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1911 Which morphological and molecular parameters can predict the positivity of the nonsentinel axillary lymph node in invasive breast cancer?
Abstracts Material and Methods: 118 consecutive PRs were received from October 2014 to April 2015. The request form included patient age, surgery date, histological tumor type, tumor size, nodes status, ER, PgR, and Ki67. A pathological report was also required. All FFPE samples were reviewed by a pathologist and analyzed in the LAOT, which complies with the standards of a certified quality management system. We described all collected variables, including laboratory turnaround time (TAT), and compared Prosigna® intrinsic subtypes with clinical subtypes based on the St. Gallen 2013 criteria (see Table 1). Results: The PRs came from Spain, Portugal, Lebanon and Egypt. Two PRs (1.7%) did not satisfy the criteria for Prosigna® assay. Two PRs were off-label, just to obtain the intrinsic subtype. According to tumor, the prevalent characteristics were invasive ductal carcinoma (81%), pT1 (79%), pN0 (75%), ER positive (96%), PgR positive (90%)-(PgR20% (86%)), Ki6720% (45.5%). Prosigna® results were 79 (68%) Luminal A, 34 (29%) Luminal B, 3 (3%) Basal-like. The medianTAT was 5 days (range3−17). Globally, we found 67.4% agreement between clinical and Prosigna® intrinsic subtypes (kappa=0.35). The distribution of Prosigna® and clinical subtypes were summarized in Table 1. Conclusions: The Prosigna® test provides clinically relevant information beyond routine clinico-pathological phenotype in breast cancer. IHC subtype might not be an accurate approach for intrinsic subtype and prognosis estimation. No conflict of interest. 1911 POSTER Which morphological and molecular parameters can predict the positivity of the nonsentinel axillary lymph node in invasive breast cancer? O. Bauer1 , R. Georgescu1 , M.F. Coros1 , S. Voidazan2 , I. Colcer1 , D. Moncea3 , C. Moldovan4 , S. Stolnicu3 . 1 Mures County Hospital, General Surgery, Targu Mures, Romania; 2 UMF Targu Mures, Epidemiology, Targu Mures, Romania; 3 UMF Targu Mures, Pathology, Targu Mures, Romania; 4 UMF Targu Mures, Histology, Targu Mures, Romania The aim of the study is to identify the histological and molecular features of the primary invasive breast carcinoma that can predict positivity of the axillary lymph node in order to avoid ALND associated with a high risk of long-time morbidity. Material and Methods: We retrospectively reviewed the invasive breast carcinomas identified in the database (2012–2015) for patients in which ALND was performed. Statistical analysis was done using GraphPad Prism, Fisher‘ and Pearson‘s tests. Results: 133 consecutive patients with invasive breast carcinoma previously diagnosed on a core biopsy were included in the study (mean age 59.35). Presence of axillary metastases in non-sentinel lymph nodes was revealed in 55.63% of the cases, out of which 44.59% were also associated with extra-capsular extension. In this series, the histological type (p = 0.7), grade of the primary tumor (p = 0.145), multifocality (p = 0.49), the presence of an associated in situ component (0.279) and patient’s age (p = 0.699) did not statistically influence the positivity of the non-sentinel axillary lymph nodes. However, we found that the molecular profile of the primary tumor significantly influences the positivity of the non-sentinel axillary lymph nodes (p = 0.0071). Conclusions: Luminal A and Luminal B-Her2 negative tumors have a significantly higher risk for non-sentinel axillary metastasis then other molecular tumor type. No conflict of interest. 1912 POSTER The prognostic value of microarray ERBB2 gene and immunohistochemical stain/FISH of HER2 for early breast cancer patients P.Y. Chen1 , S.H.C. Cheng2 , B.L. Yu3 , C.M. Chen3 . 1 Koo Foundation Sun Yat-Sen Cancer Center, Medical Oncology and Hematology, Taipei City, Taiwan; 2 Koo Foundation Sun Yat-Sen Cancer Center, Radiation Oncology, Taipei City, Taiwan; 3 Koo Foundation Sun Yat-Sen Cancer Center, Surgery, Taipei City, Taiwan Background: Whether microarray test of ERBB2 gene (microarray HER2) correlates with immunohistochemical stain (HER2 IHC) is not conclusive. Material and Methods: We reviewed 672 breast cancer patients treated at our hospital between 2005 and 2012 who met the following criteria, (1) underwent breast surgery, (2) stage I−III, (3) immunohistochemical stain (IHC) for ER, PR, and HER2, (4) Fluorescence In Situ Hybridization (FISH) for HER2 IHC (2+), (5) microarray test for ER, PR, and ERBB2 gene. The definition of HER2 overexpressed breast cancera would be HER2 IHC
