Hanna, Helena

PURPOSE The feasibility of Oncotype DX Breast Recurrence Score testing on diagnostic core needle biopsy (CNB) samples has been demonstrated through analysis of a large central laboratory experience. However, concordance with paired samples from the same primary breast tumor has not been comprehensively evaluated. The primary objective of this study was to determine the degree of concordance of Recurrence Score (RS) results between paired CNB and surgical excision (SE) specimens from the same untreated primary breast tumor of patients with early-stage, hormone receptor–positive, human epidermal growth factor receptor 2–negative invasive breast cancer. MATERIALS AND METHODS Patients with a clinical RS result on either a CNB or SE specimen were included. Lin concordance correlation coefficient (CCC) with 95% CIs was estimated to assess agreement of continuous RS results between paired samples. Cohen Kappa with 95% CIs was used to evaluate categorical RS result concordance. RESULTS A total of 134 patients were identified with paired CNB and SE specimens. The median age was 62 years (range, 33-99; 23 patients [17%] were age ≤50 years v 111 [83%] age >50 years). The mean RS results were 15.6 (range, 0-56) for CNB and 16.6 (range, 0-59) for SE ( P = .003), with no statistically significant differences in RS categories. Agreement between continuous RS results from paired samples was strong, with a Lin CCC of 0.86 (95% CI, 0.80 to 0.90). The overall percent agreement in RS categories was 91.8% (95% CI, 87.1 to 96.4). Categorical agreement was further supported by a Cohen Kappa statistic of 0.64 (95% CI, 0.44 to 0.83), indicating substantial agreement between CNB and SE specimens. CONCLUSION The results of this study demonstrate high concordance of RS results between paired samples, which supports the use of CNB for Oncotype DX testing.

Abstract INTRODUCTION: The Oncotype DX Breast Recurrence Score® (RS) assay is validated to predict risk of distant recurrence at 10 years and the benefit of adjuvant chemotherapy in patients with estrogen receptor (ER)+, HER2- early breast cancer who receive 5 years of endocrine therapy. The feasibility of Oncotype DX® testing with diagnostic core needle biopsies (CNB) was demonstrated through analysis of a large commercial laboratory experience. The neoadjuvant ADAPT study showed the clinical utility of deriving the Recurrence Score® (RS) result from CNB as well. However, data are limited on concordance of RS results from paired CNB and surgical samples. Our primary objective was to determine the degree of concordance of RS results between paired tissue samples from the same primary breast tumor of patients with early stage, ER+, HER2- invasive breast cancer who had a CNB and subsequent surgical excision (SE; lumpectomy or mastectomy) without intervening systemic therapy. METHODS: Patients with a commercial RS result on either CNB or subsequent SE were identified through medical record and clinical database review. A pathologist reviewed archival tissue samples to confirm eligibility and selected the other paired CNB or SE block most representative of the tumor tissue for subsequent study Oncotype DX testing. Descriptive statistics were used to summarize patient and tumor characteristics. Wilcoxon signed rank, McNemar’s and Cochran-Mantel-Haenszel tests were used to compare RS between SE and CNB paired samples. Cohen’s Kappa and 95% confidence intervals (CIs) were used to compare the agreement of categorical RS (0-25 and 26-100) result between SE and CNB paired samples. Lin’s concordance correlation and 95% CIs were used to compare agreement of continuous RS between paired samples. RESULTS: A total of 134 patients were identified with paired CNB and SE samples with a median time of 34 (range 5-103) days between collections. Of the 134 patients, a commercial RS result was available for 25 (18.7%) with CNB and 109 (81.3%) with SE. A study RS result was then generated on the other paired sample. Median age was 62 years (range 33-99; 23 patients [17%] were age ≤50 vs. 111 [83%] age >50). Cases were predominantly node negative (107/134 node negative vs. 26/134 node positive; 1/134 unknown) invasive ductal carcinomas (104/134 ductal vs. 18/134 classic lobular vs. 12/134 other). Mean RS results were 15.6 (range 0-56) and 16.6 (range 0-59) for CNB and SE, respectively (p = 0.003), with no statistically significant differences in RS category defined as low vs. high risk (119/134 CNB vs. 114/134 SE for RS 0-25 and 15/134 CNB vs 20/134 SE for RS 26-100; p = 0.13) or low vs. intermediate vs. high risk (85/134 CNB vs. 78/134 SE for RS 0-17 and 43/134 CNB vs. 48/134 SE for RS 18-30 and 6/134 CNB vs. 8/134 SE for RS 31-100; p = 0.19). No differences were observed based on age relative to 50 years or nodal status (data not shown). Cohen’s Kappa statistic k = 0.64 (95% CI, 0.44-0.83) supports substantial agreement between the CNB and SE samples. Lin’s concordance correlation coefficient (CCC) demonstrates similar agreement for the continuous RS result between paired samples (CCC = 0.86 [0.80-0.90]). Overall percent agreement was 91.8% (87.1-96.4%). CONCLUSIONS: Studies evaluating the level of concordance of ER, progesterone receptor, and HER2 biomarker status between CNB and SE samples have found high concordance rates, albeit varied. We now provide data demonstrating high concordance of RS results between CNB and SE specimens obtained from the same breast primary tumor without intervening systemic therapy. This supports use of either biopsy source for testing with a genomic predictor to identify those patients who will most likely benefit from chemotherapy and which patients may be spared. Citation Format: Aziza Nassar, Jodi Carter, Paige Innis, Satish Seerapu, Christy Russell, Helena Hanna, Abigail Lochala, Minetta Liu. Concordance analysis of paired breast cancer core needle biopsies and surgical excision samples using the Oncotype DX Breast Recurrence Score® assay [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-08-09.

