Introduction: Metastatic breast cancer (MBC) is considered an incurable disease. However, long-term survival is increasingly observed in HER2-positive disease since the introduction of trastuzumab. We explored factors associated with long-term survival in a retrospective series at our Institute.

Methods: All patients with histologically proven HER2-positive (3+ score by IHC or HER2 amplification) MBC treated starting first-line trastuzumab-based palliative therapy between January 2003 to January 2013 were included. Patients were identified from the Institute's tumor registry and data were collected from patient records. The primary endpoint was overall survival. Kaplan-Meier survival estimates were calculated and multivariable survival analyses were performed to identify independent prognostic factors. Radiologic complete response (CR) was a secondary endpoint.

Results: We identified 113 patients with a median age at diagnosis of MBC of 52 years (range 27-82). Median follow-up for MBC was 39 months (range 2-148 months). Thirty-eight percent presented with synchronous metastases; 62% had recurrent disease of whom 42% had received prior trastuzumab as part of (neo-)adjuvant treatment. First-line palliative treatment consisted of trastuzumab plus vinorelbine (56%), a taxane (28%), capecitabine (10%), other chemotherapy (3%), or endocrine therapy (2%), and resulted in a CR in 27 patients (24%). In addition, one patient achieved CR to third-line therapy. Most patients with CR had received trastuzumab with a taxane (57%) followed by vinorelbine (32%). Fourteen out of 28 patients with CR are still alive without evidence of disease at a median follow-up of 91 months (range 23-148 months), of whom 8 still receive trastuzumab. Fourteen patients had disease relapse (8 on maintenance trastuzumab, 6 after discontinuation). Overall, 35 patients (31%) survived more than 5 years. Factors associated with long-term survival in univariable analyses were oligo-metastatic disease (1-3 distant metastases), synchronous metastases, no skin or brain metastases, no prior (neo-)adjuvant trastuzumab, first-line palliative treatment with trastuzumab and taxanes, and achieving a radiologic CR on treatment (see table 1). Achieving CR and the absence of skin metastases remained significant factors in multivariable analyses.

Conclusion: Thirty-one percent of patients with metastatic HER2-positive MBC survive over 5 years. Long-term response is particularly seen in patients who achieve a complete radiologic response on first-line treatment. This finding supports a strategy to administer the most effective agents as first line treatment, as is often but not always applied in clinical practice.

Table 1. Prognostic factors associated with overall survival

    Univariable     Multivariable   
  HR 95% CI p HR 95% CI p 
Synchronous metastases             
No         
Yes 0.44 (0.27-0.70) <0.001 0.80 (0.46-1.40) 0.43 
Oligo-metastatic disease             
No         
Yes 0.37 (0.22-0.62) <0.01 0.66 (0.36-1.17) 0.14 
Skin metastases             
No         
Yes 5.40 (2.91-10.01) <0.01 4.10 (2.08-8.14) <0.01 
Brain metastases             
No         
Yes 2.25 (1.03-4.93) 0.04 1.46 (0.55-3.98) 0.45 
(Neo-)adjuvant trastuzumab             
No         
Yes 1.87 (1.16-2.99) 0.01 1.66 (0.93-2.96) 0.09 
Trastuzumab + taxane             
No         
Yes 0.54 (0.32-0.89) 0.02 0.69 (0.40-1.20) 0.19 
Complete radiologic response             
No         
Yes 0.13 (0.06-0.29) <0.01 0.22 (0.09-0.53) 0.001 
    Univariable     Multivariable   
  HR 95% CI p HR 95% CI p 
Synchronous metastases             
No         
Yes 0.44 (0.27-0.70) <0.001 0.80 (0.46-1.40) 0.43 
Oligo-metastatic disease             
No         
Yes 0.37 (0.22-0.62) <0.01 0.66 (0.36-1.17) 0.14 
Skin metastases             
No         
Yes 5.40 (2.91-10.01) <0.01 4.10 (2.08-8.14) <0.01 
Brain metastases             
No         
Yes 2.25 (1.03-4.93) 0.04 1.46 (0.55-3.98) 0.45 
(Neo-)adjuvant trastuzumab             
No         
Yes 1.87 (1.16-2.99) 0.01 1.66 (0.93-2.96) 0.09 
Trastuzumab + taxane             
No         
Yes 0.54 (0.32-0.89) 0.02 0.69 (0.40-1.20) 0.19 
Complete radiologic response             
No         
Yes 0.13 (0.06-0.29) <0.01 0.22 (0.09-0.53) 0.001 

Citation Format: Steenbruggen TG, van Ramshorst MS, Stouthard JML, Rodenhuis S, Linn SC, Sonke GS, Smorenburg CH. Long-term survival in HER2-positive metastatic breast cancer: The first blow is half the battle [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-30.