S303 (3+) or HER2 IHC(2+) plus amplified FISH. We analyzed the incidence and prognosis of HER2 overexpressed breast cancer patients by traditional IHC/FISH and microarray HER2 test. Results: Total 255 (37.9%) patients with HER2 overexpressed by IHC/FISH were found, including 218 (32.4%) with HER2 IHC (3+) and 37 (5.5%) patients with HER2 IHC(2+) plus FISH(+). Among 255 patients, there were 64 stage I, 116 stage II, and 75 stage III patients. The microarray test showed 182 (27.1%) patients with positive ERBB2 gene. Of these 182 patients, there were 41 stage I, 82 stage II, and 59 stage III patients. There were 172 patients with both positive HER2 IHC/FISH and positive microarray HER2, 83 patients with positive HER2 IHC/FISH but negative microarray HER2, 10 patients with negative HER2 IHC/FISH but positive microarray HER2, and 407 patients with negative HER2 IHC/FISH and negative microarray HER2. Overall, the 5-year PFS in four groups (HER2 IHC/FISH(+) and microarray HER2(+) with Herceptin, HER2 IHC/FISH(+) but microarray HER2(−) with Herceptin, HER2 IHC/FISH(+) and microarray HER2(+) without Herceptin, HER2 IHC/FISH(+) but microarray HER2(−) without Herceptin) were 97.7%, 100%, 70.8%, and 79.3% separately (p = 0.28). For stage II and III patients, the 5-year-PFS in four groups above were 97.3%, 100%, 66%, and 77% separately (p = 0.25). Conclusions: For patients with both positive HER2 IHC/FISH and positive microarray HER2, we found a trend toward worse prognosis if no adjuvant Herceptin treatment. Positive microarray HER2 is as important as positive HER2 IHC/FISH for predicting the effect of adjuvant Herceptin treatment. Negative microarray HER2 may not represent as a prognostic factor as HER2 IHC/FISH because of the intrinsic tumor heterogeneity. No conflict of interest. 1913 POSTER Pre and post neoadjuvant endocrine therapy (NET) biomarkers in breast cancer to better predict distant progression: A retrospective study R. Montal1 , G. Rivas1 , A. Petit2 , T. Soler2 , J. Perez3 , I. Morilla1 , A. Guma4 , M.J. Pla5 , M. Gil1 . 1 Institut Catala` d’Oncologia, Medical Oncology, Barcelona, Spain; 2 Hospital de Bellvitge, Anatomical Pathology, Barcelona, Spain; 3 Institut Catala` d’Oncologia, Clinical Investigation Unit, Barcelona, Spain; 4 Hospital de Bellvitge, Radiology, Barcelona, Spain; 5 Hospital de Bellvitge, Gynecology, Barcelona, Spain Background: NET is gaining more acceptances for the management of locally advanced ER positive breast cancer, not only for elderly or frail individuals. Ellis et al reported the preoperative endocrine prognostic index in which pathological tumor size, node status, Ki67 level, and ER status were independently associated with relapse free survival. The aim of our study is to validate and discover new biomarkers in the surgery specimen after NET that could be useful for the clinicians in the decision-making of adjuvant treatment. Material and Methods: We designed a retrospective study of 119 ER/PR positive breast cancer (stage II and III) in postmenopausal woman that were treated with neoadjuvant endocrine therapy (AI 64%, SERM 36%) during a median time of 8.5 months before surgery from 1997 to 2009 in Institut Catala` d’Oncologia. Adjuvant chemotherapy, radiotherapy and endocrine therapy were received by 7%, 76% and 96% of the patients respectively. Were analyzed ER, PR and Ki67 in the surgical specimen through a tissue microarray and the results were compared with the values before starting NET. Also were studied other clinical factors like TNM staging, histological grade (HG), vascular invasion and treatment response. The survival analysis was performed using Kaplan–Meier method, and the results were examined using the log-rank test. For multivariate statistical analyses a Cox regression model was carried out. Results: With a median follow-up of 80 months after surgery 21 patients developed metastatic recurrence. The median overall survival of all patients was 139 months [95% CI = 98–181]. Univariate analysis for time to distant progression showed statistically significant differences in pN stage (P = 0.01), cN stage (P = 0.012), HG after NET (P = 0.02), PR before NET (P = 0.023) and vascular invasion in the surgical specimen (P = 0.036). On the other hand, no differences were observed in relation to T stage, treatment response (clinical and radiological) and in changes (baseline vs surgery) of ER, PR and Ki67%. Multivariate testing revealed that HG after NET was independently associated with time to distant progression (HR = 0.078, 95% CI = 0.010– 0.607). Patients with HG 3 after NET had a poor prognosis, having died from cancer 11 of 30. In this context, only 2 patients were treated with adjuvant chemotherapy but none of them have relapsed.
