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Purpose: Our purpose was to assess the prevalence of patient-reported symptoms of local late toxicity in patients with irradiated breast cancer and determine the association between late toxicity and quality of life. Methods: Within the prospective Utrecht cohort for Multiple BReast cancer intErvention studies and Long-term evaluation cohort, a survey on self-reported late toxicity was sent to all patients with breast cancer with ≥12 months interval since radiation therapy treated with curative intent. Patients were treated with hypofractionated radiation therapy of 40 Gy/15 fractions or 42.5 Gy/16 fractions, with or without a simultaneous integrated boost. Symptoms of late toxicity were evaluated on a 4-point Likert scale. Late toxicity was defined as moderate-severe breast or chest wall pain combined with at least 1 other mild-severe late toxicity symptom, that is, breast or arm/hand lymphedema, firmness of the breast, or impaired arm movement. Physical, role, and social functioning were measured before, during, and after the late toxicity survey using the European Organization for Research and Treatment of Cancer Quality of Life Core questionnaire-C30 and compared with a Dutch normative population. Results: In the study, 1613/2248 patients (72%) were included. Of those, 16% (n = 265) reported late toxicity. The median time interval between radiation therapy and survey was 38 months (interquartile range, 21-55). Moderate/severe firmness of the breast, chest wall pain, and breast pain were reported by, respectively, 18% (n = 295), 14% (n = 225), and 10% (n = 140) of all patients. Physical, role, and social functioning were below the clinical threshold (ie, clinically relevant impairment) in 13% to 52% of patients with late toxicity and 2% to 26% of patients without late toxicity. Patients with late toxicity significantly more often received analgesics, physiotherapy, and lymphedema therapy compared with patients without late toxicity. Conclusions: This study provided insight into the prevalence of patient-reported late toxicity after hypofractionated radiation therapy and the influence of late toxicity on quality of life after breast cancer. These results may help health care professionals to inform their patients about long-term effects of breast cancer treatment including hypofractionated radiation therapy.

Background: Among elderly breast cancer patients, endocrine therapy may be chosen as definitive treatment by patients or physicians. This study investigated the efficacy of endocrine monotherapy (ET) in terms of avoidance of invasive local treatment. Methods: Elderly patients (≥70 years) with a diagnosis of estrogen receptor-positive breast cancer who underwent ET between 2008 and 2015 were identified through the Netherlands Cancer Registry. The primary outcome was the cumulative risk of undergoing invasive local treatment (radiotherapy or surgery) for the primary tumor. The secondary outcomes were development of uncontrolled local disease and overall survival (OS). Results: Of the 105 patients (median age, 86 years) enrolled in this study, 91 (78 %) received ET as definitive treatment, whereas 14 received ET as a “bridge to surgery.” For the 91 patients who used ET as intended definitive treatment, the 5-year cumulative risk of undergoing invasive local treatment and experiencing uncontrolled disease were respectively 28 % and 16 %. The 5-year cumulative OS was 42 %. Whereas 11 patients had metastatic or locally progressive breast cancer at the time of death, cardiovascular disease, infectious diseases, and old age or dementia were reported as contributing to the death of 39 patients. Conclusions: For a select group of elderly breast cancer patients who received sustained ET, the risk of undergoing invasive local treatment was surpassed by a twofold higher risk of dying. As an alternative to invasive local treatment, ET can be discussed as a safe and effective option for patients unwilling or unfit to undergo surgery.

Purpose Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making. Methods In the IKA trial, postmenopausal patients with non-metastatic breast cancer had been randomized between no or limited adjuvant tamoxifen treatment without receiving chemotherapy. For this secondary analysis, FFPE tumor material was obtained of ER+HER2− patients with 0–3 positive lymph nodes and tested for the 70-gene signature. Distant recurrence-free interval (DRFI) long-term follow-up data were collected. Kaplan–Meier curves were used to estimate DRFI, stratified by lymph node status, for the three predefined 70-gene signature risk groups. Results A reliable 70-gene signature could be obtained for 135 patients. Of the node-negative and node-positive patients, respectively, 20% and 13% had an ultralow-risk classification. No DRFI events were observed for node-negative patients with an ultralow-risk score in the first 10 years. The 10-year DRFI was 90% and 66% in the low-risk (but not ultralow) and high-risk classified node-negative patients, respectively. Conclusion These survival analyses indicate that the postmenopausal node-negative ER+HER2− patients with an ultralow-risk 70-gene signature score have an excellent 10-year DRFI after surgery with a median of 1 year of endocrine treatment. This is in line with published results of the STO-3-randomized clinical trial and supports the concept that it is possible to reduce the duration of endocrine treatment in selected patients.

