HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy

Abstract

Recent clinical data have suggested that the efficacy of tamoxifen in reducing the risk of local recurrence following lumpectomy and radiation therapy in patients with ductal carcinoma in situ (DCIS) is limited to patients with estrogen receptor (ER)-positive lesions. However, it is currently not known if HER2 protein overexpression might be associated with reduced tamoxifen benefit in patients with ER-positive DCIS, as has been suggested in patients with ER-positive invasive breast cancer and in preclinical models. Moreover, the frequency of HER2 overexpression in ER-positive ductal carcinoma in situ has not been previously evaluated in detail. To address this issue, we studied ER expression and HER2 overexpression in 148 cases of DCIS using a sensitive double immunostaining technique and assessed the frequency of ER expression and HER2 overexpression in relation to each other and in relation to DCIS grade. Overall, ER expression was seen in 114 cases (77%) and HER2 protein overexpression was seen in 42 cases (28%). Of 114 ER-positive ductal carcinoma in situ, 14 (12%) showed concurrent HER2 protein overexpression, and all 14 of these DCIS lesions were of high nuclear grade. In addition, in all 14 ER-positive DCIS cases that showed HER2 overexpression, double immunostaining demonstrated that ER and HER2 protein were coexpressed by the same neoplastic cells. We conclude that a subset of ER-positive DCIS show concomitant overexpression of HER2 protein.Whether or not HER2 overexpression is associated with a diminished response to tamoxifen in patients with ER-positive DCIS will require investigation in clinical outcome studies.

c-erbB-2 and the “triple-state” in early breast carcinomas

“…A follow-up period extending over 20 year was available at the Certainly, our study became possible because the archival material retained an excellent antigenic reactivity with tumors reaching a positive expression of 66.3% for ER, 45.7% for PgR, and 30.2% for c-erbB-2 (Her2/neu). These results, which compare favorably with recent reports [9,11,12,[20][21][22], are not unexpected as antigen reactivity has been demonstrated in tissues after preservation in paraffin wax for two decades or more without affecting adversely the sensitivity or specificity of the immunohistochemical method [23,24]. Nowadays, procedures have been further improved with antigen retrieval methods being almost optimal.…”

Integrated Genomic and Transcriptomic Analysis of Ductal Carcinoma In situ of the Breast

“…In our series of 57 DCIS, most tumors (56%) belonged to the luminal group based on ER expression and the absence of ERBB2 overexpression. The second group of tumors comprised ERBB2 overexpressing DCIS (37%) that were mostly high grade (81%) and ER negative/PR negative (90%) in agreement with previous reports showing that ERBB2 overexpression is rare in ERpositive DCIS (37). A third small group was composed of three triple-negative DCIS (5%) with only one case demonstrating a clear basal-like immunophenotype (2%) with positive staining for keratin 5/6 and epidermal growth factor receptor, confirming that the recently recognized basal-like DCIS group is a rare entity among pure DCIS (6-10% of cases; refs.…”

Ductal Intraepithelial Neoplasia: Postsurgical Outcome for 1,267 Women Cared for in One Single Institution over 10 Years

“…Interestingly, the beneficial effect of the drug is observed after a relatively short exposure time (22 months), and this may have important implications in terms of overall quality of life and adverse events in both pre-and postmenopausal women. One hundred ninety-eight (15%) patients showed the simultaneous presence of ER ϩ and HER-2 overexpression, a frequency similar to what has previously been reported [36]. HER-2/neu overexpression has been associated with a poor prognosis and may predict resistance to tamoxifen in the adjuvant setting [37,38].…”