Disparities in Survival Outcomes Revealed With BluePrint and MammaPrint Subtyping in HR+/HER2– Breast Cancer

Sonya Reid, MD, MPH

Precise stratification of hormone receptor (HR)–positive, HER2-negative breast cancer using BluePrint (BP) and MammaPrint (MP) assays revealed comparable 3-year recurrence-free survival (RFS) rates between Black and White patients despite observed racial differences in the distribution of molecular subtypes, according to data presented during the 2023 San Antonio Breast Cancer Symposium.¹

Findings from a comparative study showed that Black women experienced a higher frequency of high-risk, Basal-Type tumors (P = .004) and Luminal B–Type tumors (P = .001) compared with White women. In Black women, 10.7%, and 48.9% of tumors were Basal-Type and Luminal B–Type, respectively; these percentages were 6.0% and 39.3% in White women. Notably, low-risk, Luminal A–type disease (P < .001) was more commonly observed in White women vs Black women.

Black patients experienced a 3-year RFS rate of 93.6% (95% CI, 90.7%-96.7%), vs 93.6% (95% CI, 91.1%-96.3%) in White patients. Further stratification of 3-year RFS by MP and BP assays showed that White patients with Luminal A–, Luminal B–, and Basal-Type breast cancer experienced 3-year RFS rates of 97.0% (95% CI, 94.7%-99.4%), 90.6% (95% CI, 85.7%-95.8%) and 80.6% (95% CI, 65.2%-99.7%), respectively (P = .004). Conversely, Black patients experienced 3-year RFS rates of 96.7% (95% CI, 93.1%-100%), 92.5% (95% CI, 87.9%-97.3%) and 88.9% (95% CI, 79.1%-99.8%) in these respective disease types.

“MP and BP more precisely stratified tumors, resulting in distinct 3- and 10-year outcomes independent of race and beyond clinical subtype alone,” lead study author Sonya Reid, MD, MPH, who is an assistant professor in the Division of Hematology/Oncology at Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues, stated in a poster presentation of the data. “We identified racial differences in the distribution of MP and BP subtypes, but within each subtype, survival outcomes at 3 years were comparable between Black and White patients.”

This comparative analysis was conducted utilizing the 80-gene BP assay alongside MP, which is a 70-gene assay assessing the risk of distant recurrence. Both molecular subtyping assays are known to have prognostic value for patient outcomes on therapy.

MP was previously shown to aid treatment decision making in the phase 3 EORTC 10041/BIG 3-04 MINDACT (NCT00433589) trial by accurately identifying patients with clinically high-risk, genomically low-risk tumors who are likely to experience substantial benefit from regimens not including chemotherapy.² Additionally, prior use of BP revealed that HR-positive tumors designated as Basal Type exhibit heightened aggressiveness and tend to be higher grade.³

Although Black women are 41% more likely to die from breast cancer than White women, they remain underrepresented in clinical trials and population studies.¹ To assess how the heightened prevalence of HR-positive/Basal-Type tumors contributes to disparities in long-term survival within this group, investigators conducted a comparative analysis of 3-year outcomes and distribution in Black and White women diagnosed with HR-positive, HER2-negative breast cancer. The correlation between MP and BP and their impact on 10-year outcomes within a subset of Black women was also evaluated.

The study included adult patients with stage I to III HR-positive, HER2-negative breast cancer enrolled onto the population-based BEST study (R01-CA204819) between 2005 and 2015, as well as patients enrolled in the ongoing observational FLEX study (NCT03053193). A total of 139 Black patients from the BEST study and 429 patients from the FLEX study were included; these patients were matched with White patients enrolled in FLEX (n = 568), controlling for age, tumor size, and nodal status.

Patients were categorized as either low risk or high risk according to MP analysis, and subsequently sub-classified as having Luminal A–Type, Luminal B–Type, HER2-Type or Basal-Type disease with BP.

The primary end point of the study was 3- and 10-year RFS. Secondary end points included 10-year overall survival (OS). Differences in RFS and OS were evaluated using Kaplan-Meier analyses and log-rank test. The median follow-up was 3.0 years for patients in the FLEX study and 10.1 years for patients in the BEST study.

Within the total population (n = 1136), 38.1% of patients were pre- or peri-menopausal (41.9% of Black women; 34.1% of White women), and 72.5% of patients were lymph node–negative (72.5%; 72.5%). Most patients had intermediate-grade disease (46.4%; 57.0%), followed by low-grade (24.4%; 26.8%) and high-grade (29.2%; 16.2%) breast cancer. T1 tumor size was observed in 58.4% of the total population (57.7%; 59.1%), followed by T2 (34.4%; 34.9%) and T3 to T4 (7.9%; 6.0%) disease.

An additional analysis of long-term survival outcomes from the BEST study showed that Black patients experienced a 10-year RFS rate of 88.4% (95% CI, 82.9%-94.2%) and a 10-year OS rate of 89.0% (95% CI, 82.7%-94.7%). Further stratification revealed that Black patients with Luminal A–Type tumors (n = 44) had the highest 10-year RFS and OS rates vs other tumor subtypes, at 97.7% (95% CI, 93.4%-100%; P = .080) and 100% (P = 0.026), respectively. Those with Luminal B–Type breast cancer (n = 71) had a 10-year RFS rate of 83.5% (95% CI, 74.8%-93.1%) and a 10-year OS rate of 83.5% (95% CI, 74.8%-93.1%). Ten-year RFS and OS rates were both 85.0% for Black patients with Basal-Type tumors (95% CI, 70.7%-100%), indicating that diverse patients may experience more equivalent outcomes when classified using these molecular subtyping assays in tandem, and that patients with low-risk, Luminal A–type disease should potentially avoid overtreatment, regardless of race.

“More aggressive treatment can improve outcomes for [patients with HR-positive, Basal-Type tumors], as demonstrated by improved OS in [those who] achieved pathologic complete response,” investigators stated in the poster. “These data highlight the importance of genomic testing to help optimize treatment and reduce outcome disparities in Black women,” they concluded.

References

1. Reid S, Shu X-O, Venton L, et al. MammaPrint and BluePrint identify racial disparities among women with HR+HER2- early-stage breast cancer. Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; abstract PO1-28-01.
2. Cardoso F, van't Veer LJ, Bogaerts J, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729. doi:10.1056/NEJMoa1602253
3. Reid SA, Pal T, Shu X-O, et al. Whole transcriptomic analysis of HR+ breast cancer in Black women classified as basal-type by BluePrint. J Clin Oncol. 2022;40(suppl 16):517. doi:10.1200/JCO.2022.40.16_suppl.517