Disease progression pattern in metastatic breast cancer patients treated with anti-HER2 therapies

Purpose: Over the last decade a dramatic improvement in the treatment and prognosis of human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer (MBC) has been achieved. This study aimed to describe pattern, timing of metastases, and time to progression (TTP) of MBC patients (pts) treated with multiple lines of therapy with trastuzumab and/or lapatinib. Methods: Clinical-pathologic features, treatment-lines and metastatic sites were collected from the institutional database; TTP was evaluated for each treatment-line. A meta-analysis of treatment-line estimates was performed; Q test and I²-index were used to detect and estimate heterogeneity. Cox’s proportional hazards model and Fine and Gray’s proportional subhazards model in a competing risks setting were used to detect differences in hazard rate and to estimate relative risks. Results: 112 pts were analyzed. The median number of treatment-lines administered was 6 (range 1–17) and 524 (86 %) disease progression events were observed (median follow up 4.2 years). Distribution of metastases at baseline remained consistent across all lines. Having a given site affected by metastasis was a major risk factor of progression in that site. Hormone-receptor-positive pts resulted more likely to progress on bone (HR = 1.88). Elderly pts were less likely to progress on CNS (HR = 0.73). Median TTP resulted superior to 5 months up to the 6th line of treatment, reaching a plateau at the 9th treatment-line. Conclusions: These data suggest that risk factors for progression in HER2 positive MBC do not significantly differ between various distributions of metastases, and that MBC pts benefit from anti-HER2 therapy even in late treatment-lines.