Search

Introduction: Postoperative complications impact morbidity and mortality of colon cancer patients. Emerging evidence suggests that intestinal microbiota might play a critical role in the development of postoperative complications after gastrointestinal surgery. Here, we studied changes in fecal microbiota composition comparing samples collected before and after colon cancer surgery. Moreover, we examined whether the microbiota composition before surgery was associated with postoperative complications, and we explored potential determinants of the preoperative microbiota in colon cancer patients. Methods: For this study, two fecal samples were provided by 78 patients with colon cancer. The first (preoperative) sample was collected shortly after diagnosis and before (median and interquartile (IQR) range of 4 (2-6) days) colon cancer surgery. The second (postoperative) sample was collected approximately 6 weeks (median and IQR of 42 (37-47) days) after surgery and before start of adjuvant chemotherapy (whenever applicable). Based on 16S ribosomal RNA gene amplicon sequencing, the fecal microbiota diversity and composition were determined. Preoperative microbiota composition of patients who developed postoperative complications in the 30 days following surgery (n=18, 23%) was compared to those who did not (n=60, 77%) using univariate and multivariate analyses. Explorative random forest analyses were conducted to identify predictors of complication status, with relative abundance of the core genera, sex, age, fecal calprotectin levels, dietary fiber intake, body mass index, smoking status, ASA classification, cancer stage and tumor location being considered as potential predictors. Results: After surgery, microbial alpha diversity was reduced compared to the preoperative situation, whereas compositional changes over time only reached statistical significance for Lachnospiraceae NK4A136 and Coprococcus 1, which both decreased in relative abundance after surgery. Already before the start of surgery, relative abundance of the genera Bacteroides (10% vs 6%) and Lachnoclostridium (0.6% vs 0.2%) appeared to be higher in patients with complications versus those with uncomplicated recovery. In a prediction analysis, current smoking and relative abundance of Lachnoclostridium were identified as most profound predictors of complication status. Fecal calprotectin levels and current smoking status explained most (together 6%) of the overall variation in microbiota composition before surgery. Conclusion: In this study, higher relative abundances of the genera Bacteroides and Lachnoclostridium before surgery were associated with postoperative complications in patients with colon cancer. Future studies should expand on the potential causal and pathogenic routes underlying these observations. Citation Format: Dieuwertje E. Kok, Jannigje G. Kers, Hendriek C. Boshuizen, Niels Klaassen, Henk K. van Halteren, Flip M. Kruyt, Marjolein L. Smidt, Johannes H. De Wilt, Annemarie Boleij, Ellen Kampman, Erwin G. Zoetendal. Pre- and postoperative fecal microbiota and its association with complications after surgery in colon cancer patients. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4380.

Rationale and research objective: As a result of neoadjuvant chemotherapy (NAC), approximately 1/3 of clinically node positive (cN+) breast cancer patients convert to a pathologic complete response (pCR) of the axilla. Targeted Axillary Dissection appears to be most accurate to evaluate axillary treatment-response, but evidence to support this is limited. The RISAS trial was set up to determine the accuracy of sentinel lymph node biopsy (SLNB) combined with excision of the pretreatment marked positive lymph node for axillary staging after NAC in cN+ patients. Methods: This prospective, multicenter trial included