The Lancet Oncology: VOLUME
24, ISSUE 3, P273-285, MARCH 2023
Background
We aimed to report
on long-term outcomes of patients with small, node-negative, HER2-positive
breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish
potential biomarkers to predict prognosis.
Methods
In this open-label,
single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm),
node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology
Group performance status of 0–1, were recruited from 16 institutions in 13
cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m2)
with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2
mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once
every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab.
The primary endpoint was 3-year invasive disease-free survival. Here, we report
10-year survival outcomes, assessed in all participants who received
protocol-defined treatment, with exploratory analyses using the HER2DX genomic
tool. This study is registered on ClinicalTrials.gov,
NCT00542451, and is closed to accrual.
Findings
Between Oct 29,
2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant
paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment
was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%)
was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and
272 (67·0%) had hormone receptor-positive disease. After a median follow-up of
10·8 years (IQR 7·1–11·4), among 406 patients included in the analysis
population, we observed 31 invasive disease-free survival events, of which six
(19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new
contralateral breast cancers, six (19·4%) were distant recurrences, and ten
(32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3%
(95% CI 88·3–94·4), 10-year recurrence-free interval was 96·3% (95% CI
94·3–98·3), 10-year overall survival was 94·3% (95% CI 91·8–96·8), and 10-year
breast cancer-specific survival was 98·8% (95% CI 97·6–100). HER2DX risk score
as a continuous variable was significantly associated with invasive disease-free
survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00–1·52];
p=0·047) and recurrence-free interval (1·45 [1·09–1·93]; p=0·011).
Interpretation
Adjuvant paclitaxel
and trastuzumab is a reasonable treatment standard for patients with small,
node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help
to refine the prognosis for this population.
