs 3.30, P = .018). After adjustment for tumor diameter, radiological findings and presence of DCIS, the difference in calculated resection volumes was no longer significant. Conclusion: For localization of non-palpable breast cancer, IOUS is a reliable alternative to GWL, as it achieves similar results in terms of complete tumour removal, re-excision rate and excised volume. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-08.

Introduction: Female breast cancer patients carrying a BRCA1/2 mutation have an increased risk of second primary breast and ovarian tumors. Rapid genetic counseling and testing (RGCT) may aid in making informed decisions about therapeutic and preventive surgery and adjuvant treatment. Little is known about the effects of RGCT on treatment decisions and psychosocial well-being. We have performed a randomized controlled trial to investigate these issues. Methods: Newly diagnosed breast cancer patients from 12 Dutch hospitals with at least a 10% risk of carrying a BRCA1/2 mutation were randomized to an intervention group (RGCT) or a usual care control group (ratio 2:1). Study outcomes included uptake of RGCT, choice of type of surgery, cancer risk perception, cancer-specific distress, quality of life and decisional satisfaction. Assessments took place at study entry, and at 6 and 12 months follow-up. Results: Between 2008 and 2010, 271 patients were recruited, of whom 3 subsequently withdrew. The remaining 268 patients were randomized to the intervention (n = 181) or control (n = 87) group. Complete questionnaire data were available for 250 (93%) and 243 (91%) patients at 6 and 12 months follow-up, respectively. Of the 181 women in the intervention group, 180 (98%) underwent genetic counseling after a median of 4 days. One-hundred thirteen (63%) of them opted for accelerated DNA test procedures, of whom 72 underwent rapid testing (results available in Conclusion: The uptake of rapid genetic counseling among high-risk breast cancer patients was high, and the majority of patients underwent accelerated DNA-testing procedures. However, RGCT did not have a significant effect on choice of type of primary surgery. In part, this may be explained by the fact that surgeons and patients often did not wait for DNA test results before primary surgery. Conclusions regarding the psychosocial impact of RGCT will be presented at the time of the conference. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-11-01.

In patients with inguinal hernias, sexual activity may be impaired due to hernia-related pain. Surgical repair may improve these complaints but can also lead to similar symptoms as a long-term complication of the operation. Endoscopic hernia repair is associated with less postoperative pain and earlier return to normal activities, but its effect on pain-related sexual function is unknown. In this study, the incidence and effect of pain related to sexual activity are evaluated before and after endoscopic totally extraperitoneal (TEP) hernia repair. A hospital-based questionnaire study of pain-related sexual dysfunction was conducted in November 2009 in 500 male patients ≥18 years, who underwent TEP repair of a primary hernia between March 2006 and December 2008. The response rate was 77.2%. Pain of any severity during sexual activity was reported by 124 patients (32.1%) preoperatively and 35 patients (9.1%) postoperatively. Only 2.3% of the 262 patients with no history of preoperative pain experienced moderate to severe (VAS 4–10) pain postoperatively. Pain impaired sexual function in 63 patients (16.3%) preoperatively and in 18 patients (4.7%) postoperatively. The majority of patients who reported pain during sexual activity preoperatively (n = 102, 82.3%) had no pain postoperatively. The frequency of moderate to severe painful sexual activity decreased from 21.2% (preoperatively) to 3.4% after TEP repair (P

Objective: In patients with extremity soft tissue sarcomas (STSs) a correct histopathological diagnosis is considered important before surgical treatment. We evaluated the preoperative use and sensitivity of the various pathology techniques. Methods: In a population-based study in patients operated for a newly diagnosed extremity STS between January 2000 and December 2003 the preoperative pathology work-up was evaluated. Data were retrieved from a national pathology database (PALGA). The sensitivity of the three techniques was assessed considering an examination affirmative when the conclusion of the pathology report stated the presence of mesenchymal malignancy. Results: The pathology reports of 573 patients were identified in the database. In 177 patients (31%) no pathology examination was done before resection of the tumour. In the remaining 396 patients the pathology procedure of first choice had been an incisional biopsy (113) in 195 patients (49%), a core-needle biopsy (CNB) in 90 patients (23%) and a fine needle aspiration (FNA) in 111 patients (28%). All affirmative diagnosis was established in 95% of the patients following an 113, in 78% after a CNB and in 38% following FNA. After an initial CNB an additional 113 was performed in 18 of the 90 patients improving the yield to 89%. After an initial FNA a subsequent histological biopsy was done in 53 of the 111 patients, increasing the sensitivity to 71%. Conclusions: In this population-based Study in patients treated for extremity STS, the proportion of patients operated without preoperative pathology evaluation was high. In the remaining patients an incisional biopsy was still the most commonly performed technique with the highest yield. (C) 2009 Elsevier Ltd. All rights reserved.

