HER2-positive Stage I breast cancer: residual microinvasion after neoadjuvant T-DM1

What happened, in summary

This 75-year-old woman found a lump in the upper outer quadrant of her right breast. Mammography showed a 1.5 cm hypoechoic mass with calcifications. Core biopsy showed a poorly differentiated grade 3 invasive ductal carcinoma that was ER-negative, PR-negative, and HER2-positive with 3+ staining by immunohistochemistry. The clinical stage was Stage I. Because surgery was delayed during the COVID-19 pandemic, the multidisciplinary tumor board chose neoadjuvant ado-trastuzumab emtansine, or T-DM1, as a bridge to surgery. She received T-DM1 3.6 mg/kg IV every 3 weeks for 6 cycles. When operating rooms reopened, she underwent lumpectomy with sentinel lymph node biopsy rather than mastectomy. Pathology after surgery showed a very small residual focus of microinvasion, Stage I T1 measuring 0.1 cm or less, along with a few foci of ductal carcinoma in situ. The residual disease remained ER/PR-negative and HER2-positive by 3+ immunohistochemistry. Because there was still microinvasive disease, the team continued T-DM1 after surgery as adjuvant treatment, aiming for a total of 17 cycles. She also received adjuvant radiotherapy to 52.5 Gy. Her course is an example of near-complete response to neoadjuvant T-DM1 in early-stage HER2-positive breast cancer, with only minimal residual microinvasion at surgery. On follow-up after adjuvant therapy, she showed no evidence of disease. Her outcome contrasts with other patients in the same treatment series who progressed during T-DM1 bridging, underscoring why imaging and physical examination remained important during the delay to surgery and follow-up. The final pathology still showed only minimal invasive disease.