Abstract P2-06-16: The impact of ALDH1 on chemo-resistance and prognosis according to intrinsic subtype in breast cancers
Authors: Kida Kumiko , Ishikawa Takashi , Yamada Akimitsu , Narui Kazutaka , Sugae Sadataka , Tanabe Mikiko , Ichikawa Yasushi , Endo Itaru 
Published: May 2015

[Background]Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker. The clinical significance of ALDH1 as a chemo-resistant and prognostic indicator has been reported recently. However, the analysis according to each intrinsic subtype was not reported.

[Aims] To investigate the impact of ALDH1 on chemo-resistance and prognosis according to intrinsic subtypes in invasive breast cancers.

[Methods]

1) Patients and tumor specimens; A total of 653 primary breast cancer patients were enrolled in this study from 2004 to 2013 at the Yokohama City University Medical Center in Japan. We performed immunohistochemical analyses using paraffin-embedded core needle biopsy sections prior to the treatment.

2) Correlation of ALDH1 with clinicopathological factors;

Analyses were performed to investigate association of ALDH1 expression with other biomarkers and clinicopathological factors in breast cancers. Age, histologic type, tumor size, nodal status, ER/PgR/HER2 status, nuclear grade, Ki67, Topo2, p53, CK5/6 and EGFR were observed.

3) Neoadjuvant patient cohort study

234 breast cancer patients receiving neoadjuvant chemotherapy were enrolled. The correlation between ALDH1 and pathological complete response (pCR) rate was investigated in each intrinsic subtype.

4) Prognostic cohort study

We performed a Cox analysis of disease free survival and overall survival of all 653 cases according to each subtype, taking account of clinicopathological factors.

[Results]

ALDH1 expression in tumor cells was seen in 139 of 653 cases (21.3%). The ALDH1 expression correlated significantly with tumor size, clinical node metastasis, clinical staging, nuclear grade and HER2 status positively, ER and PgR status negatively. ALDH1 expression was significantly seen in HER2-positive cancers and triple negative type.

In neoadjuvant study, we analyzed 234 patients treated with neoadjuvant chemotherapy including 63 luminal type, 20 luminal-HER2 type, 45 HER2-enriched type and 106 triple negative type. The pCR rate was significantly lower in patients with ALDH1-positive cases (13.5%vs.30.3%,p=0.003). In multivariate analysis, ALDH1 and ER are correlated with pCR rate significantly. According to the intrinsic subtypes, the correlation between pCR and ALDH1 expression was extremely significant in triple negative type (p=0.003). In HER2 positive type, ALDH1 expression had tendency with low pCR, but with no significance. In luminal type, two patients achieved pCR and both had no ALDH1 expression.

In prognostic analysis, patients with ALDH1 expression had significantly poor disease free survival (DFS; p&lt;0.001) and overall survival (OS; p=0.044). In the multivariate COX regression model, ALDH1 expression was an independent prognostic indicator of DFS (p=0.033), but not significant predictor of OS (p=0.124). According to each intrinsic subtypes, ALDH1 had a higher impact on prognosis of luminal type ,though not significant on triple negative type.

[Conclusions]

Breast cancers with ALDH1 expression posse biologically aggressive phenotypes that tend to have a poor prognosis. Chemoresistance was significantly seen in ALDH1-positive triple negative type, on the other hand, impact on prognosis was seen in luminal type more highly than triple negative type.

Citation Format: Kumiko Kida, Takashi Ishikawa, Akimitsu Yamada, Kazutaka Narui, Sadataka Sugae, Mikiko Tanabe, Yasushi Ichikawa, Itaru Endo. The impact of ALDH1 on chemo-resistance and prognosis according to intrinsic subtype in breast cancers [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-16.