Abstract PS6-41: Mammaprint and blueprint as prognostic indicators for elderly patients with early stage breast cancer
Authors: Peter W. Blumencranz, Mehran Habibi, Lisa Blumencranz, Andrea Menicucci, Shiyu Wang, Amy Truitt, William Audeh, Jolanta L. Baginski, Steven Shivers, Geza Acs, Charles E. Cox
Journal: Cancer Research (2021)

Abstract Background: Elderly breast cancer (BC) patients are an understudied population, with limited evidence regarding treatment options and outcomes and a lack of research involving prognostic multigene assays for this group. One study in patients 65-89 years old with an Oncotype DX Recurrence Score ≥ 26 concluded that gene expression profiling tests have limited utility in elderly patients, and should only be used for patients aged 65-74 with no/low to moderate comorbidities and not for patients ≥ 75. In this study, the 70-gene risk of distant recurrence signature, MammaPrint (MP), and 80-gene molecular subtyping signature, BluePrint (BP), were evaluated in both the neoadjuvant and adjuvant settings in elderly patients with early stage BC. Methods: This analysis included 211 BC patients classified as cT2-4N0-3M0 (T2 &amp;gt; 3.5 cm if N0) who received neoadjuvant chemotherapy and enrolled in the Multi-Institutional Neoadjuvant Therapy MammaPrint Project (MINT) study from 2011-2016. Lymph node (LN) involvement was established following neoadjuvant treatment. The second analysis included 517 early stage BC patients with 0-3 positive LNs who enrolled in the community based cohort study (COPPER) from 2009-2016. Patients were given adjuvant treatment following standard of care. Patients from both cohorts were divided into age at diagnosis groups: &amp;lt; 65, 65-74, and &amp;gt; 74. MP stratified patients into either Low Risk (LR) or High Risk (HR) groups. BP classified patient samples into Luminal, HER2, or Basal subtype. Kaplan Meier analysis and log-rank test were used to assess differences in overall survival (OS) and distant metastasis free survival (DMFS). Clinical risk assessment based on the MINDACT trial algorithm was performed. Results: From MINT, 35 patients were ≥ 65 years old; 80% were HR and 20% were LR. Pathological complete response (pCR) was achieved in 36% (10/28) of elderly HR patients, of whom 70% were HER2 and 30% were Basal by BP. Nodal downstaging occurred in 55% (11/20) of LN positive elderly HR patients, of whom 64% (7/11) achieved pCR. BP classified patients with nodal downstaging as HER2 (55%), Basal (36%), or Luminal (9%). Importantly, pCR and nodal downstaging were more likely to be achieved in HR tumors and correlated with BP subtype in both young and elderly patients. From the COPPER cohort, 77% of HR patients 65-74 years old received chemotherapy (CT), whereas 74% of LR patients omitted CT. Of patients &amp;gt; 74, 49% of HR patients received CT, whereas 75% of LR patients omitted CT. OS and DMFS probabilities indicated good survival outcomes in LR patients that omitted CT and HR patients that received CT, with no significant difference between age groups. A majority of HR patients treated with CT and over 1/3 of LR patients that omitted CT had high clinical risk. Interestingly, among all patients that had a metastasis event, mortality was less likely to occur in patients that received dose dense AC (doxorubicin and cyclophosphamide). Conclusion: MP and BP may identify HR elderly patients who are likely to achieve nodal downstaging and pCR. Elderly patients were safely spared or assigned adjuvant CT based on MP results independent of clinical risk. Furthermore, these data are in line with previous studies that suggest similar survival benefits between older and younger patients who are candidates for aggressive CT regimens. MP and BP elucidate information about tumor biology and provide prognostic value, which may help inform treatment decisions, independent of patient age. MINTAge group&amp;lt; 6565-74&amp;gt; 74MP resultHRLRHRLRHR# of patients152242177% of patients with pCR35% (53/152)033% (7/21)043% (3/7)# of LN+ patients103181456% of LN+ patients with nodal downstaging49.5% (51/103)22% (4/18)50% (7/14)067% (4/6)% of LN+ patients with pCR &amp; nodal downstaging65% (33/51)071%(5/7)050%(2/4)COPPERAge group&amp;lt; 6565-74&amp;gt; 74MP resultHRLRHRLRHRLR# of patients1409988665569# of patients received CT121256813278# of patients omitted CT116717492052# of patients with unknown treatment873489Groups treated based on MPHR treated with CTLR omitted CTAge group&amp;lt; 6565-74&amp;gt; 74&amp;lt; 6565-74&amp;gt; 745-yr DMFS probability (95% CI)91% (80.2-96.7)87% (60.2-91.4)87% (55.2-96.6)100%98% (84.3-99.7)94% (75.9-98.5)5-yr OS probability (95% CI)94% (80.2-98.2)96% (83.4-98.9)86% (54.7-96.5)100%98% (84.3-99.7)97% (80.4-99.6)% Clinical high risk83% (100/121)76% (52/68)63% (17/27)34% (23/67)37% (18/49)35% (18/52) Citation Format: Peter W. Blumencranz, Mehran Habibi, Lisa Blumencranz, Andrea Menicucci, Shiyu Wang, Amy Truitt, William Audeh, Jolanta L. Baginski, Steven Shivers, Geza Acs, Charles E. Cox, MINT Investigators Group. Mammaprint and blueprint as prognostic indicators for elderly patients with early stage breast cancer [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 PS6-41.