Adjuvant trastuzumab with or without chemotherapy in stage 1 pT1N0 HER2+breast cancer: a National Cancer Database analysis

Purpose Approximately 20% of all breast cancers (BC) are HER2 amplified. In the APT trial, weekly paclitaxel/trastuzumab in node negative HER2+ BC with tumors < 3 cm was associated with a 7-year invasive disease-free survival of 93%. However, this was in the context of a non-randomized trial, and for pT1N0 HER2+ BC it remains unclear whether HER2 monotherapy would provide similar clinical outcomes to chemo-HER2 therapy. We hypothesized that adjuvant chemo-HER2 therapy would be associated with a modestly improved overall survival compared to HER2 monotherapy in patients with tumors < 2 cm. Methods In the National Cancer Database (2004-2017), patients with a primary diagnosis of pT1N0M0 HER2+ BC, were separated into two groups: (i) HER2 monotherapy, i.e., trastuzumab, and (ii) chemo-HER2 therapy. A 3:1 propensity match was performed to balance patient selection bias between the two different cohorts. Long-term overall survival (OS) was compared between both groups. Results A total of 23,281 patients met the criteria. 22,268 (96.7%) received chemo-HER2 therapy and 1013 (4.4%) received HER2 monotherapy. Propensity match identified 1995 patients who received chemo-HER2 therapy, and 666 who received HER2 monotherapy. After matching, adjuvant chemo-HER2 therapy was associated with a modest survival advantage over HER2 monotherapy (5-year OS 94.1% vs. 90.6%, P = 0.041). Conclusions Even though there is a modest OS advantage favoring adjuvant chemo-HER2 therapy in patients with pT1N0 HER2+ BC, HER2 monotherapy was associated with 5-year OS > 90%. Therefore, in select patients who have contraindications for cytotoxic chemotherapy, or decline adjuvant chemotherapy altogether, adjuvant trastuzumab monotherapy appears to be a reasonable alternative.