MammaPrint and BluePrint molecular profiles and clinical-pathological features of Asian early-stage breast cancer patients: a meta-analysis of six prospective clinical trials

Abstract

Background/Objective: Breast cancer incidence in Asian patients has increased in recent years; however, substantial variation in occurrence among Asian subpopulations has been reported. Furthermore, few studies have characterized clinical-pathological features and molecular subtypes in these patients groups. Here, we report a meta-analysis of clinical factors, pathology, molecular profiles, and treatment of Asian breast cancer patients enrolled in prospective registry trials from the United States and Hong Kong. Methods: This analysis includes Asian patients with early-stage, invasive breast cancer (n=172) for whom clinical characteristics were captured with informed consent, enrolled between 2011 and 2019 in the US (n=130) and Hong Kong (n=42). Patients were selected based on selfreported Asian ethnicity from 6 independent prospective clinical registry trials (Table), 1 of which, the US-based FLEX registry, is currently open to accrual. Clinical characteristics, pathology, and results from the 70-gene (70-GS, MammaPrint) risk of recurrence and 80-gene (80-GS, BluePrint) molecular subtyping signatures are reported. Treatment regimens and responses are reported for a subset of patients. Results: The majority of patients for whom subpopulation data were available (n=98) were Chinese (70.4%; n=27 enrolled in the US, n=42 enrolled in Hong Kong). Overall, the median age at diagnosis was 51 years, and 52.2% of patients were post-menopausal. Tumors were predominantly ductal carcinoma, not otherwise specified (NOS) (86.0%), T1 (58.3%), intermediate grade (46.5%), estrogen receptor-positive (ER+) (91.2%), and node-negative (74.3%). Frequency of lobular carcinoma was only 7.0%. Of patients with available family history (n=68), 54.4% report having at least 1 first- or second-degree family member with a history of cancer. By 70-GS and 80-GS (n=164) classification, tumors were 43.3% Luminal A, 41.5% Luminal B, 8.5% HER2-type, and 6.7% Basal-type. 56.3% of tumors (n=167) classified as 70-GS High Risk. The overall rate of pathological complete response (pCR, defined as absence of invasive carcinoma in both the breast and axilla) for patients with available neoadjuvant treatment and response data (n=24) was 45.8% (n=2 Basal-type, 6 HER2-type, 3 Luminal B). The majority (51.6%) of patients with available surgical data (n=91) received lumpectomy or segmental resection. Of the reported patients who received adjuvant chemotherapy (n=39), 87.2% were 70-GS High Risk. Conclusions: Although the sample size is small, the current analysis suggests younger age at diagnosis, reduced frequency of lobular carcinoma, and a greater proportion of High Risk and Luminal B tumors among Asian breast cancer patients, compared with published data on Caucasian breast cancer patients. Additionally, although neoadjuvant therapy response data were only available in a small number of patients, a high pCR rate indicates a need for additional investigation in these patient populations. Further studies, especially those that include genomic profiling, are needed to better understand racial and ethnic disparities and their impact on disease incidence, progression, and response to therapies.