Objectives: Herein, we present the PancreaSeq® results of 28 patients and emphasize the usefulness of molecular testing in evaluation of pancreatic cysts. Material and Methods: A total of 10 (35.7%) non-diagnostic, 6 (21.4%) negative, 5 (17.8%) atypical, and 7 (25%) were positive for mucinous cystic neoplasm (MCN) pancreatic cyst aspirates were analyzed with PancreaSeq® at Mayo Clinic, Jacksonville between September 2021 and February 2023. Results: Three non-diagnostic, two negative, three atypical, and two positive for MCN cysts were positive for KRAS and GNAS mutations. They were interpreted as intraductal papillary mucinous neoplasm (IPMN) with low risk for progression to high-grade dysplasia/adenocarcinoma. One negative case was positive for KRAS and GNAS mutation and RNF43 copy number alteration. It was interpreted as IPMN with a low risk of progression. Two non-diagnostic, one negative, and two positive for MCN cysts were positive for KRAS mutation. All were interpreted as IPMN/MCNs with low risk of progression. One positive for MCN case was positive for GNAS mutation and ALK fusion and one positive for MCN case was positive for GNAS mutation, ALK fusion, and RNF43 copy number alteration. Both were interpreted as IPMN and their risk of progression was interpreted as not well understood. One atypical case was positive for KRAS and TP53 mutation and was interpreted as IPMN/ MCNs with a high risk of progression. VHL mutation was present in one non-diagnostic case. It was interpreted as serous cystadenoma and the risk for progression was low. Conclusion: Molecular analysis of pancreatic cysts with PancreaSeq® is useful in accurate diagnosis, especially when cytologic material is non-diagnostic and helps improve patient management.

Introduction. Recent trials demonstrated clinically significant benefits in HER2-nonamplified breast cancer with HER2-low expression using novel anti-HER2 antibody-drug conjugates. Thus, HER2-low breast cancer was proposed as a separate diagnostic entity. Herein, we reclassify HER2-negative cancers according to the new HER2-low category using a modified system and further investigate HER2-very-low expression. Methods. 114 HER2 immunohistochemistry (IHC)-negative invasive breast tumors were identified from the pathology database of Mayo Clinic, Jacksonville, FL, between January 2019 and August 2022. Two blinded breast pathologists (BP) independently rescored HER2 IHC slides at 200x and 400x magnification. Discordant cases between the two BPs were rescored together. The most recent 2018 ASCO/CAP HER2 scoring criteria were used. HER2 (0) was subdivided into HER2 (absent) and HER2 (very low). HER2 FISH testing was performed in all cases. Results. The cohort comprised of 38 (33.3%) HER2 (0) and 76 (66.7%) HER2 (1+) tumors. The first round of rescoring at 200x and 400x magnification resulted in 17 (14.9%) HER2 (absent), 31 (27.2%) HER2 (very low), and 64 (56.2%) HER2 (1+) and 2 (1.8%) HER2 (2+) tumors by BP1 and 20 (17.5%) HER2 (absent), 33 (28.9%) HER2 (very low), and 61 (53.5%) HER2 (1+) tumors by BP2. The combined final rescoring by BP1 and BP2 was as follows: 15 (13.2%) HER2 (absent), 35 (30.7%) HER2 (very low), 63 (55.3%) HER2 (1+), and 1 (0.9%) HER2 (2+) cases. A comparison of the first round of rescoring between two BPs showed substantial agreement with Cohen’s kappa value of 0.67. Both comparisons of first rescoring by BP1 and by BP2 to combined final rescoring showed almost perfect agreement with Cohen’s kappa value of 0.83.Follow-up FISH studies showed one amplified tumor. Conclusion. Our data support the need for finer granularity, classification, and understanding of HER2-low breast cancers. We also show that reproducibility between trained BP can be obtained, albeit with scoring at high power and low threshold for showing challenging interpretations.