Low HER2-expression to predict impaired activity of endocrine therapy in patients with estrogen-receptor (ER) positive metastatic breast cancer (MBC).

Abstract

573 Background: ER cross-activation by growth-factor signalling causes resistance to endocrine therapy (ET) in patients (pts) with Her2-positive MBC. Moreover, low levels of Her2-expression (Her2 1+; Her2 2+ without gene amplification), may result in reduced efficacy of ET in early breast cancer pts. In a recently published study, these tumours had a less favourable outcome as compared to tumours with a Her2-score of 0. Here, we investigated if low levels of Her2-expression could predict for shorter progression-free survival (PFS) in MBC pts on ET. Methods: PFS on first-line ET was chosen as primary endpoint and estimated with the Kaplan-Meier method. To test for differences between PFS curves, the log-rank test was used. Association of the following variables with PFS was investigated: low Her2-expression, grading, level of ER-expression, progesterone-receptor status, Ki67 (cut-off ≤20%), prior adjuvant ET, and presence of visceral metastases. For an estimated superiority of 40% in terms of PFS in favour of the Her2-negative group, a sample of 130 pts in two groups was needed in order to rule out the null-hypothesis with a 80% power and a two-sided α of 0.025. Results: A total number of 320 ER-positive MBC pts were identified from a breast cancer database; 170 pts were available for this analysis. Median PFS on first-line ET was 11 months (m) (8.56-13.44), corresponding numbers for second-line were 6 m (4.65-7.36), and third-line 4 m (1.52-6.48), respectively; median OS from diagnosis of MBC was 58 m (48.15-67.86). None of the variables investigated were significantly associated with first-line PFS. Second-line PFS, however, was significantly shorter in pts with grade 3 tumours and prior adjuvant ET; a trend towards shorter PFS was observed in high proliferating tumours. Conclusions: In this chart review, low levels of Her2 expression did not predict for shorter PFS in pts receiving ET; PFS in different treatment lines was well in line with data from clinical trials. High tumour grading and prior adjuvant ET were associated with accelerated onset of resistance, rendering those patients candidates for early combination of ET with targeted treatment approaches.