Outcomes of her2-positive early-stage breast cancer in the trastuzumab era: a population-based study of Canadian patients

Abstract

Breast cancer is heterogenous, with variable expression of the estrogen receptor (er), progesterone receptor (pr), and human epidermal growth factor receptor 2 (her2). Overexpression of her2 is generally considered a negative prognostic feature, but whether outcomes for her2-positive early breast cancer remain different from those for other subtypes in the era of trastuzumab-based adjuvant therapy is unknown.

Methods: Using a retrospective chart review, we compared overall survival (os) and relapse-free survival (rfs) in 3 groups of patients with early-stage breast cancer: er-positive or pr-positive (or both) and her2-negative ["hormone receptor-positive" (hr+)]; her2-positive (her2+); and er-negative, pr-negative, and her2-negative ["triple-negative" (tn)].

Results: In the 503 charts analyzed (332 hr+, 94 her2+, 77 tn), the 5-year os and rfs were, respectively, 94.2% and 87.2% for hr+ patients, 88.6% and 74.9% for her2+ patients, and 85.4% and 76.2% for tn patients. On multivariate analysis, the os for the her2+ subtype was similar to that for the hr+ subtype (hazard ratio:1.07; 95% confidence interval: 0.31 to 3.67 with hr+ as reference), but os was significantly worse for tn patients than for hr+ patients (hazard ratio: 4.37; 95% confidence interval: 1.56 to 12.24). In her2+ patients, the 5-year os and rfs trended better for patients with er+ or pr+ disease than for patients with er-negative and pr-negative disease (5-year os: 92.1% vs. 86.9%; 5-year rfs: 79.8% vs. 71.4%). Of her2+ patients, just 80.9% received trastuzumab, including 33.3% of her2+ patients with sub-centimetre tumours.

Conclusions: In the trastuzumab era, patients with her2+ and hr+ early breast cancer have similar outcomes, while tn patients experience a significantly worse os than either of the foregoing groups. Outcomes for her2+ patients may differ by er and pr status. Trastuzumab was underutilized in this cohort.

Keywords: adjuvant; her2-positive breast cancer; survival; trastuzumab.

FIGURE 1

Kaplan–Meier curves for overall survival by receptor group status. Log-rank chi-square for differences in survival across strata: χ² (df: 2) = 5.31, p = 0.070. er = estrogen receptor; pr = progesterone receptor; her2 = human epidermal growth factor receptor 2; TripNeg = triple-negative (er–, pr–, and her2-negative).

FIGURE 2

Kaplan–Meier curves for relapse-free survival by receptor group status. Log-rank chi-square for differences in survival across strata: χ² (df: 2) = 9.82, p = 0.007. er = estrogen receptor; pr = progesterone receptor; her2 = human epidermal growth factor receptor 2; TripNeg = triple negative (er–, pr–, and her2-negative).