194P Comparisons of tumor-infiltrating lymphocytes and 21-gene recurrence score in ER-positive/HER2-negative breast cancer S.G. Ahn1 , Y.J. Cha2 , C. Yoon1 , S.J. Bae1 , J. Kim3 , J. Jeong1 1
Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea,2
Pathology, Gangnam Severance Hospital, Seoul, Republic of Korea, 3
Surgery, Kangnam Mizmedi Hospital, Seoul, Republic of Korea
Background: Recent meta-analysis showed that tumors with high tumor-infiltrating lymphocyte (TIL) have a higher probability of pathologic complete response even in Luminal/HER2-negative breast cancer. Also, the 21-gene recurrence score (RS) predicts the clinical benefit of chemotherapy for ER-positive/HER2-negative women. We com-pared two markers in those cancer.
Methods: In ER-positive/HER2-negative patients treated with primary surgery, the RS (Oncotype DXVRBreast Cancer Assay; Genomic Health, Inc., USA) was obtained. We evaluated TIL in H&E slides of surgical specimens by standardized methodology pro-posed by the international TIL-working group. In 198 women, the percentage of stro-mal TIL was successfully assessed. In accordance with the recent meta-analysis, the degree of TILs were categorized as high ( >¼60%), intermediate (11-59%), and low ( <¼10%).
Results: Ninety-seven (49.0%), 88 (44.4%), and 13 patients (6.6%) had low, intermedi-ate, and high TILs, respectively. There is a significant but weak correlation between con-tinuous RS and concon-tinuous TIL (Pearson’s R¼ 0.201, P ¼ 0.004). The average of continuous RS was significantly highest in the high TIL tumors (17.8610.7 in low TIL, 19.468.7 in intermediate TIL, and 26.268.2 in high TIL; P¼ 0.014). Whereas the aver-age of continuous TILs was compared according to categorized RS, it was significantly higher in the intermediate RS or the high RS tumors (15.4613.2 in low RS, 26.6613.6 in intermediate RS, and 19.8619.2 in high RS; P < 0.001). When we compared catego-rized RS and TIL, we found that the rates of the high TIL-tumors was significantly higher in the intermediate RS or the high RS (1.0% for low RS tumors, 12.5% for inter-mediate RS tumors, and 10.0% for high RS tumors; P¼ 0.007).
Conclusions: We found that tumors with high TIL tend to have a higher RS in ER-positive/HER2-negative breast cancer. We also noted that the rate of high-TIL tumors was significantly higher in the intermediate-RS tumors as well as in the high-RS tumors. Clinically, our findings suggest that TIL count might be referred in decision-making of chemotherapy in the intermediate RS-patients.
Legal entity responsible for the study: N/A
Funding: This research was supported by the Basic Science Research Program through the NRF, funded by the Ministry of Science, ICT, & Future Planning (NRF-2015R1C1A1A02037104), and grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (1520120). Disclosure: All authors have declared no conflicts of interest.
195P The 70-gene signature in node positive breast cancer: 10-year
follow-up of the observational RASTER study S.B. Vliek1 , V. Retel2 , C. Drukker3 , J.M. Bueno-De-Mesquita1 , E. Rutgers3 , H. van Tinteren4 , M.J. van de Vijver5 , J. Wesseling6 , W. van Harten2 , S.C. Linn7 1
Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands,
2
Health Technology Assessment, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands,3
Surgical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands,
4
Biometrics, The Netherlands Cancer Institute, Amsterdam, Netherlands,5
Pathology, Academic Medical Center, Amsterdam, Netherlands,6
Pathology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands,7
Medical Oncology, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands
Background:In early stage breast cancer patients, with axillary lymph node metastasis, the 70-gene signature, MammaPrintVR(MP) identifies patients with a High or Low Risk of distant breast cancer (BC) recurrence. For MP Low Risk (G(enomic)-low) in pa-tients with up to 3 positive lymph nodes (N1-3), the MINDACT trial (Cardoso, NEJM 2016) showed that it might be safe to forgo adjuvant chemotherapy. Here we evaluated the prognostic value of MP at 10 years follow-up in patients with lymph node positive early stage BC.
Methods:Between 2004 and 2006 812 women with early stage BC participated in the observational RASTER trial (Bueno de Mesquita, Lancet Oncol, 2007). 181 patients
were node positive and not included in the primary analysis, 176 of them gave consent for future research. On 164 tumor samples (FFPE) MP was performed retrospectively. Survival data was collected and samples were allocated to clinical high (high) or C-low risk as used in MINDACT. Patients with over 3 axillary lymph node metastases (N4þ) were all considered C-high. 10-year distant-recurrence-free-interval (DRFI) was compared between subgroups based on the MP and clinical assessment.