cT1-4N1,2,3b patients treated with NAC. Prior to NAC, an iodine seed was placed in the pathologically confirmed positive lymph node. After NAC, all patients underwent SLNB together with excision of the marked lymph node (RISAS-procedure) followed by axillary lymph node dissection (ALND). The identification rate and the accuracy (i.e. false negative rate (FNR) and negative predictive value (NPV)) were calculated for the RISAS procedure. Assuming an FNR of 2%, a prevalence of a positive ALND of 64% and a 10% drop-out rate, a sample size of 248 patients was needed to determine non-inferiority. The NULL hypothesis of inferiority would be rejected at a significance level of 5% if the upper bound of the two-sided 90% Clopper-Pearson confidence interval of the observed FNR would be below the non-inferiority margin of 6.25%. Secondary objectives included the accuracy of the SLNB and excision of the marked lymph node separately. Results: A total of 252 pathologically proven cN+ patients provided informed consent of whom 227 underwent the RISAS procedure/Targeted Axillary Dissection (SLNB combined with excision of the marked positive lymph node). The identification rate of the RISAS procedure is 98% (223/227). Preliminary analysis shows a false negative rate of approximately 5% and a negative predictive value of approximately 91%. Furthermore, by combining SLNB with excision of the marked lymph node, both the identification rate and the accuracy are improved compared to either the SLNB alone or the excision of the marked lymph node alone. Conclusion: This prospective multicenter validation trial shows that the RISAS procedure/Targeted Axillary Dissection is most suitable in terms of identification rate and accuracy to replace ALND for axillary staging after NAC in cN+ patients. The trial was funded by the Dutch Cancer Society (KWF, grant number 2015-8023). Citation Format: Janine Simons, Thiemo JA v Nijnatten, Linetta B Koppert, Carmen C van der Pol, Paul J v Diest, Agnes Jager, David v Klaveren, Boen LR Kam, Marc BI Lobbes, Maaike de Boer, Cees Verhoef, Paul RA Sars, Harold J Heijmans, Els RM van Haaren, Wouter J Vles, Caroline ME Contant, Marian BE Menke, Leonie HM Smit, Wendy Kelder, Marike Boskamp, Ingeborg Mares-Engelberts, Ernest JT Luiten, Marjolein L Smidt. Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer: Results of the prospective multicenter RISAS trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS1-10.

Introduction The COVID-19 pandemic led to a significant drop in the incidence of cancer diagnoses in the Netherlands, partially due to the suspension of all national cancer screening programs on 16th March 2020 (week 12). Hospitals were forced to focus on care for COVID-19 patients resulting in limited capacity and down scaling of health care for non-COVID-19 patients. Specific recommendations for breast cancer treatment strategies, such as alterations in sequence, type, and/or frequency, were temporarily implemented from week 12 onwards. The aim of this study was to investigate the impact of the first outbreak on the initial treatment of breast cancer patients. Methods Women older than 18 years, treated within three months following their breast cancer diagnosis during weeks 2-17 2018-2019 (reference period) or weeks 2-17 2020 (COVID-19 period), were selected from the Netherlands Cancer Registry. Weeks 2-17 2020 were split up in four periods, based on the number of breast cancer diagnoses: weeks 2-8, weeks 9-11, weeks 12-13, and weeks 14-17. Average number of breast conserving surgeries (BCS), mastectomies with direct reconstruction (DR), mastectomies without DR, chemotherapy, endocrine therapy or other therapies, given as initial treatment per week, were calculated, stratified by period and by tumor stage. Treatments given to patients diagnosed in the reference