ESMO Breast 2021: Distinct Gene Signatures Associated With Pathologic Complete Response
Posted: Friday, May 28, 2021
At the European Society for Medical Oncology (ESMO) Breast Cancer Virtual Congress 2021, Monika Graeser, PD Dr, of the Senologie, Westdeutsche Studiengruppe GmbH, Mönchengladbach, Germany, and colleagues presented their analysis on the associations of stromal tumor-infiltrating lymphocytes and biological signatures with pathologic complete response and survival in patients with HER2-positive/hormone receptor (HR)-negative breast cancer (Abstract LBA2). Ultimately, these researchers discovered “distinct gene signatures associated with pathological complete response versus invasive disease–free survival.”
“Immune response signatures can augment morphologic data from stromal tumor-infiltrating lymphocytes; the potential role of immune response in preventing recurrence suggests that patients with upregulated immune response signatures could be candidates for de-escalation concepts in HER2-positive breast cancer,” the investigators added.
The phase II WSG-ADAPT trial enrolled 134 patients with clinical stage 1 to 4, HER2-positive/HR-negative breast cancer with or without lymph node metastasis. Participants were randomly assigned to arm A (n = 92) or arm B (n = 42) to receive either pertuzumab plus trastuzumab alone or with paclitaxel added, respectively.
Favorable biomarkers for pathologic complete response included ERBB2 (odds ratios [OR] = 1.7) and estrogen receptor pathway signaling signatures (PR = 1.7), whereas the PTEN signature was an unfavorable indicator of pathologic complete response (OR = 0.6). Eleven invasive events occurred after 60 months median follow-up, but none were recorded after pathologic complete response.
In terms of invasive disease–free survival, multiple gene signatures related to estrogen receptor signaling and immune response were favorable markers, demonstrating a hazard ratio from 0.4 to 0.6. These patterns were more distinct in arm A, with an unfavorable BRCAness signature (hazard ratio = 2.0). Of note, stromal tumor-infiltrating lymphocytes did not display a significant correlation with pathologic complete response or invasive disease–free survival. However, those at baseline were positively associated with immune response signatures.
Disclosure: The study authors reported no conflicts of interest.
