What Factors Can Predict Response to HER2-Directed Neoadjuvant Therapy?

Several clinicopathologic features of HER2-positive breast cancer patients were found to be associated with response to neoadjuvant therapy in a new study. These factors could be used to predict response to, and subsequently guide, treatment.

“We have much to learn regarding the potential biological and patient-specific predictors of pathologic complete response,” wrote study authors led by Jane L. Meisel, MD, of the Winship Cancer Institute at Emory University in Atlanta. “A better understanding of these may lead to an improved ability to choose a neoadjuvant regimen for individual patients.”

The researchers conducted an analysis of 173 patients with HER2-positive breast cancer diagnosed between 2010 and 2016 at a single institution who were treated with HER2-targeted neoadjuvant therapy. 

The results were published online ahead of print on September 18 in Clinical Breast Cancer.

The scientists examined the correlations between a variety of clinicopathologic features and pathologic complete response (pCR), which has been shown to be a strong predictor of disease-free survival. 

The mean age in the study was 53.9 years, and the mean tumor size was 3.6 cm. Most of the cohort had a HER2 immunohistochemistry level of 3+ (76.8%), while 23.2% had 1+ or 2+ disease. A total of 85 patients were estrogen receptor-positive (49.1%), and 82 patients were progesterone receptor-positive (47.4%), according to the data.

All patients received trastuzumab, and 56% also received pertuzumab. The most common chemotherapy agents included docetaxel and carboplatin. A total of 110 patients (63.6%) had a residual cancer burden score of 0 or I, indicating a response to neoadjuvant therapy; 87 of those patients had a score of 0, which was considered a pCR, the authors wrote. 

Several factors were found to be associated with the likelihood of pCR on a multivariate analysis. HER2-IHC of 3+ was strongly associated with pCR, with an odds ratio of 8.44 (95% CI, 2.87-24.85; P< 0.001). Tumor size, ER and PR expression, and Ki67 levels were also significantly associated with pCR, the investigators added. 

“In HER2-positive breast cancers, low ER and PR expression, higher Ki67 index, and high HER2 gene amplification and protein expression were associated with an increased response to neoadjuvant HER2-targeted chemotherapy,” the authors concluded. “These biomarkers may be useful for selecting and individualizing patient treatments. Our results also demonstrate HER2 IHC to be a strong predictor of response to upfront therapy.”

 They added that larger studies would be helpful to confirm these conclusions. 

“More research is needed to understand the role of immune-based biomarkers in responsiveness to neoadjuvant HER2-directed therapy,” they wrote.

References:

Meisel J, Zhao J, Suo A, et al. Clinicopathologic factors associated with response to neoadjuvant anti-HER2-directed chemotherapy in HER2-positive breast cancer. Clin Breast Cancer. 2019. DOI: https://doi.org/10.1016/j.clbc.2019.09.003