period were compared with treatments given to patients diagnosed in the COVID-19 period, using a Mantel-Haenszel test, adjusting for age. Results A total of 16,553 patients were included in the current study. Of these patients 5,504 received their initial treatment in weeks 2-17 2018, 5,641 in weeks 2-17 2019 and 5,408 in weeks 2-17 2020. An increase in the use of endocrine therapy was seen in weeks 12-13 and 14-17 2020 compared to weeks 2-17 2018/2019, especially for patients with stage I cancer (12.3% and 7.7% vs 4.8%) and stage II cancer (25.4% and 17.4% vs 13.4%). In addition, a lower proportion of patients with stage II breast cancer received chemotherapy as first treatment in weeks 12-13 (21.1%) and 14-17 2020 (20.1%) compared to weeks 2-17 2018/2019 (29.8%) (Table). Discussion The COVID-19 pandemic led to a major increase in the use of endocrine therapy following the recommendations, which was mainly used to enable postponing surgery. The lower use of chemotherapy was probably related to the thought to limit hospital visits and the expected higher risk of developing COVID-19 complications due to chemotherapy. Possible long-term effects of changes in initial treatments will be monitored. Foodnote by table: Weeks 2-17 2020 (the COVID-19 period) were compared to the same weeks in 2018-2019, adjusted for age (74). A statistically significant: ↑ higher proportion of patients received this therapy, corrected for age; ↓ lower proportion of patients received this therapy, corrected for age; a: lower proportion of patients aged between 50 and 64 years received BCS; b: higher proportion of patients aged 39 or younger received mastectomy without DR; c: higher proportion of patients aged 39 or younger, or aged between 50 and 75 years received endocrine therapy; d: higher proportion of patients aged between 40 and 74 years received endocrine therapy; e: higher proportion of patients aged 74 or younger received endocrine therapy; f: higher proportion of patients aged 39 or younger received chemotherapy; g: higher proportion of patients aged 75 years or older received BCS Average number (percentage) initial treatments per week, stratified by stage and periodTotalBreast conserving surgeryMastectomy with direct reconstructionMastectomy without direct reconstructionChemotherapyEndocrine therapyTotalDCISWeek 2-17 2018/201940.629.5 (72.7)4.9 (12.0)5.7 (13.9)0.1 (0.2)0.3 (0.8)0.1 (0.2)Week 2-8 202043.730.9 (70.6)5.0 (11.4)7.3 (16.7)0.4 (1.0)0.1 (0.3)0.0 (0.0)Week 9-11 202038.027.0 (71.1)4.0 (10.5)7.0 (18.4)0.0 (0.0)0.0 (0.0)0.0 (0.0)Week 12-13 202048.031.5 (65.6)7.0 (14.6)7.0 (14.6)0.0 (0.0)2.5 (5.2) ↑0.0 (0.0)Week 14-17 202028.319.0 (67.3)3.0 (10.6)5.8 (20.4) ↑0.0 (0.0)0.5 (1.8)0.0 (0.0)Stage IWeek 2-17 2018/2019146.2104.5 (71.5)10.0 (6.8)17.8 (12.2)6.2 (4.3)7.0 (4.8)0.7 (0.5)Week 2-8 2020148.4107.9 (72.7)7.0 (4.7) ↓15.3 (10.3)10.0 (6.7) ↑7.4 (5.0)0.9 (0.6)Week 9-11 2020131.793.7 (71.1)8.0 (6.1)14.3 (10.9)6.3 (4.8)8.0 (6.1)1.3 (1.0)Week 12-13 2020163.0107.5 (66.0)a10.0 (6.1)20.0 (12.3)b4.5 (2.8)20.0 (12.3)c1.0 (0.6)Week 14-17 2020117.377.0 (65.7) ↓10.8 (9.2)16.8 (14.3)3.3 (2.8)9.0 (7.7) ↑0.5 (0.4)Stage IIWeek 2-17 2018/2019114.937.0 (32.2)5.0 (4.3)20.8 (18.1)34.3 (29.8)15.4 (13.4)2.5 (2.2)Week 2-8 2020116.133.4 (28.8) ↓4.1 (3.6)18.4 (15.9)38.4 (33.1) ↑18.3 (15.7)3.4 (3.0)Week 9-11 2020118.735.7 (30.1)5.7 (4.8)19.0 (16.0)36.0 (30.3)20.0 (16.9)2.3 (2.0)Week 12-13 2020142.042.5 (29.9)5.5 (3.9)26.5 (18.7)30.0 (21.1) ↓36.0 (25.4)d1.5 (1.1)Week 14-17 202083.327.5 (33.0)5.5 (6.6)16.0 (19.2)16.8 (20.1) ↓14.5 (17.4)e3.0 (3.6)Stage IIIWeek 2-17 2018/201931.12.0 (6.3)0.5 (1.7)5.8 (18.5)16.0 (51.5)5.3 (17.0)1.6 (5.0)Week 2-8 202027.92.4 (8.7)0.6 (2.1)5.0 (17.9)14.3 (51.3)4.7 (16.9)0.9 (3.1)Week 9-11 202026.72.0 (7.5)0.3 (1.3)5.7 (21.3)12.7 (47.5)f5.7 (21.3)0.3 (1.3)Week 12-13 202038.52.0 (5.2)0.5 (1.3)7.5 (19.5)19.0 (49.4)8.5 (22.1)1.0 (2.6)Week 14-17 202020.81.5 (7.2)1.3 (6.0) ↑4.5 (21.7)8.0 (38.6)4.5 (21.7)1.0 (4.8)Stage IVWeek 2-17 2018/201915.00.3 (2.3)0.0 (0.2)0.6 (4.0)5.3 (34.9)6.8 (44.9)2.1 (13.7)Week 2-8 202014.60.6 (3.9)0.0 (0.0)0.4 (2.9)4.7 (32.4)6.7 (46.1)2.1 (14.7)Week 9-11 202012.00.0 (0.0)0.0 (0.0)0.0 (0.0)3.3 (27.8)7.0 (58.3)1.3 (11.1)Week 12-13 202019.51.5 (7.7)0.0 (0.0)2.5 (12.8) ↑6.0 (30.8)7.5 (38.5)2.0 (10.3)Week 14-17 202013.80.3 (1.8)g0.0 (0.0)0.3 (1.8)3.8 (27.3)8.3 (60.0) ↑1.3 (9.1) Citation Format: Anouk H Eijkelboom, Linda de Munck, Marie-Jeanne Vrancken Peeters, Marjolein Smidt, Mireille Broeders, Monique Bos, Marjanka K Schmidt, Maud Bessems, Luc Strobbe, Desirée van den Bongard, Aafke Honkoop, Janneke Verloop, Cristina Guerrero Paez, Marc Lobbes, Sabine Linn, Pieter Westenend, Catharina W Menke-van der Houven van Oordt, Jelle Wesseling, Vivianne Tjan Heijnen, Sabine Siesling, On behalve of the NABON COVID-19 consortium. Effect of the COVID-19 pandemic on the initial treatment of breast cancer in the Netherlands: A population-based study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-88.

Background Survival estimates valid at the time of diagnosis are of limited value for (ex-)breast cancer patients who survived several years, as it includes information on already deceased patients. This study analyzed the 10-year conditional risk of recurrent breast cancer in specific prognostic subgroups according to T and N stage and breast cancer subtypes. Secondly, we investigated 10-year conditional overall (OS) and relative survival (RS), adjusted for confounding. Patients and methods We selected all women diagnosed in 2005 with operated T1-2N0-1 breast cancer from the Netherlands Cancer Registry. Patients were classified into T1N0, T1N1, T2N0 and T2N1 stage. Ten-year conditional recurrence rates were calculated for every year from diagnosis for patients without an event (local (LR), regional recurrence (RR), distant metastasis (DM) or death). Ten-year conditional OS was calculated using multivariable Cox regression. RS was estimated by dividing patient survival rates by those of the general Dutch population. Results We included 7,969 patients: 52.3% had T1N0, 15.3% T1N1, 19.9% T2N0 and 12.5% T2N1 stage. For T1N0, 10-year LR rates changed from 4.6% at diagnosis to 0.5% in year 10. RR rates decreased from 2.3% to 0.2% and DM rates decreased from 7.8% to 0.6%. For T2N1 stage, the LR, RR and DM rates decreased from 6.2% to 0.8%, 5.2% to 0.4% and 19.6% to 1.5%, respectively. Of all patients, 1,702 patients (21.4%) had an unknown breast cancer subtype and were consequently excluded from the analyses according to subtype. Of the remaining 6,267 patients, 3,774 (60.2%) had luminal A, 1,465 (23.4%) had luminal B, 314 (5.0%) had HER2 positive and 714 (11.4%) had triple negative disease For the luminal A subtype, LR, RR and DM rates ranged from 3.9% to 0.4%, 1.7% to 0.5% and 7.3% to 1.1%, while for triple negative these rates ranged between 5.6% to 0.7%, 4.9% to 0.2% and 16.7% to 0%, respectively. Differences between subgroups attenuated over time and all recurrence rates became ≤1.5% in year 10. Ten-year OS and RS, adjusted for confounding, showed diminishing risk differences between subgroups over time. Conclusion Differences in recurrence rates, OS and RS between prognostic subgroups decreased as years passed by. These results highlight the importance of taking into account disease-free years to more accurately predict (ex-)breast cancer patients' prognosis over time. Citation Format: van Maaren MC, Strobbe LJ, Smidt ML, Moossdorff M, Poortmans PM, Siesling S. 10-year conditional recurrence risks, overall and relative survival for breast cancer patients in the Netherlands: Taking account of event-free years [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-19.

