How ER-positive, HER2-positive breast cancer tumors respond to a short course of hormonal treatment may help to determine whether more aggressive treatment options are necessary for each patient or not, according to translational findings published in eBioMedicine. Tumor subtype changes after 2 weeks of treatment with aromatase inhibitors may then help to determine prognosis and guide treatment decisions going forward.
“In this new study, we’ve shown that [breast cancer] subtypes can shift after just 2 weeks of hormone therapy,” stated corresponding study author Maggie Chon U. Cheang, MD, PhD, Leader, ICR-CTSU Integrative Genomic Analysis in Clinical Trials Team, The Institute of Cancer Research, London, United Kingdom. “This insight helps us identify which patients are likely to respond well and which may show early signs of treatment resistance, offering the opportunity to tailor treatment strategies sooner. Ultimately, our findings move us closer to more precise, patient-centered care for this overlooked breast cancer subtype.”
Background and Study Methods
The investigators analyzed tumor samples before and after treatment from 313 patients participating in the phase III POETIC trial. The trial explored the benefit of short-duration perioperative aromatase inhibition compared with standard adjuvant therapy alone in postmenopausal women with ER-positive, PR-positive invasive breast cancer.
Although the POETIC study did not find a clear benefit for 2 weeks of perioperative hormonal therapy for these patients, translational studies from the trial have been beneficial, including for the identification of the five breast cancer subtypes based on molecular and genetic characteristics of the tumor.
Here, the researchers looked to prognosticate which patients would respond better to de-escalated treatment. The study authors assessed how patients’ tumors and subtypes responded to the short-term treatment by looking at Ki67 levels and changes in gene-signature expressions.
Key Study Findings
A total of 79% of luminal B tumors at baseline shifted to luminal A subtypes after 2 weeks of treatment with aromatase inhibitors. Luminal A tumors were associated with a better time to recurrence compared with tumors that were still luminal B after treatment (hazard ratio [HR] = 0.2; 95% confidence interval [CI] = 0.06–0.72; P = .01).
Tumors that remained luminal A after treatment showed the lowest risk of relapse. The researchers suggested that these patients should continue with 5 years of hormonal therapy without the addition of more aggressive treatments.
For patients with luminal B tumors that did not shift with treatment, their disease was at least 1.5 times more likely to relapse. For these patients, the researchers recommended more intensive treatments with the addition of a CDK4/6 inhibitor.
“This research offers insight into how the biology of some breast cancers changes in response to hormone therapy. I look forward to seeing how these findings inform treatment decisions in the future—helping some patients avoid unnecessary side effects while ensuring that those with more aggressive tumors are offered alternative and more effective drugs,” stated Kristian Helin, PhD, MSc, Chief Executive Officer, The Institute of Cancer Research.
Disclosure: The study was funded by The Institute of Cancer Research. For full disclosures of the study authors, visit thelancet.com.
