Axillary Nodal Response to Neoadjuvant T-DM1 Combined with Pertuzumab in a Prospective Phase II Multi-Institution Clinical Trial

by Selleckchem | Jan 29 2024

Background: Patients with ERBB2(HER2)-positive breast cancer experience high pathologic complete response (pCR) rates after standard neoadjuvant anti-HER2 systemic therapy. We examined axillary pathologic nodal response to neoadjuvant dual HER2-targeted therapy alone, based on breast pathologic response, in a multi-institution clinical trial.

Study design: Patients with HER2-positive breast cancer were enrolled to a phase II single-arm trial which administered 6 cycles of neoadjuvant trastuzumab emtansine (T-DM1) plus pertuzumab. Rates of pathologic nodal disease (ypN) in patients who were clinically node-negative (cN0) and node-positive (cN1) were analyzed, by residual breast disease (pCR and residual cancer burden [RCB] I-III).

Results: 158 patients completed pre-operative treatment and proceeded to surgery. Of 92 patients who were cN0, 48 (52.2%) and 10 (10.9%) experienced breast pCR and RCB I, respectively. Of these, 100% were ypN0. Of 34 with RCB II-III, 26 (76.5%) were ypN0. Of 30 patients who were cN1 with breast pCR, 100.0% were ypN0; 66.7% of the 12 cN1 with RCB I were ypN0 and 25.0% of the 24 cN1 with RCB II-III were ypN0. ypN0 rates were significantly different between patients who did and did not experience a pCR, in both cN0 (P=0.002) and cN1 subgroups (P<0.001).

Conclusions: Patients with HER2-positive breast cancer treated with dual HER2-targeted therapy who experienced a breast pCR or RCB I response were frequently ypN0. These findings support future trials considering omission of axillary surgical staging for patients with HER2positive breast cancer in neoadjuvant trials of active HER2-targeted regimens, particularly if they experience breast pCR or RCB I.

Comments:

This study explores the relationship between breast and axillary response in HER2-positive breast cancer patients undergoing neoadjuvant dual HER2-targeted therapy. The key findings suggest a strong correlation between achieving a pathologic complete response (pCR) or residual cancer burden (RCB) I in the breast and a high likelihood of having no residual disease in the axillary lymph nodes (ypN0).

The study observed that patients who attained breast pCR or RCB I after treatment had significantly higher rates of being ypN0, indicating a favorable response to the neoadjuvant therapy. For instance, in clinically node-negative (cN0) patients, all who achieved breast pCR were ypN0, while a substantial majority of those with RCB II-III were also ypN0. Similarly, in clinically node-positive (cN1) patients, those with breast pCR showed a 100% ypN0 rate, while those with RCB I or II-III had varying rates of ypN0.

The implications are significant, suggesting the potential for omitting axillary surgical staging in certain cases of HER2-positive breast cancer treated with active neoadjuvant HER2-targeted regimens, especially for those who achieve breast pCR or RCB I. This insight could influence the design of future trials and possibly spare patients from unnecessary surgeries if their response in the breast correlates strongly with nodal response.

Would you like further clarification on any specific aspect of the study or additional information?