Background: Her-2-neu receptor (Her2) positive and triple negative breast cancer patients have a poor prognosis. The majority of cancers are characterized as estrogen receptor (ER)+/Her2- and these patients may now have a better prognosis compared to before the introduction of the Her-2-neu receptor. Material and methods: Since 1997 3424 patients were treated for cT1-2N0 breast cancer in three hospitals. Determination of Her2-neu status was introduced between 1999 and 2004. Trastuzumab treatment has been given routinely since 2005. Survival was evaluated for the different groups; ER+/Her2-, ER+/Her2+, ER+/Her2 unknown (status not determined). Results: 2284 patients had ER+/Her2- tumors, 259 had ER+/Her2+ tumors and 262 had ER+/Her2 unknown tumors. Systemic treatment was given to 48.4%, 71.0% and 43.9% respectively. Estimated 5-and 10-year overall survival was 92.0% and 82.2% for ER+/Her2-, 91.6% and 70.8% ER+/Her2+ and 83.4% and 72.2% for ER+/Her2 unknown (p < 0.001). The outcome differences between ER+/Her-2- and ER+/Her-2 unknown tumors remained following adjustment for tumor malignancy grade, nodal status and adjuvant systemic treatment (OR 0.8: CI 0.72 — 0.88; p Discussion: Patients with ER+/Her2- tumors have a significantly better outcome than patients who were classified as ER+ before the assessment of Her-2-neu over-expression. Current prognostic models do not take this effect into account. The branching off of the survival curve for patients with ER+/Her2+ tumors can be explained by the standard use of trastuzumab during the last five years. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-18.

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

Background: The diagnostic work-up and treatment of axillary lymph nodes in breast cancer patients is an ongoing topic of research. The ACOSOG-Z0011 study demonstrated no additional value of complementary axillary lymph node dissection (cALND) in case of limited axillary sentinel lymph node (SLN) metastases in breast cancer patients undergoing breast conserving therapy1. It is questionable whether these results can be applied to patients undergoing a mastectomy2. Trial design: A prospective non-inferiority randomized multicenter trial was designed. Breast cancer patients with cT1-2N0 disease treated with mastectomy and limited axillary SLN metastases will be randomized for follow-up versus complementary axillary treatment. To assess the Quality of Life and morbidity benefits of this experimental treatment, 3 validated questionnaires will be used: QLQ-C30, QLQ-BR 23 and Lymph-ICF3-5. Eligibility criteria: – Women with histological confirmed cT1-2 invasive unilateral breast carcinoma– Clinical node negative: no palpable nodes in physical examination and the axillary ultrasound without signs of lymph node metastases (cyto-/histology if indicated)– Sentinel lymph node biopsy must contain at least one and a maximum of 3 (micro)metastases– Neoadjuvant systemic therapy is allowed Specific aims: Primary endpoint is the axillary recurrence rate. The number of delayed axillary dissections will be registered. Secondary endpoints are distant-disease free survival, overall survival, local recurrence, morbidity and Quality of Life. Statistical methods: Based on 5-year axillary recurrence free survival rate, a failure rate of 0.98 among controls and a true failure rate of 0.96 for study subjects are considered acceptable. Overall, 1114 patients will be included to be able to reject the null hypothesis that the failure rate for experimental and control subjects is inferior by at least 5% (D = −5%) with probability of 0.8 and alpha of 5%. Present accrual and target accrual: This study is expected to start in late 2012 after approval by the Ethical Medical Committee. References 1. Giuliano, A.E., et al., Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA, 2011. 305(6): p. 569–75. 2. Morrow, M. and A.E. Giuliano, To cut is to cure: can we really apply Z11 in practice? Ann Surg Oncol, 2011. 18(9): p. 2413–5. 3. Aaronson, N.K., et al., The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst, 1993. 85(5): p. 365–76. 4. Sprangers, M.A., et al., The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study. J Clin Oncol, 1996. 14(10): p. 2756–68. 5. Devoogdt, N., et al., Lymphoedema Functioning, Disability and Health questionnaire (Lymph-ICF): reliability and validity. Phys Ther, 2011. 91(6): p. 944–57. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-1-03.

