HER2-negative Early-stage Breast Research Articles

Abstract PO2-02-03: Clinical and pathological factors associated with Oncotype DX® 21-Gene recurrence score in patients diagnosed with early stage breast cancer in a low-middle income country

Abstract INTRODUCTION: Oncotype DX® recurrence score (ODX RS) is a 21-gene assay warranted to determine the the prognosis in patients with hormone receptor positive, HER-2 negative early stage breast cancer. In this context, the test is also predictive of benefit of adjuvant chemotherapy.1,2,3 OBJECTIVES: We aimed to correlate the clinical and pathological factors associated with Oncotype DX® 21-Gene in patients diagnosed with early stage Breast Cancer. Additionally, description of adjuvant treatment patterns and survival outcomes were described according to the Oncotype DX® 21-Gene result. METHODS: Data from medical records from a single center in Brazil were collected retrospectively from women over 18 years diagnosed with early breast cancer between 2012 and 2022. Included patients were diagnosed with stage T1-T2 breast cancer, hormone receptor positive, HER-2 negative, with up to three positive lymph nodes. All included patients had an Oncotype DX® test performed after definitive breast surgery. The ODX RS has been categorized into two levels according to menopausal status. Correlation between breast cancer recurrence and clinicopathological characteristics was done. The software SPSS was used for statistical analyzes with the significance of 0.05. RESULTS: From 197 patients, 20 have had breast cancer recurrence (10.15%) whom 10 were premenopausal and 10 were postmenopausal. The median ODX RS in these 20 patients was 15 (ranged from 9 to 31). The most common site of recurrence was breast and regional recurrence in 18 patients (90%). Adjuvant chemotherapy was omitted in 16 patients (80%) who have had breast cancer recurrence. Among premenopausal patients whose ODX RS was >20, 33 patients (91.66%) received adjuvant chemotherapy. Among postmenopausal patients whose ODX RS was >25, 19 (86.36%) received adjuvant chemotherapy. The probability of recurrence free survival was worse in premenopausal patients > 44-years-old compared to those with < =44 years-old (p = 0.036) and also worse in histological grade 3 tumors compared to grade 1 (p=0.0048). Tumor size >14 millimeters (mm) was correlated to worse recurrence free survival in premenopausal patients (p=0.017). Low estrogen and progesterone receptor was associated with a higher ODX RS (p=0.0035 and p< 0.0001, respectively) in premenopausal patients, but not associated with recurrence free survival. Clinicopathological characteristics and recurrence free survival correlation in postmenopausal patients were not significant. CONCLUSION: This retrospective analysis suggests that factors other than the Oncotype DX® score, such as age and grade contributed to worse survival outcomes among our patients population. Of note, age older than 44 years-old, histological grade 3 and tumor size >14 mm were associated with a higher probability of recurrence in premenopausal patients, despite the Oncotype DX® score. REFERENCES: 1. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med [Internet]. 2004;351(27):2817–26. Available from: http://dx.doi.org/10.1056/NEJMoa041588. 2. Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med [Internet]. 2018;379(2):111–21. Available from: http://dx.doi.org/10.1056/NEJMoa1804710. 3. Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, et al. 21-gene assay to inform chemotherapy benefit in node-positive breast cancer. N Engl J Med [Internet]. 2021;385(25):2336–47. Available from: http://dx.doi.org/10.1056/NEJMoa2108873. Table 1 – Clinical and pathological characteristics of 197 hormone receptor positive, HER-2 negative early breast cancer patients who did the Oncotype DX® 21-Gene Recurrence Score assay. Data from medical records collected retrospectively of women diagnosed with early breast cancer between 2012 and 2022 from a single center in Brazil. Figure 1 – Probability of recurrence free survival in premenopausal patients according to age <=44 (blue line) or > 44-years-old (pink line). Data from medical records collected retrospectively of women with hormone receptor positive, HER-2 negative early breast cancer who did the Oncotype DX® 21-gene assay diagnosed between 2012 and 2022 from a single center in Brazil. Figure 2 – Probability of recurrence free survival in premenopausal patients according to histological grade. Tumor with histological grade 1 (blue line) or histological grade 3 (pink line). Data from medical records collected retrospectively of women with hormone receptor positive, HER-2 negative early breast cancer who did the Oncotype DX® 21-gene assay diagnosed between 2012 and 2022 from a single center in Brazil. Citation Format: Carolina Cavalcanti Gonçalves Ferreira, Julio Araujo, Shermann Brandão Rodrigues Moreira, Antônio Buzaid, Débora Gagliato. Clinical and pathological factors associated with Oncotype DX® 21-Gene recurrence score in patients diagnosed with early stage breast cancer in a low-middle income country [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 PO2-02-03.

Role of Oncotype-DX testing in older versus younger women with hormone receptor positive & Her-2 negative early stage breast cancer

Introduction: Oncotype DX Breast Recurrence Score (RS) has proven to be useful in predicting the risk of recurrence and the potential benefit of chemotherapy in hormone-receptor positive, HER-2 negative early-stage breast cancer patients. The aim of this study (part of service evaluation) was to explore the role of Oncotype DX recurrence scores in the treatment of older versus younger women, treated within the Hywel Dda Health-Board between 2010 to 2018.

