Abstract P5-08-15: Prognostic value of aldehyde dehydrogenase 1 (ALDH1) and tumor infiltrating lymphocytes (TIL) to predict the late recurrence in ER positive, HER2 negative breast cancer
Authors: Miyoshi Y , Shien T , Ogiya A , Ishida N , Yamazaki K , Horii R , Horimoto Y , Masuda N , Yasojima H , Inao T , Osako T , Takahashi M , Tomioka N , Hagio K , Endo Y , Hosoda M , Yamashita H 
Published: May 2016

Abstract
Introduction: Aldehyde dehydrogenase 1(ALDH1) is known to be cancer stem cell marker. Also, tumor infiltrating lymphocytes (TILs) are known to be prognostic factor for triple negative breast cancer. It is reported that these factors have the correlation with chemosensitivity. Meanwhile, the late recurrence (LRec; 5 years after primary surgery) of ER positive breast cancer is the major problem. Significance of expressions of ALDH1 and TILs in primary tumor as predictive factors for late recurrence in ER positive, HER2 negative breast cancer is still unknown.
Methods: ER-positive, and HER2-negative breast cancer patients who underwent surgery or received neoadjuvant chemotherapy between January 2000 and December 2004 were registered from nine institutes belonging the Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Society. For each LRec patient, approximately two matched control patients without relapse for more than ten years were selected. Expression of ALDH1 was assessed by immunohistochemistry. Positive ALDH1 was defined as tumor including more than 1% cancer cells with ALDH1 expression. TIL was assessed by single whole section according to Denkert's definition. A tumor showing high ki67 and/or low PgR expressions was categorized into Luminal B-like group.
Results: 639 patients (184 with early recurrence (ERec), 134 with LRec and 321 with no recurrence (NoRec)) were analyzed. The rates of positive ALDH1 in ERec, LRec and NoRec groups were 18%, 13% and 8%, respectively. ALDH1 positivity was significantly higher in ERec compared with NoRec group (p&lt;0.01). There was no significant difference between LRec and NoRec group (p=0.12). Positive ALDH1 showed significantly shorter DFS and OS in multivariate analyses (DFS: p=0.03, OS: p&lt;0.01). Especially, that was the significantly prognostic factor in the Luminal B like tumor with adjuvant or neoadjuvant chemotherapy (p=0.01), but not in those without any chemotherapy (p=0.53). High TILs in ERec, LRec and NoRec was 1.1%, 1.5% and 3.7%, respectively. There was no significant difference among three recurrent groups (p=0.13). High TILs was not significantly associated with DFS (p=0.09) and OS (p=0.72). However, there was significant correlation between High TILs and DFS in Luminal B like group (p=0.04) and ALDH1-negative group (p=0.02).
Conclusion: In ER-positive, and HER2-negative breast cancer, ALDH1 was an independent prognostic factor (a predictor of ERec, but not LRec). ALDH1 might be a predictor of benefit from chemotherapy in Luminal B like subtype. TILs was neither a predictor of ERec nor LRec. However, significance of TILs as prognostic factor might differ depending on subtypes and cancer stemness.
Citation Format: Miyoshi Y, Shien T, Ogiya A, Ishida N, Yamazaki K, Horii R, Horimoto Y, Masuda N, Yasojima H, Inao T, Osako T, Takahashi M, Tomioka N, Hagio K, Endo Y, Hosoda M, Yamashita H. Prognostic value of aldehyde dehydrogenase 1 (ALDH1) and tumor infiltrating lymphocytes (TIL) to predict the late recurrence in ER positive, HER2 negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-15.