Background: Flat Epithelial Atypia (FEA) is a presumably neoplastic alteration of terminal duct-lobular units, characterized by the replacement of native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The architecture shows stratification of epithelial cells. FEA is often accompanied by microcalcifications and therefore discovered in biopsies following screening mammography. FEA is frequently seen in association with ADH (atypical ductal hyperplasia), DCIS (ductal carcinoma in situ), lobular neoplasia and invasive tubular carcinomas. There is emerging evidence suggesting FEA may represent a precursor to DCIS. The risk of subsequent breast carcinoma remains to be defined. The aim of this study is therefore to inventorise the management and outcome of solitary FEA in histological biopsies in three Dutch teaching hospitals. Materials and Methods: Data of this retrospective multicentre study were collected in a database. Local pathology databases were screened with the terms: ‘FEA’, ‘Flat Epithelial Atypia’, ‘columnar atypia’ and Dutch equivalents. Results were manually screened, only including solitary FEA. Patient files were viewed for information on presentation, mammography, ultrasound and management: surgery vs follow-up. In case of excision, definitive pathology was added. Results: We included 103 patients showing only solitary FEA in the primary biopsy. Management of these patients consisted of follow-up for 60 patients (58,3%) and surgery for 43 patients (41,7%, 49 excisions): lumpectomy (42) or mastectomy (7). Reason for choosing mastectomy was preventive in case of contralateral breast cancer or increased familial or genetic risk. Definitive pathology of lumpectomy or mastectomy showed no abnormalities or solitary FEA in 31 patients; other findings were ADH in 7, LCIS in 4 and DCIS in 7 patients. Some patients showed more than one finding. Invasive breast cancer (IBC) was detected in 3 patients. Only one mastectomy showed invasive disease, located in a different lobe, however. No incidents occurred in the follow-up group. Conclusions: No consistent management exists concerning solitary FEA in these three hospitals. Also, one hospital used the diagnosis of FEA inconsistently and interchangingly with other terms. Lack of this study is the retrospective gathering of data, making it difficult to detect the reasons for the chosen management. DCIS or IBC was discovered in 20,4% of all surgical specimens. It was concluded that FEA should be seen as a red flag, indicating the possible presence of a more malignant lesion. Additional research is warranted concerning long term follow-up for this patient group. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-01-13.

Background: The ACOSOG-Z0011 study demonstrated no additional value of complementary axillary lymph node dissection in case of limited axillary sentinel lymph node (SLN) metastases in breast cancer patients undergoing breast conserving therapy1. Since axillary ultrasound can exclude advanced axillary metastatic disease pre-operative2, there is ample opportunity to evaluate whether SLN biopsies are still indicated in a selected group of breast cancer patients. Trial design: A prospective non-inferiority randomized multicenter trial was designed. Breast cancer patients with cT1-2N0 disease, with no evidence for axillary metastases on ultrasound, treated with breast conserving therapy (lumpectomy + whole breast radiotherapy), will be randomized between follow-up and SLN biopsy. If adjuvant systemic therapy is not indicated by tumor or patient characteristics, gene expression profiling may be used for evaluation. To assess Quality of Life, 3 validated questionnaires will be used: QLQ-C30, QLQ-BR 23 and Lymph-ICF3-5. Eligibility criteria: – Women with histological confirmed cT1-2 invasive unilateral breast carcinoma– Clinical node negative: no palpable nodes at physical examination and an axillary ultrasound without signs of lymph node metastases (cyto-/histology if indicated)– Neoadjuvant systemic therapy is allowed. Specific aims: Primary endpoint is the axillary recurrence rate. The number of delayed axillary dissections will be registered. Secondary endpoints are distant-disease free survival, overall survival, local recurrence, morbidity and Quality of Life. Statistical methods: Based on a 5-year axillary recurrence free survival rate: failure rate of 0.99 for controls and a true failure rate of 0.96 (as considered acceptable) for study subjects. Overall, 2086 patients will be included to be able to reject the null hypothesis that the failure rate for experimental and control subjects is inferior by at least 5% (D = −5%) with probability of 0.8 and alpha of 5%. Present accrual and target accrual: This study is expected to start in late 2012 after approval by the Ethical Medical Committee. References 1. Giuliano, A.E., et al., Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA, 2011. 305(6): p. 569–75. 2. Neal, C.H., et al., Can preoperative axillary US help exclude N2 and N3 metastatic breast cancer? Radiology, 2010. 257(2): p. 335–41. 3. Aaronson, N.K., et al., The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst, 1993. 85(5): p. 365–76. 4. Sprangers, M.A., et al., The European Organization for Research and Treatment of Cancer breast cancer-specific quality-of-life questionnaire module: first results from a three-country field study. J Clin Oncol, 1996. 14(10): p. 2756–68. 5. Devoogdt, N., et al., Lymphoedema Functioning, Disability and Health questionnaire (Lymph-ICF): reliability and validity. Phys Ther, 2011. 91(6): p. 944–57. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-1-02.

