Distinction of Chemotherapy-Induced Epithelial Atypia from Minimal DCIS with Chemotherapy Effect in HER2 Positive Patients Using HER2 Immunostaining
KL White, YY Chen, JT Rabban. UCSF, San Francisco, CA
Background: Chemotherapy can induce nuclear and cytoplasmic alterations in both neoplastic and benign breast epithelium. This can create diagnostic challenges in distinguishing minimal volume DCIS (defined as minimal duct/lobular expansion and minimal intraductal proliferation) from non-neoplastic epithelium. Two problematic settings are 1.) evaluating margins in neoadjuvant treated specimens and 2.) evaluating core biopsies of new lesions in patients with prior adjuvant treatment. In patients with untreated HER2 positive cancer, the invasive and in situ components are typically concordant by immunoexpression (IHC) while benign epithelium is negative. Thus, HER2 IHC could potentially be used to detect and distinguish minimal residual DCIS following chemotherapy from benign treatment atypia.
Design: We evaluated 203 patients with neoadjuvant chemotherapy-treated breast cancer to identify those with HER2 positive cancers on pre-treatment biopsy. Of this subset, 26 had residual pure DCIS and HER2 IHC (CB11, Novocastra, 1:200) was performed on the post-treatment specimens. Residual DCIS was classified as minimal DCIS if the involved ducts/lobules were not expanded when viewed at low magnification. DCIS was further classified by degree of nuclear atypia, by degree of atypical apocrine change, and by degree of obscuring healing changes (atypical ductal epithelium with obscuring chronic inflammation, histiocytes and ductal fibrosis and/or dilation).
Results: HER2 was strongly expressed in 22/26 residual DCIS cases, including 11/12 with minimal DCIS, most of which consisted only of single atypical cells with nucleocytomegaly interspersed between normal ductal epithelium. Of the HER2 negative residual DCIS cases, 3/4 showed classic low grade DCIS without treatment effects and 1/4 was minimal DCIS. All 8 cases with atypical apocrine change were HER2 positive. All 8 cases with features suspicious for healing DCIS contained HER2 positive cells embedded in the intraductal inflammatory reaction. The extent of minimal DCIS was underestimated on H&E stain compared to HER2 IHC in 5/26 cases. Among 10 lumpectomies with minimal residual DCIS requiring re-excision, 6/10 contained DCIS in the re-excision.
Conclusions: Positive HER2 IHC distinguishes minimal DCIS from benign atypia in chemotherapy treated HER2+ patients. H&E slides may underestimate extent of DCIS in this setting and attention should be aimed at atypical apocrine changes and healing ducts when evaluating neoadjuvant margins or core biopsies of new post-treatment lesions.
Tuesday, March 23, 2010 2:00 PM
Platform Session: Section B, Tuesday Afternoon