Results:In 3 patients the clinical assesment could not be determined. Over 95% of
pa-tients received chemotherapy, 82.9% (136/164) of tumors were ER-positive and 18.3% (30/164) of patients had N4þ. MP identified 47% (n ¼ 77/164) as Low Risk, including 16,9% (13/77) with N4þ. 10-year DRFI in patients N1-3 and G-Low or G-High was 94.9% and 80.7% respectively (HR 4.7; 95%CI 1.3-16.2). With the clinical assessment 13.7% (n¼ 22/161) were low risk, only one was diagnosed with distant BC recurrence. 10-years DRFI was 94.4% in C-low and 85.8% in C-high (HR 3.7 95%CI 0.5-28.5). In N4þ 10-years DRFI was 69.7%. Combining the clinical assessment with MP risk assess-ment in patients N1-3 the 10-years DRFI in clinical high risk patients was 95.2% for G-Low (n¼ 44) and 79.6% for G-High (n ¼ 65) (HR 4.83 95%CI 1.1-21.4).
Conclusions:We again confirm the prognostic value of Mammaprintin BC patients with axillary lymph node involvement after 10 years follow up. In N1-3 patients with clinical high risk, MP can identify a subgroup with excellent prognosis after standard adjuvant systemic therapy.
Legal entity responsible for the study:S. Linn
Funding:None
Disclosure:All authors have declared no conflicts of interest.
196P Higher expression of estrogen response genes in the primary tumor is associated with a greater risk for late recurrence in patients with ER1/ HER2-breast cancer
R.D. Bense, E.G.E. de Vries, C.P. Schro¨der, R.S.N. Fehrmann
Department of Medical Oncology, University Medical Center Groningen, Groningen, Netherlands
Background: In patients with ERþ breast cancer, 50% of recurrences occur > 5 years after diagnosis (i.e. late recurrence). Clinical trials report contradicting results on the ef-fect of extended endocrine therapy > 5 years to reduce late recurrence risk. Using publi-cally available breast cancer gene expression profiles, we aimed to gain insight into the biology that increases the risk for late recurrences.
Methods: Gene expression profiles of primary ERþ/HER2- tumors of breast cancer pa-tients were collected with disease-free survival (DFS) data, defined as time of diagnosis to local recurrence or distant metastasis. We defined (i) a group containing all patients (n¼ 2,231), (ii) a group that received 5 years of endocrine therapy only (n ¼ 591), and (iii) a group that received no systemic therapy (n¼ 497). For each group, genes were ranked on their association with DFS as determined by multivariate Cox regression with age, tumor size, grade, lymph node status, and therapy as covariates. Gene set en-richment analysis (GSEA) was performed on these gene lists with the Hallmark collec-tion from the Molecular Signatures Database. Within each group, associacollec-tions with early recurrence were studied in all patients with censoring at 5 years if no event occurred < 5 years after diagnosis (set I). To study associations with late recurrence, a second set was defined that contained only patients with a follow-up 5 years and no event < 5 years after diagnosis (set II).
Results: Within all patients and the group that received 5 years of endocrine treatment only, higher expression of genes belonging to the Hallmark ‘estrogen response late’ was associated with longer DFS in set I and shorter DFS in set II. This Hallmark contains es-trogen responsive genes identified in estradiol treated ERþ breast cancer cell lines. However, in patients who received no systemic treatment, higher expression of these genes was associated with shorter DFS in both set I and II.
Conclusions: Higher expression of estrogen response genes is associated with a greater risk for late recurrence in patients with ERþ/HER2- breast cancer. Potentially, patients with ERþ tumors with high expression of these genes might benefit most from ex-tended endocrine therapy.
Legal entity responsible for the study: R.S.N. Fehrmann
Funding: Dutch Cancer Society grants RUG 2010-4739 and RUG 2013-5960, NWO-VENI grant (916-16025) and a Mandema Stipendium.
Disclosure: All authors have declared no conflicts of interest.
197P Understanding BRCA1 and BRCA2 mutated breast cancer cases in Romania: First report on founder mutations in Romanians A. Eniu1 , L. Pop2 , A. Stoian1 , E. Dronca2 , R. Matei1 , M. Ligtenberg3 , H. Ouchene3 , A. Onisim1 , O. Rotaru1 , R. Eniu4 , N. Antone1 1
Department of Breast Tumors, Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania, 2
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, 3
Department of Human Genetics, Radboud University Medical Centre, Nijmegen, Netherlands,4
School of Medicine, Cardiff University, Cardiff, UK
Background: First systematic analysis of BRCA 1(B1) or BRCA2(B2) mutations in high-risk Romanian breast cancer patients (pts) aiming at defining founder mutations.