Background The prognostic meaning and thus indication for adjuvant therapy of lymphogenic micrometastases in breast cancer patients is still under debate. Patients and methods From 1999 to 2007, 703 patients with (c)T(1-2)N(0) breast cancer underwent surgery including sentinel lymph node biopsy. Examination of sentinel lymph nodes consisted of hematoxylin and eosin and immunohistochemistry staining following serial sectioning of the sentinel node. Patients were divided into four groups: (p)N(0) (n=423), (p)N(1micro) (n=81), (p)N(1a) (n=130) and (p)N(>or=1b) (n=69). Median follow-up was 40 months. Results At the end of follow-up, 53 patients had died and 64 had recurrent disease. Compared with (p)N(0) and following adjustment for possible confounders, including adjuvant systemic treatment, overall survival was not significantly different for (p)N(1micro) while significantly worse for (p)N(1a) and (p)N(>or=1b) {hazard ratio (HR) [95% confidence interval (CI)]: 0.59 [0.14-2.58], 4.31 [1.85-10.01], 10.66 [4.04-28.14], respectively}. Likewise, disease-free survival was not significantly different for (p)N(1micro) and worse for (p)N(1a) and (p)N(>or=1b) (HR [95% CI]: 1.43 [0.67-3.02], 2.79 [1.37-5.66], 7.13 [3.27-15.54], respectively). Distant metastases were more commonly observed in the (p)N(1micro) than in the (p)N(0) group, but still not as common as in the (p)N(1a) or (p)N(>or=1b) group (HR [95% CI]: 4.85 [1.79-13.18], 10.34 [3.82-28.00], 23.25 [7.88-68.56], respectively). Conclusion Although the risk of distant metastases was higher in patients in the (p)N(1micro) than in the (p)N(0) group, no statistically significant differences were observed in overall or disease-free survival between (p)N(0) and (p)N(1micro). Micrometastatic lymph node involvement in itself should not be an indication for adjuvant chemotherapy in breast cancer patients.

Background: Inguinal pain after groin hernia repair is a challenging issue. About 50 % of postherniorrhaphy pain allegedly is neuropathic, treatment of which is cumbersome given the limited efficacy of current therapeutic modalities. Possibly a clear protocol assessing the type of pain and treating it accordingly could improve its treatment. Methods: A prospective study was done to evaluate an algorithm in patients with chronic postherniorrhaphy groin pain, aiming to select those with neuropathic pain and to treat appropriately. Treatment consisted of ultrasound-guided nerve blocks as an initial treatment for neuropathic pain. If long-term pain reduction proved inadequate, peripheral nerve stimulation was offered. Result: After our diagnostic workup consisting of anamnesis, physical examination and imaging, 68 patients out of 105 were diagnosed as having non-neuropathic pain. These patients were referred to the most appropriate consultant, treated accordingly or sometimes pain appeared to be self-limiting. Thirty-seven (35 %) patients were diagnosed as having neuropathic pain with a median NRS of 7 (range 4–9) and were referred for further treatment to our pain clinic. The majority (21 of 28 patients) suffered ileo-inguinal nerve involvement. After ultrasound-guided nerve blocks, a permanent reduction in pain was achieved in 18 patients (62 %) with a median post-treatment NRS of 1 (range 0–3). In six patients to which an additional peripheral nerve stimulator (PNS) was offered, pain reduction to a level of mild complaints with a median NRS of 2 (range 1–8) was observed. In total, 24 of the 28 patients (83 %) diagnosed with neuropathic postherniorrhaphy pain achieved significant pain reduction after algorithm-based treatment. Conclusions: In the present study, we implemented a diagnostic workup for patients with postherniorrhaphy inguinal pain to select those with neuropathic pain. Eighty-three percent of the patients with neuropathic groin pain obtained significant improvement of their pain scores after our protocolled treatment. The effect was achieved by nerve infiltrations and in some cases by an implanted PNS when the former was unsuccessful.

