170P - Clinical presentations and prognosis of HER2-low breast cancer in Taiwan

Background

With the advent of the novel ADC agents, HER2-low breast cancer (BC) has been recognized. We use the Taiwan Cancer Registry (TCR) database and Taipei Veterans General Hopspital (TPE-VGH) database to evaluate the clinical presentations and prognostic outcomes for this spectrum.

Methods

HER2-low was defined as IHC 1+ or 2+ with ISH-negative; HER2-zero was defined as IHC 0. 133546 sides of BC per subject were collected from TCR (2007∼2017); while 4200 of BC patients were enrolled from TPE-VGH (2000∼2016). Propensity matching was applied. Analyses were conducted on PFS, OS, recurrent and metastatic features between HER2-low/zero, along with subtle subgroup analyses.

Results

The safety analysis group comprised 37195 HER2-negative BC from TCR and 4200 from TPE-VGH. Proportion of HER2-low and HER2-zero was 73.6% and 26.4%(TCR), with 73.9% and 26.1%(TPE-VGH). In TCR database, HER2-low was associated with slightly younger age, less early stage (stage 0 or I <50%), more HR+ and fewer grade 3 disease compared with HER2-zero. The OS & PFS were strongly related to HR positivity. While no OS difference noted between HER2-low/zero in overall population, by stage, by grade, before or after propensity matching. As coming to recurrence and metastatic pattern, there was no difference between HER2-low/zero. In TPE-VGH database, there was no differences in terms of diagnostic age, stage, grade, PFS or OS between HER2-zero/low. However, it is noteworthy that among HER2-low BC, patients with HR+/IHC 2+ had more grade 3 (P<0.001), advanced stage (P<0.001) and more nodal positive (P<0.001). IHC 2+ BC also had worse OS (p=0.05), and the survival discrepancies was more profound in HR+ subgroup (P= 0.04). After propensity matching, no OS difference was observed across HER2 0, 1+, 2+. This suggest that once balanced for key confounders, the impact of HER2 expression on survival outcomes becomes indistinguishable.

Conclusions

We noted that HR+/HER2 2+ BC patients have higher stage, higher grade, which aligns with the high-risk criteria in MonarchE trial. In the era without adjuvant CDK4/6 inhibitors, this subgroup indeed faced a worse prognosis. However, after propensity matching, no OS difference was observed, showing that HER2-low status is not a prognostic marker for Taiwanese breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

L-M. Tseng.

Funding

Melissa Lee Cancer Foundation.

Disclosure

All authors have declared no conflicts of interest.