Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)



First Advisor

Lajos Pusztai


Background: An increasing number of metastatic HER2 positive cancers are diagnosed as de novo stage IV disease. We hypothesize that a subset of these patients, who achieve complete clinical response or no evidence of disease (NED) status after multi-agent HER2-targeted treatments may have long progression free (PFS) and overall survival (OS).

Methods: 483 patients with de novo stage IV HER2 positive breast cancer diagnosed between 1998-2015 were identified through the medical records at Yale and MD Anderson Cancer Centers. Treatment, clinical variables and survival were extracted and compared between those who achieved NED status and those who did not.

Results: All patients received trastuzumab and 94 (20%) also received pertuzumab as first line therapy. The median OS was 5.5 years (95% Cl:4.8-6.2). Sixty-three patients (13.0%) achieved NED, their PFS and OS were 100% and 98% (95% CI:94.6%-100%) at 5 years and remined the same at 10 years. For patients with non-NED (n=420), the PFS and OS rates were 12% (95% CI:4.5%-30.4%) and 45% (95% CI:38.4%-52.0%) at 5 years, and 0%, and 4% (95% CI:1.3%-13.2%) at 10 years. There was no difference in age, grade, race, year of diagnosis, ER status, treatment distribution, or radiation between the NED and non-NED groups. NED patients more frequently had solitary metastasis (79% vs 51%, p=0.005) and surgery to resect cancer (59% vs. 22%, p≤0.001). In multivariate analysis, NED status (Hazard ratio (HR):0.014, P=0.0002) and hormone receptor positive status (HR:0.72; P=0.04) were associated with prolonged OS.

Conclusion: Achieving NED status may be an important therapeutic goal for de novo, stage IV, HER-2 positive MBC.

Open Access

This Article is Open Access