Background The percentage of older patients undergoing surgery for early-stage breast cancer has decreased over the past decade. This study aimed to develop a prediction model for postoperative complications to better inform patients about the benefits and risks of surgery, and to investigate the association between complications and functional status and quality of life (QoL). Methods Women aged at least 70 years who underwent surgery for Tis-3 N0 breast cancer were included between 2013 and 2018. The primary outcome was any postoperative complication within 30 days after surgery. Secondary outcomes included functional status and QoL during the first year after surgery, as assessed by the Groningen Activity Restriction Scale and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 questionnaires. A prediction model was developed using multivariable logistic regression and validated externally using data from the British Bridging the Age Gap Study. Linear mixed models were used to assess QoL and functional status over time. Results The development and validation cohorts included 547 and 2727 women respectively. The prediction model consisted of five predictors (age, polypharmacy, BMI, and type of breast and axillary surgery) and performed well in internal (area under curve (AUC) 0.76, 95 per cent c.i. 0.72 to 0.80) and external (AUC 0.70, 0.68 to 0.72) validations. Functional status and QoL were not affected by postoperative complication after adjustment for confounders. Conclusion This validated prediction model can be used to counsel older patients with breast cancer about the postoperative phase. Postoperative complications did not affect functional status nor QoL within the first year after surgery even after adjustment for predefined confounders. Lay summary Surgery remains the standard of care for the majority of older patients with breast cancer. The percentage of older patients with breast cancer receiving surgery is decreasing. The reason for this decline is unknown, but it might be due to fear of complications. To better inform patients about the benefits and risks of surgery, the aim of this study was to develop a prediction model for complications after surgery. Another important aspect, especially for older adults with breast cancer, is quality of life, functional capacity, and ability to carry out daily tasks (functional status) after therapy. This study showed that quality of life and functional status did not decline after breast surgery, irrespective of the occurrence of postoperative complications.Some 41.0 per cent of older patients with breast cancer developed a postoperative complication within 30 days after surgery. The authors designed a prediction tool that can predict complication risk, with a good internal and external validity. Postoperative complications did not affect functional status or quality of life in the first year after surgery after adjustment for confounders.

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.

Among elderly breast cancer patients, endocrine therapy may be chosen as definitive treatment by patients or physicians. This study investigated the efficacy of endocrine monotherapy (ET) in terms of avoidance of invasive local treatment.Elderly patients (≥70 years) with a diagnosis of estrogen receptor-positive breast cancer who underwent ET between 2008 and 2015 were identified through the Netherlands Cancer Registry. The primary outcome was the cumulative risk of undergoing invasive local treatment (radiotherapy or surgery) for the primary tumor. The secondary outcomes were development of uncontrolled local disease and overall survival (OS).Of the 105 patients (median age, 86 years) enrolled in this study, 91 (78 %) received ET as definitive treatment, whereas 14 received ET as a "bridge to surgery." For the 91 patients who used ET as intended definitive treatment, the 5-year cumulative risk of undergoing invasive local treatment and experiencing uncontrolled disease were respectively 28 % and 16 %. The 5-year cumulative OS was 42 %. Whereas 11 patients had metastatic or locally progressive breast cancer at the time of death, cardiovascular disease, infectious diseases, and old age or dementia were reported as contributing to the death of 39 patients.For a select group of elderly breast cancer patients who received sustained ET, the risk of undergoing invasive local treatment was surpassed by a twofold higher risk of dying. As an alternative to invasive local treatment, ET can be discussed as a safe and effective option for patients unwilling or unfit to undergo surgery.

Background Pre-test genetic counseling for patients with breast cancer is increasingly being provided by nongenetic healthcare professionals. We evaluated the attitudes, knowledge, and self-efficacy of surgeons, oncologists, and nurses regarding mainstream genetic testing and the feasibility to incorporate pre-test genetic counseling into routine care. Methods We offered an online training to healthcare professionals from 13 hospitals and implemented a mainstream genetic testing pathway in 11/13 (85%) hospitals. Questionnaires were sent before (T0) and 6 months after (T1) completing the training. Those who did not complete the training received a questionnaire to assess their motivations. Results In 11 hospitals, 80 (65%) healthcare professionals completed the training, of whom 70 (88%) completed both questionnaires. The attitudes, (perceived) knowledge and self-efficacy of healthcare professionals were high both at baseline and 6 months after completing the training. After 6 months, their perceived knowledge about the advantages and disadvantages of a genetic test and implications for family members had significantly improved (p = 0.012 and p = 0.021, respectively). For the majority (89%), the time investment for pre-test genetic counseling was less than 15 min per patient and as expected or better. Healthcare professionals considered the total time investment feasible to incorporate mainstream genetic testing into their daily practice. The main barrier to complete the training was lack of time. The online training was considered useful, with a rating of 8/10. Conclusion Surgical oncologists and nurses in breast cancer care feel well-equipped and motivated to provide pre-test genetic counseling after completion of an online training module.

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.

Additional file 1. Data management plan.

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.