Background: The incidence of chronic pain after endoscopic hernia repair varies between 1 and 16 %. Studies regarding the course of pain in time after the operation are scarce. Methods: 473 male patients ≥18 years of age, scheduled for totally extraperitoneal (TEP) hernia repair (Prolene® mesh) between March 2010 and August 2012 were requested to record pain symptoms preoperative, and 1 day, 1 week, 6 weeks, 3 months and 1 year postoperatively and visit the outpatient department 3 months and 1 year postoperatively for a standardized interview and physical examination. Results: Preoperatively, 25 % (n = 114) of the patients had moderate-to-severe pain (NRS 4–10). Six weeks postoperatively, 3 % (n = 12) of the patients still experienced moderate-to-severe pain. Three months after TEP, only 3 patients (0.6 %) had moderate-to-severe pain, while 83 patients (18 %) experienced mild pain. One year after TEP, 39 patients experienced mild pain (8 %) and 3 patients moderate pain (0.7 %), no patients experienced severe pain after 1 year. Patients with moderate-to-severe pain preoperatively had a higher risk of pain persisting until 3 months and 1 year postoperatively (p = 0.03). In most patients who had pain 3 months postoperatively and were pain-free 1 year after TEP, pain ‘faded out’ at 4–6 months postoperatively. Two patients had a not-painful recurrent hernia, diagnosed 2 and 5 months after TEP repair. Conclusion: Moderate-to-severe pain after TEP hernia repair is self-limiting, with less than 1 % of the patients reporting moderate pain 1 year postoperatively.

Bij thuiswonende ouderen wordt functieverlies mogelijk uitgesteld door preventieve interventies. Het herkennen van ouderen met een verhoogd risico op functieverlies is een belangrijke eerste stap. Dit onderzoek heeft als doelstellingen: (1) om het Identification of Seniors At Risk (ISAR) screeningsinstrument te optimaliseren en te valideren in een eerstelijnspopulatie (ISAR-Primary Care) en (2) om selectie van ouderen met verhoogd risico, vastgesteld met behulp van de ISAR-PC te vergelijken met selectie op basis van alleen leeftijd. In de prospectieve ontwikkelings- en validatiecohorten namen respectievelijk 790 en 2573 thuiswonende ouderen (≥ 70 jaar) deel. Functieverlies was gedefinieerd als minimaal een punt achteruitgang op de gemodificeerde Katz-activiteiten van de dagelijks leven index na twaalf maanden ten opzichte van de score bij inclusie, dan wel sterfte. Drie diagnostische kenmerken waren het meest voorspellend voor functieverlies: leeftijd (odds ratio (OR) 1,06 per toegevoegd jaar; 95 %- BI = 1,02–1,10), afhankelijkheid bij instrumentele activiteiten van het dagelijks leven (OR = 2,17; 95 %-BI = 1,46–3,22), en geheugenproblemen (OR = 2,22; 95 %-BI = 1,41–3,51). Het onderscheidend vermogen uitgedrukt in de AUC-range van de ISAR-PC was 0,67–0,70, en de kalibratie was goed. Van de deelnemende ouderen werd 40,6 % geclassificeerd als ouderen met een verhoogd risico op functieverlies. In het validatiecohort was de AUC range 0,63–0,64. De AUC range van leeftijd ≥ 75 jaar alleen in het validatiecohort was 0,56–0,57 en 65,0 % van de deelnemende ouderen werd daarbij geclassificeerd met een verhoogd risico op functieverlies. Het discriminerend vermogen van de ISAR-PC is redelijk en de kalibratie goed. Selectie van ouderen met een verhoogd risico op functieverlies op basis van ISAR-PC is efficienter dan selectie op basis van alleen leeftijd.

Background Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013–07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. Design This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. Discussion We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. Trial registration The BOOG 2013–07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1613-2) contains supplementary material, which is available to authorized users.

Background: In patients undergoing breast conserving surgery for non-palpable breast cancer, obtaining tumour free resection margins is important to prevent reexcision and local recurrence. We developed a model to predict positive resection margins in patients undergoing breast conserving surgery for non-palpable invasive breast cancer. Methods: A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery in five hospitals in the Netherlands. A prediction model for positive resection margins was developed using multivariate logistic regression. Calibration and discrimination of the model were assessed and the model was internally validated by bootstrapping. Results: Positive resection margins were present in 69/576 (12%) patients. Factors independently associated with positive resection margins included mammographic microcalcifications (OR 2.14, 1.22-3.77), tumour size (OR 1.75, 1.20-2.56), presence of DCIS (OR 2.61, 1.41-4.82), Bloom and Richardson grade 2/3 (OR 1.82, 1.05-3.14), and caudal location of the lesion (OR 2.4, 1.35-4.27). The model was well calibrated and moderately able to discriminate between patients with positive versus negative resection margins (AUC 0.70, 95% CI, 0.63-0.77, and 0.69 after internal validation). Conclusion: The presented prediction model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning and preoperative patient counselling. (C) 2014 Elsevier Ltd. All rights reserved.