Introduction - The Netherlands started a nationwide breast cancer screening program in 1989, including women from the age of 50 until 75. Screening mammograms are performed two yearly in a mobile unit and consist of a bilateral two-view mammogram of the breast (mediolateral oblique and craniocaudal views). If indicated, patients are referred to a breast clinic for diagnostic analysis. This work-up consist of among others repeating the bilateral two-view mammogram. Since the screening is digitalized, repeating of at least the mammogram of the non suspicious side might be unnecessary. The aim of this study is to determine the additional value of repeating the contralateral mammogram in patients referred for a suspicious unilateral lesion. Material and methods – 395 patients were referred from breast screening program to our institution for unilateral findings between October 2009 and August 2011. In all patients a bilateral mammogram was repeated and analyzed by an experienced breast radiologist. In the case of breast cancer a breast magnetic resonance imaging (MRI) was performed for preoperative staging. Anonymised data concerning the date of registration of the screening mammogram, the referred side (left/right or bilateral), age, screening's BI-RADS classification, breast density, biopsy results and breast MRI results were collected. Results - Of the 395 patients referred for a suspicious unilateral finding, a malignancy on the referred side was observed in 144 patients (36.5%). In five patients bilateral breast cancer was detected. In one patient no malignancy was detected on the referred side, though on the contralateral side. Three of these six contralateral malignancies were directly mammographically detected. All six malignancies were detected with preoperative breast MRI. Conclusion - Repetition of the two-view mammogram of the contralateral side in patients referred with a unilateral suspicious finding seems unnecessary, since all contralateral malignancies were depicted on the preoperative staging breast MRI recommended according to the EUSOBI-guidelines. Omission of the contralateral mammogram could lead to reduction of associated health care costs, radiation exposure, and patient discomfort caused by the exam. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-02-08.

IntroductionSentinel Lymphnode Biopsy (SLNB) is generally excepted as a minimal invasive technique to stage the axilla in clinically node negative breast cancer patients. Though the reported clinically overt axillary recurrences after negative SLNB is low (0-2,8%), these false negative results after SLNB remain a concern in the treatment of pN0(slnb) breast cancer patients. In this respect many have investigated factors that may influence the risk of developing an axillary recurrence, either to explain the unexpected low incidence or to try to identify subgroups of patients with higher risk of developing an axillary recurrence. Downside to many of these studies is the single-centre study design, mostly presenting small numbers of patients with relatively short follow-up making it difficult to extrapolate the results to the every-day practice.We conducted this multicentre cohort study to identify prognostic factors for developing axillary recurrences after negative SLNB.Patients and MethodsProspectively collected data from seven large volume hospitals in the Netherlands were analyzed. Patients underwent surgery including SLNB between January 2000 and December 2002. Pathological work-up of the sentinel node, local and systemic treatment, and follow-up were performed according to Dutch National guidelines. Statistical analysis was performed to test homogeneity between the institutes. Multivariate analysis was performed to identify prognostic factors. A p-value of 0,2mm) and underwent Axillary Lymphnode Dissection (ALND). In the remaining 1028 patients, 986 (61,7%) were SLN negative and 42 (2,6%) patients were found to have isolated tumor cells (i.e. metastases Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1006.