The protein expression and gene amplification of HER2 were sometimes found heterogeneous within tumors in HER2-positive breast cancers. The degree of HER2 amplification was not correlated with efficacy of trastuzumab. Thus, it is assumed that the heterogeneity of HER2 may be associated with some specific biological behavior.
To investigate whether the intratumoral heterogeneity of HER2 expression may associate with malignant potential in cases with HER2 2+.
We selected breast cancer patients with HER2 2+ by immunohistochemistry who received neoadjuvant chemotherapy without trastuzumab and underwent surgery between January 2004 and December 2010. In core-needle biopsy specimens, HER2 2+ cases were divided into 2 groups by the staining pattern, overall and partially stained cases. We defined as HER2 monotonous-type (HER2 mono) and HER2 heterogeneous-type (HER2 hetero), respectively.
Thirty-eight cases with HER2 2+ were examined in total. HER2 hetero and HER2 mono were found in 20 and 18 cases, respectively. Patient characteristics were not different between 2 groups. The median age: 55 years and 54 years, stage III: 80% and 67%, stage III: 20% and 33%, ER-positivity: 80% and 78%, PgR-positivity; 65% and 67%. HER2-FISH positivity: 15% and 17%. At the median follow-up of 69.1 months, recurrent diseases were found in 13% (5/38) of cases, 4 cases in HER2 hetero and 1 case in HER2 mono.
This pilot study suggests that the intratumoral heterogeneity of HER2 may be associated with malignant potential of HER2 2+ breast cancer. We have started to examine the association of the heterogeneity with biological behavior in cases with HER2 3+.
Clinical trial identification
All authors have declared no conflicts of interest.