Abstract P4-02-20: Utility of the 70-gene signature and 10 year follow up in patients with early-stage breast cancer in a single institution study
Authors: Nasrazadani Azadeh , Marti Juan L. Gomez , Rosenzweig Margaret Q. , McGuire Meghan , Quinn Katie , Haan Josien , Houzelle Alexandre , Bhargava Rohit , Audeh William , Brufsky Adam M. 
Published: March 2023

Introduction: Genomic tests are routinely used by clinicians to guide treatment decisions in early-stage breast cancer (EBC). The 70-gene MammaPrint assay (MP) assesses the risk of distant recurrence in untreated patients with EBC and categorizes the tumors as High Risk (HR, MP index: -1 to ≤0) or Low Risk (LR, &gt;0 to +1). The LR category is further divided into Low but non-UltraLow (LNUL; &gt;0 to ≤0.355) and UltraLow Risk (UL; &gt;0.355 to 1). Here, we report the risk of distant recurrence by MP and 10-year outcomes in patients with EBC diagnosed at Magee Women’s Hospital of the University of Pittsburgh Medical Center.

Methods: In this retrospective analysis, 259 women diagnosed with EBC between 2005 and 2008, who received a MP result, were included. Patient clinical and tumor characteristics were collected. The median FU was 13.1 year among patients with clinical data. Treatment received, 10-year Distant Metastasis Free Interval (DMFI) and 10-year Breast Cancer Specific Survival (BCSS) are reported according to the MP groups. Differences in DMFI and BCSS between MP risk groups were assessed by log-rank. Patients were treated at the physician’s discretion. Treatment was started prior to obtaining MammaPrint results.

Results: Among the 259 patients, 69% were post-menopausal women (mean [range] age: 58 [31-81] years) and diagnosed with hormone receptor-positive HER2-negative tumors (90%), grade 1 or 2 (64%), and without lymph node invasion (93%). In this cohort, 69% (n = 159) had a MP LR result and 31% (n = 100) had a MP HR result. Overall, 14% (n = 35) of patients had a MP UL risk of recurrence of whom 74% (n = 26/35) were post-menopausal women. Substantially more patients received chemotherapy in the HR group (57%, n = 57) compared with the LR group (15%, n = 24) (table). Considering that treatment was initiated before MammaPrint results were known, MP results might have allowed chemotherapy de-escalation in in 15% (n = 24) of patients with a MP LR. Similarly, in the 39% (n = 39) of women with a MP HR treated with endocrine therapy only, knowledge of MP results could have provided important information to add chemotherapy to the treatment plan.. In the MP UL group, 74 % (n = 26) of patients were treated with endocrine therapy only compared with those who received chemotherapy (9%, n = 3) and no adjuvant treatment (9%, n = 3). The 10-year DMFI and 10-year BCSS were higher in the LR compared with the HR group (table). When further stratifying the MP LR group in LNUL and UL, the 10y DMFI was 0.97 (95% CI; 0.94 – 1.00) and 1.00 for the MP LNUL and UL groups, respectively. Within the first 10 years, 8 of the 10 distant recurrences observed were in the MP HR group, and 2 were in the MP LNUL group. Among the 18 recorded deaths, 5 were breast cancer-related, 4 in the MP HR and 1 in the MP LR (LNUL) groups.

Discussion: In this single-institution retrospective analysis, all patients showed excellent BCSS and DMFI outcomes confirming the ability of MP to correctly predict the good prognosis (LR) and poor prognosis (HR) in patients with EBC. In this analysis, as observed in other cohorts, women with a MP UL risk result had an excellent prognosis at 10 years while being treated mostly with endocrine therapy only. Taken together, with the low endocrine therapy adherence reported in the literature, these data suggest that patients with a MP UL result may be candidates for further treatment de-escalation to optimize the risk/benefit ratio of endocrine therapy in future studies.

Table 1. Clinical outcomes and treatment received in patients stratified by MammaPrint results * Patients were treated at the physician’s discretion a p = 0.011, MP LR vs MP HR. b p = 0.032, MP UL vs LNUL vs HR. c p = 0.061 MP LR vs MP HR. d p = 0.170, MP UL vs LNUL vs HR.

Citation Format: Azadeh Nasrazadani, Juan L. Gomez Marti, Margaret Q. Rosenzweig, Meghan McGuire, Katie Quinn, Josien Haan, Alexandre Houzelle, Rohit Bhargava, William Audeh, Adam M. Brufsky. Utility of the 70-gene signature and 10 year follow up in patients with early-stage breast cancer in a single institution study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-20.