Prognostic and predictive value of HER2 extracellular domain in patients with early and metastatic breast cancer treated with trastuzumab and lapatinib: Correlation with clinicopathological parameters and response
PubMed | Vito Fazzi Hospital Lecce
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
e11123 Background: HER-2 is a 185 kd protein composed of three domains: a cytoplasmatic domain, a transmembrane domain and an extracellular domain (ECD). The ECD of HER-2 can be cleaved from the surface of breast cancer cells by matrix metalloproteases and released into the serum where it is detectable using an enzyme-linked immunosorbent assay (ELISA). The role of high level of ECD as a surrogate of response to trastuzumab treatment in metastatic setting is debated. Its role as predictive factor of response to lapatinib in HER-2 +metastatic breast cancer (MBC) progressing to trastuzumab is unexplored. Moreover it is unknown if high level of ECD in the adjuvant setting of HER-2+ pts with early breast cancer (EBC) could be an early marker of resistance to trastuzumab.serum was obtained from 40 HER-2 +pts: 19 MBC/21 EBC. Serum ECD was determined using commercial ELISA-kits (Oncogene Science). This ELISA uses a measure of 15 ng/ml as the upper limit of normal. A median of 3 samples was collected (2-5) every three months (+/-1 month). Median age was 55 (34-77), median PS was 1 (0-2) median number of therapy performed for MBC was 2 (2-6), 11 of these pts were treated with lapatinib for metastatic disease.High level of ECD was detectable in 10 of MBC (25%) and in 4 of EBC pts (10%). Median PFS of MBC pts was 51 wks (CI 32-71). No relation was observed with high ECD levels and response to trastuzumab (p= 0.42) or lapatinib (p= 0.11) in MBC. HER-2 ECD level in EBC pts were not significantly associated with high istological grade (G1-G2 vs G3) (p=0.71), lymphonode involvement (N0-N1vsN2) (p= 0.63), degree of endocrine responsiveness respectively estrogen (<50% vs >50%) (p =0.5) and progesterone (<50% vs >50% )(p= 0.3), Ki67 high( 15%) vs low (<15%) (p=0.9).ECD measure in our experience did not predict benefit to trastuzumab or lapatinib. The prognostic value of ECD in EBC needs a larger population to be validated. Our study is ongoing and we have planned to enroll exclusively EBC pts in order to define the role of ECD in this setting, if any.