MammaPrint May Predict Neoadjuvant Chemo Response in HR+, HER2- Early Breast Cancer

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Neoadjuvant chemotherapy leads to low pathologic complete response rate (pCR; ypT0/is ypN0) in patients with hormone receptor (HR) positive, HER2-negative early-stage breast cancer (ESBC), but MammaPrint and BluePrint,genomic tests that detect the activity of genes in patients with early-stage breast cancer, have potential to predict chemotherapy responses in specific breast cancer types compared to other receptor statuses, according to findings presented at the 2023 San Antonio Breast Cancer Symposium.¹

The MammaPrint test classifies patients with breast cancer into high and low risk of cancer recurrence, as genomic signatures have potential to predict chemosensitivity and advanced treatment compared to standard clinical subtypes. In past trials, MammaPrint-determined high-risk subtypes tended to have higher pCR rates when using specific treatments.

“The real-world date demonstrates (that) MammaPrint and BluePrint (have) clinical utility to predict the likelihood of achieving pCR after NCT in HR+ HER2-ESBC,” the researches stated in their poster presentation.

FLEX is a trial consisting of 12,328 patients, all with ESBC, who were tested by MammaPrint with or without BluePrint. This study focuses on MammaPrint’s High 1 (H1) and High 2 (H2) statuses as biomarkers for neoadjuvant chemosensitivity within the patient population (patients with HR-positive, HER2-negative ESBC) who had been enrolled in the FLEX study (n=214).

Within the study, MammaPrint identified two subtypes, H1 (n=142) and H2 (n=72), in patients with early-stage breast cancer. Characteristics such as age, menopausal status, race, tumor stage and lymph node status were also analyzed.

MammaPrint, H1, H2, BluePrint and pCR were adjusted and analyzed through age, race, grade, T stage, N stage and NCT regimen, according to findings from the study.

Fifty-nine percent of grade 3 tumors were categorized in the H2 tumor subgroup, while 98% of H1 tumors were Luminal B. Within the Luminal B (a type of breast cancer that responds to the hormone estrogen, while also having the HER2 gene) subgroup, only 51% were H2 tumors and 49% were basal-type (an aggressive molecular subtype of breast cancer), according to BluePrint.

The H2 tumor subgroup had a higher pCR rate, at 29.2%, in comparison to H1 tumors, at 6.3% (p<0.01). Among the 35 patients within the basal-type H2 subgroup the pCR rate was 37.1% (p<0.001).

“Although both MP High Risk groups exhibit chemosensitivity, High 2 tumors have higher chemosensitivity than High 1 tumors. Future studies will evaluate the correlation between NCT regimens (TC vs AC-T) pCR, and whole transcriptome changes to understand the underlying biology of treatment response,” the researchers noted.

Within BluePrint Luminal B tumors, patients with MammaPrint H2 tumors had a higher pCR rate (21.6%) compared to MammaPrint H1 tumors (5.8%; p=0.03). MP H2 (OR=4.91, p=0.003) and BluePrint Basal-Type (OR=3.54, p=0.03) tumors were also associated with a chance of pCR.

“Response to neoadjuvant immunotherapy is currently being evaluated in patients with HR+ HER2-, stage II-III, MP High 2 breast cancer in the SWOG 2206 trial (NCT06058377) that is open to accrual,” the researchers said.

REFERENCE:

O'Shaughnessy J, Pusztai L, Graham C, etl al. MammaPrint index predicts neoadjuvant chemosensitivity in patients with HR+HER2- early-stage breast cancer in the real-world evidence FLEX study. Presented at: San Antonio Breast Cancer Conference; December 5-9, 2023; San Antonio, TX. Abstract: PO5-15-04.