Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The likelihood of a patient achieving pathological complete response (pCR) within the I-SPY2 trial of neoadjuvant therapy for locally advanced breast cancer is not significantly associated with race, shows research presented at the 2021 San Antonio Breast Cancer Symposium in Texas, USA.
“This indicates that women with high-risk breast cancer are equally likely to experience a survival benefit from receiving targeted neoadjuvant chemotherapy”, reported Beverly Kyalwazi, from the University of Chicago in Illinois, USA.
However, the investigators did identify a racial disparity in the outcomes of women with hormone receptor (HR)-positive, HER2-negative disease who did not achieve pCR, finding that in this subgroup Black women were almost twice as likely to experience recurrence than their White counterparts.
Beverly Kyalwazi explained that the adaptive study includes women attending 26 US institutions with stage II–III disease at high risk of early recurrence and compares standard neoadjuvant paclitaxel plus anthracycline chemotherapy alone or alongside an investigational agent.
This gives the I-SPY2 trial “the opportunity to investigate whether racial disparities in breast cancer persist in the face of subtype-specific treatment for high-risk breast cancer”, she said.
The current analysis included 974 patients, aged a median of 49 years, who were followed up for a median of 4.4 years after receiving one of the first 10 investigational agents, such as veliparib plus carboplatin, pertuzumab alone or with T-DM1, and pembrolizumab.
Of these patients, 81% self-identified as White, 12% as Black or African American and 7% as Asian; these groups of patients were comparable in terms of the distributions of Scarff-Bloom-Richardson grade, residual cancer burden class, and basal, HER2 or luminal molecular subtypes.
The primary endpoint of pCR was a comparable 32% for White patients, 30% for Black/African–American patients and 32% for Asian patients, the presenter said.
Similarly, the second endpoint of overall event-free survival (EFS) did not significantly differ between the three groups, and this was also true when assessing EFS only among patients who achieved pCR.
By contrast, analysis of women without a pCR showed that Black or African–American women were a significant 1.61 times more likely to experience recurrence than White women, and Asian women had a trend towards increased risk compared with White women but this did not reach significance.
And when the researchers assessed EFS in women without pCR by receptor subtypes, there was a significant 1.95-fold higher risk of recurrence for Black or African–American versus White patients with HR-positive, HER2-negative disease and a nonsignificant 1.47 increased risk for Asian patients.
No significant disparity was detected among patients without pCR with triple-negative, HR-positive, HER2-positive, or HR-negative, HER2-positive disease, although Beverly Kyalwazi remarked that these subgroup analyses had reduced power to detect any differences because of the smaller numbers of patients.
The investigators also examined 28 immune-related expression signatures associated with response to immune checkpoint inhibitor targets, such as PD-1 and PD-L1. These included 16 signatures associated with specific immune cell populations, such as T cells, B cells and dendritic cells, and seven immune-related signalling signatures, such as interferon (IFN) gamma.
Focusing on women with HR-positive, HER2-negative disease, they found that the IFN module signature had significantly higher expression in Black or African–American patients than in White patients. In addition, the ER/PR module expression was significantly higher in Asian than Black or African–American patients, while the opposite was true for the mitotic score signature.
“We hope that further evaluation into the tumour microenvironment will help us figure out the prognostic role of these differences”, said Beverly Kyalwazi.
Kyalwazi B, Yau C, Olopade O, et al. Analysis of clinical outcomes and expression-based immune signatures by race in the I-SPY2 trial. Abstract GS4-02; 2021 San Antonio Breast Cancer Symposium; Texas, USA: 7–10 December.
medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare. © 2021 Springer Healthcare part of the Springer Nature group