Locoregional and symptomatic response to neoadjuvant dual HER2 blockade with chemotherapy in HER2-positive breast cancer: a pilot study

Dual HER2 blockade with trastuzumab and pertuzumab in combination with chemotherapy has improved pathological complete response (pCR) rates in HER2-positive breast cancer in randomized trials. However, real-world pilot data on locoregional and symptomatic outcomes in patients receiving this regimen before surgery are limited. This was a prospective pilot study including 20 patients with HER2-positive breast cancer treated with neoadjuvant trastuzumab, pertuzumab, and chemotherapy. Patients were assessed clinically and radiologically at baseline and following completion of neoadjuvant therapy. Primary endpoints were locoregional response (tumor shrinkage, nodal downstaging, and operability) and symptomatic improvement (pain, heaviness, and nipple/skin changes). All patients subsequently underwent definitive surgery. Median age was 46 years (range 32-65). Most patients presented with locally advanced disease, and 70% had palpable axillary nodes. Following neoadjuvant therapy, the overall clinical response rate was 85%, with 25% achieving complete clinical response and 60% partial response. Median tumor reduction was approximately 50%. Nodal downstaging was seen in 60%, with complete nodal response in 30%. Symptomatic improvement was reported in 80% for pain, 70% for heaviness, and 60% for skin/nipple changes. All patients proceeded to surgery, and pCR was achieved in 25%. The regimen was well tolerated, with no major cardiac events or treatment-related mortality. Neoadjuvant dual HER2 blockade with chemotherapy is feasible in HER2-positive breast cancer, achieving high clinical response rates, meaningful symptomatic improvement, and acceptable safety in this pilot study. These findings provide early single-center, prospective pilot evidence supporting dual HER2-targeted neoadjuvant therapy, with implications for operability and patient-centered outcomes. Larger multicentre studies are needed to validate these results.