S303 (3+) or HER2 IHC(2+) plus amplified FISH. We analyzed the incidence and prognosis of HER2 overexpressed breast cancer patients by traditional IHC/FISH and microarray HER2 test. Results: Total 255 (37.9%) patients with HER2 overexpressed by IHC/FISH were found, including 218 (32.4%) with HER2 IHC (3+) and 37 (5.5%) patients with HER2 IHC(2+) plus FISH(+). Among 255 patients, there were 64 stage I, 116 stage II, and 75 stage III patients. The microarray test showed 182 (27.1%) patients with positive ERBB2 gene. Of these 182 patients, there were 41 stage I, 82 stage II, and 59 stage III patients. There were 172 patients with both positive HER2 IHC/FISH and positive microarray HER2, 83 patients with positive HER2 IHC/FISH but negative microarray HER2, 10 patients with negative HER2 IHC/FISH but positive microarray HER2, and 407 patients with negative HER2 IHC/FISH and negative microarray HER2. Overall, the 5-year PFS in four groups (HER2 IHC/FISH(+) and microarray HER2(+) with Herceptin, HER2 IHC/FISH(+) but microarray HER2(−) with Herceptin, HER2 IHC/FISH(+) and microarray HER2(+) without Herceptin, HER2 IHC/FISH(+) but microarray HER2(−) without Herceptin) were 97.7%, 100%, 70.8%, and 79.3% separately (p = 0.28). For stage II and III patients, the 5-year-PFS in four groups above were 97.3%, 100%, 66%, and 77% separately (p = 0.25). Conclusions: For patients with both positive HER2 IHC/FISH and positive microarray HER2, we found a trend toward worse prognosis if no adjuvant Herceptin treatment. Positive microarray HER2 is as important as positive HER2 IHC/FISH for predicting the effect of adjuvant Herceptin treatment. Negative microarray HER2 may not represent as a prognostic factor as HER2 IHC/FISH because of the intrinsic tumor heterogeneity. No conflict of interest. 1913 POSTER Pre and post neoadjuvant endocrine therapy (NET) biomarkers in breast cancer to better predict distant progression: A retrospective study R. Montal1 , G. Rivas1 , A. Petit2 , T. Soler2 , J. Perez3 , I. Morilla1 , A. Guma4 , M.J. Pla5 , M. Gil1 . 1 Institut Catala` d’Oncologia, Medical Oncology, Barcelona, Spain; 2 Hospital de Bellvitge, Anatomical Pathology, Barcelona, Spain; 3 Institut Catala` d’Oncologia, Clinical Investigation Unit, Barcelona, Spain; 4 Hospital de Bellvitge, Radiology, Barcelona, Spain; 5 Hospital de Bellvitge, Gynecology, Barcelona, Spain Background: NET is gaining more acceptances for the management of locally advanced ER positive breast cancer, not only for elderly or frail individuals. Ellis et al reported the preoperative endocrine prognostic index in which pathological tumor size, node status, Ki67 level, and ER status were independently associated with relapse free survival. The aim of our study is to validate and discover new biomarkers in the surgery specimen after NET that could be useful for the clinicians in the decision-making of adjuvant treatment. Material and Methods: We designed a retrospective study of 119 ER/PR positive breast cancer (stage II and III) in postmenopausal woman that were treated with neoadjuvant endocrine therapy (AI 64%, SERM 36%) during a median time of 8.5 months before surgery from 1997 to 2009 in Institut Catala` d’Oncologia. Adjuvant chemotherapy, radiotherapy and endocrine therapy were received by 7%, 76% and 96% of the patients respectively. Were analyzed ER, PR and Ki67 in the surgical specimen through a tissue microarray and the results were compared with the values before starting NET. Also were studied other clinical factors like TNM staging, histological grade (HG), vascular invasion and treatment response. The survival analysis was performed using Kaplan–Meier method, and the results were examined using the log-rank test. For multivariate statistical analyses a Cox regression model was carried out. Results: With a median follow-up of 80 months after surgery 21 patients developed metastatic recurrence. The median overall survival of all patients was 139 months [95% CI = 98–181]. Univariate analysis for time to distant progression showed statistically significant differences in pN stage (P = 0.01), cN stage (P = 0.012), HG after NET (P = 0.02), PR before NET (P = 0.023) and vascular invasion in the surgical specimen (P = 0.036). On the other hand, no differences were observed in relation to T stage, treatment response (clinical and radiological) and in changes (baseline vs surgery) of ER, PR and Ki67%. Multivariate testing revealed that HG after NET was independently associated with time to distant progression (HR = 0.078, 95% CI = 0.010– 0.607). Patients with HG 3 after NET had a poor prognosis, having died from cancer 11 of 30. In this context, only 2 patients were treated with adjuvant chemotherapy but none of them have relapsed.