Abstract PS6-34: Real life impact of TAILORx trial in a multi-center healthcare system: A comparison of management practice one year before and after the release of the trial

Abstract Introduction: Oncotype DX is a 21 gene assay which has been shown to be useful in predicting the risk of breast cancer recurrence. TAILORx trial compared survival with the use of hormonal therapy (HT) vs. chemo-hormonal therapy (CHT) in early-stage, Hormone receptor-positive, HER2-negative, axillary lymphnode-negative breast cancer who had an Oncotype DX recurrence score in the intermediate range (11-25), The study found HT to be non-inferior to CHT in that group, especially in women older than 50. Materials and methods: We studied 1084 patients with hormone receptor-positive, HER-2 negative early stage breast cancer at a multi-center setting in South Dakota and North Dakota who were diagnosed one year before and after the results of the TAILORx trial were presented. We aimed to identify any change in practice after the trial was published as compared to the year prior. Chi-square analysis was used to compare demographics of patients and management practices before and after the TAILORx trial publication. Results: We did not find any statistically significant change in Oncotype DX testing frequency across various age groups, tumor sizes, tumor grades or amongst patients who had lymphnode negative or one axillary lymph node positive disease (Table-1).We also did not find any statistically significant difference in management of early stage breast cancer patients (Table-2) that matched our inclusion criteria and had an intermediate risk Oncotype Dx score of 11-25(n=266). Conclusion: Our results indicate that management of early stage breast cancer at our center was not significantly impacted by the results of TAILORx. Rare use of CHT prior to TAILORx reporting suggests that practice prior to this trial was largely based on earlier trials suggesting minimal benefit for CHT in the intermediate risk group. Larger studies may be able to identify smaller changes in practice resulting from this study and should be pursued. Table-1: Frequency of Oncotype Dx testing one year before and after the TAILORx trial was released overall and in various sub-categories based on age of the patient, tumor size and tumor grade. Last row indicates the frequency comparison in patients who had one axillary lymph node positive status.Before TAILORx (N=512)After TAILORx (N=572)p-valuen (%)n (%)Overall204 (40)234 (41)0.7212Age< 5044 (46)31 (37)0.225450 - 69121 (46)146 (49)0.4519Equal or > 7039 (26)57 (30)0.3986Tumor Size< 1 cm41 (25)50 (28)0.53881 - 1.9 cm97 (51)122 (53)0.60552 - 2.9 cm40 (44)44 (42)0.77283+ cm24 (39)18 (32)0.4161Tumor Grade156 (39)63 (42)0.62002113 (48)135 (47)0.8542334 (26)35 (27)0.9768LN Positive31 (33)36 (32)0.9403 Table-2: Comparison of treatment received by patients in the intermediate risk group (score:11-25) based on Oncotype Dx test before and after the release of TAILORx trial , Chi sq p-value=0.5635, HT (Hormonal Therapy), CT (Chemotherapy).Before TAILORxAfter TAILORxHT + CTn=15n=135.91%5.12%HT Alonen=108n=11842.52%46.46% Citation Format: Mahum Shahid, Moataz Ellithi, Mohamed Abdallah, Arsalan Arshad, Mansi Oberoi, Mckenna L Eisenbeisz, Christopher M VanHove, Ty A Moody, Isaak N Ailts, Andrew J Foley, Morgan Nelson, Jonathan Bleeker. Real life impact of TAILORx trial in a multi-center healthcare system: A comparison of management practice one year before and after the release of the 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 PS6-34.

Abstract P6-09-31: Study of oncotype DX® recurrent score in bilateral synchronous primary invasive breast cancer

Abstract Background: The 21-gene Oncotype Dx® Recurrence Score (RS) is routinely used to assess the risk of distant recurrence and benefit for adding chemotherapy in the treatment of ER positive HER2 negative early stage breast cancer. Among patients diagnosed with bilateral primary breast cancer there is limited information on the utilization of RS for each primary cancer. In this study, we evaluate the concordance of RS in bilateral breast cancer, and the value of testing both primary cancers in patients diagnosed with synchronous bilateral breast cancer Materials & Methods: This is an IRB approved retrospective study. From 2007 to present, we identified 158 patients with synchronous (within 6 months) bilateral primary breast cancer in our Institutional databases. In this dataset, there were 36 patients who had early stage ER positive, and Her-2 negative bilateral invasive cancer, and for whom the 21-gene Oncotype Dx® RS test was ordered. We excluded patients with bilateral invasive cancer who did not have Oncotype Dx® RS test performed (n=20), patients with bilateral in-situ cancers (n=15), patients with unilateral invasive with contralateral in-situ cancer (n= 64), and patients with locally advanced stage of one or both primary invasive cancers (n=23). In this study, RS score was scored low risk < 18, intermediate 18-30, and high risk >31. The RS for bilateral primary cancers was noted as concordant if the 2 values were in the same risk category and discordant when 2 values represented different risk category. Results: Among the 36 patients, 19 patients had Oncotype Dx® RS tested for one primary cancer, and 17 patients had testing from bilateral primary cancers. Patients median age is 55 years (range: 44 years to 75 years), and invasive duct cell was the most common histology. The RS distribution of low risk, intermediate risk and high risk was 60 %, 30% and 10%, respectively. Further, evaluation of the 17 patients in whom the RS score from bilateral invasive breast cancers was obtained, we noted that the RS was concordant in 11 patients (64.7%), and discordant in 6 patients (35.3%). In 4/6 patients the discordance was between low and intermediate risk, and in 2/6 patients it was between low and high risk. Clinical variables including age, histology, receptor positivity, and grade were not predictive of the rate of RS concordance between the 2 primary cancers. Conclusion: The significant rate of discordance observed in our study suggests that the 21-gene RS for each invasive primary breast cancer should be routinely obtained in patients presenting with bilateral breast cancers. Albeit synchronous events, the individual risk assessment of each primary cancer would help guide risk-tailored personalized cancer treatment. Citation Format: Chadha J, Goel A, Wallach J, Shao T, Klein P, Malamud S. Study of oncotype DX® recurrent score in bilateral synchronous primary invasive breast cancer [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 P6-09-31.