P3-05-02: Subtype-Specific Co-Occurrence of Atypical Hyperplasia and In Situ Carcinoma with Invasive Breast Cancers.
Authors: AJ Kovatich, L Kvecher, Y Chen, A Bekhash, JA Hooke, CD Shriver, RJ Mural, H Hu
Journal: Cancer Research (2011)

Abstract Background Atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), and ductal carcinoma in situ (DCIS) are considered risk factors for the development of invasive breast cancer (IBC). The co-occurrence of these lesions with IBC may provide insights into cancer initiation and development. IBC subtypes have distinct clinicopathological features. A clinically practical IHC-based subtyping classification has been developed based on the expression of ER, PR, HER2, and Ki67, defining Luminal A (LA), Luminal B (LB), HER2+, and Triple Negative (TN) subtypes. The Walter Reed Army Medical Center (WRAMC), through the Clinical Breast Care Project (CBCP), has enrolled over 500 IBC subjects with single pathologist review and central lab analysis. The co-occurrence of ADH, LCIS, and DCIS will be studied in relation to IBC subtypes. Methods: Subjects were enrolled following IRB-approved protocols. IBC patients enrolled at WRAMC were selected and their clinical and pathology data were reviewed. ER and PR positivity is defined as &amp;gt; 5% nuclear staining. The HER2 result is negative if the IHC=0 or 1+ and positive if IHC=3+. For IHC=2+, the FISH result determines the final HER2 status. Ki67 is considered positive if nuclear staining is &amp;gt;= 15%. For IBC subtypes, LA is ER+/HER2−/Ki67-; LB is either ER+/HER2−/Ki67+, or ER+/HER2+; HER2+ is ER-/PR-/HER2+; TN is ER-/PR-/HER2−. Statistical analysis was performed using SAS, and the Chi-Square test was used for categorical data analysis supplemented by the Fisher's Exact test where appropriate. For age analysis, ANOVA was performed with Bonferroni adjustment for multi-pair t-test. Results: A total of 459 IBC patients were identified and categorized into LA (41.6%), LB (27.7%), HER2+ (10.2%), and TN (20.5%). Many of the previously reported subtype-specific characteristics were confirmed. Age at diagnosis varied by subtype (p=0.0034) with LA being the oldest (Mean±SD=59.9+12.5 years) and TN the youngest (54±12.6 years, p=0.0048). Ethnicity distribution of African American (AA) relative to Caucasian American patients varied significantly in subtypes with AA=18% in LA, 31% in LB, 32% in Her2+, and 42% in TN (p=0.0008). The grade, the AJCC stage and its components T and N were all significantly different among the subtypes (p ranges from &amp;lt;0.0001 to 0.0020). The grades and stages were consistently lowest for LA, highest for HER2+ and TN. We further found that the co-occurrence of ADH, DCIS, and LCIS with IBC were subtype-specific with the following distributions: ADH—LA (25.1%), LB (18.9%), HER2+ (0%), and TN (6.4%) (p&amp;lt;0.0001, n=78); DCIS—LA (63.4%), LB (76.4%), HER2+ (80.9%), and TN (58.5%) (p=0.0039, n=311); LCIS—LA (36.7%), LB (19.7%), HER2+ (4.3%), and TN (6.4%) (p&amp;lt;0.0001, n=103). Discussion: By including Ki67 in IHC-based IBC subtyping we confirmed many subtype-specific clinico-pathological characteristics in the CBCP WRAMC population. We further report subtype-specific co-occurrences of ADH, DCIS, and LCIS. These co-occurrence patterns may reveal distinct developmental mechanisms between the different subtypes of IBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-05-02.