Circulating HER2 extracellular domain and response to chemotherapy in metastatic breast cancer

Abstract EN

Purpose : The present study was designed to demonstrate the association between HER2 and chemotherapy resistance in patients with metastatic breast cancer.

Patients and methods : we performed a prospective assessment of the predictive value of the circulating HER2 extracellular domain (ECD) in patients with metastatic breast carcinoma using paclitaxel and doxorubicin.

Serum samples were collected from 45 patients with metastatic breast carcinoma before first-line chemotherapy for meta-static disease and the levels of circulating HER2 ECD were measured using an enzyme immunoassay.

Immuno-histochemistry with anti-HER2 monoclonal antibody CB11 was used to assess the expression of HER2 in the primary tumors.

Results : when 450 fmol / ml was used as a cutoff, 18 patients (40 %) had elevated HER2 ECD levels.

Elevated levels of circulating HER2 ECD were associated with the expression of HER2 in the primary tumor tissue and with the metastatic tumor burden (evaluated with the marker CA 15-3 ; p = 0.032 and p = 0.002, respectively) but not with variables such as menopausal status, stage at diagnosis, previous adjuvant therapy, or the number of metastatic sites.

The levels of circulating HER2 ECD correlated inversely with the response to treatment.

The probability of obtaining a complete response to chemotherapy was significantly lower (p = 0.021) in patients with elevated HER2 ECD levels (0 % ; 95 % confidence interval, 0-13 %) in comparison with patients with non-elevated HER2 (26.9 % ; 95 % confidence interval, 12-45 %).

In addition, the duration of clinical response was significantly shorter in patients with elevated HER2 ECD, in comparison with the cases with non-elevated HER2 (7.5 versus 11 months ; p = 0.035).

The abbreviations used are ECD : Extracellular domain.

CAF : Cyclophosphamide-Adriamycin-5-fluorouracil.

CMF : Cyclophosphamide-methotrexate-5-fluorouracil.

CALGB : Cancer and leukemia group B.

PAF : L-phenylalanine mustard-5-fluorouracil-doxorubicine.

CI : Confidence interval.

Conclusion : in conclusion, elevated levels of circulating HER2 ECD in patients with metastatic breast cancer correlate with reduced efficacy of a paclitaxel-doxorubicin chemotherapy combination.

We suggest that the poor response rate associated with HER2 expression in advanced breast cancer may not be reversed by aggressive chemotherapy alone.