Proliferation rate and breast cancer subtype, but not ALDH1 expression, predict pathological response to neoadjuvant chemotherapy in locally advanced breast cancer

Abstract

For locally advanced breast cancer, pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) is associated with good disease-free survival. In several studies, response to chemotherapy according to various parameters has shown strong inter-individual variability. We investigated whether different prognostic factors, including ALDH1 expression, might predict response to NACT in female patients with locally advanced breast carcinoma. ER, PR, Her2/neu, Ki-67 and ALDH1 immunohistochemistry were performed on the initial biopsy and subsequent resection specimens. Residual tumour burden was calculated in post NACT resection specimens using residual cancer burden (RCB) protocol. Of our cohort of 66 patients, 24 (36 %) achieved pCR. Triple negative phenotype and high Ki-67 proliferative index (>40 %) were significantly associated with good response to NACT. ALDH1 expression in tumour epithelial (20 %) or stromal (44 %) cells did not correlate with tumour grade, molecular subtype, proliferative index or NACT response. However, epithelial and stromal ALDH1 expression was significantly increased in residual tumour after NACT. In conclusion, triple negative phenotype and high proliferative index, but not ALDH1 expression, are predictive of good pathological response to NACT. Increased ALDH1 expression following NACT might be associated with a higher probability of recurrent disease.

<p>The Evaluation of Magee Equation 2 in Predicting Response and Outcome in Hormone Receptor-Positive and HER2-Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy</p>

“…24,25 Luminal breast cancer subtype had lower response to NAC when compare to other subtypes. 26,27 Although there were higher proportion of T4 breast cancer recruited in this current study, the rate of pCR in the current study was similar to the recent report of clinically node-positive breast cancer receiving NAC. 25 However, approximately 70% of the patients received neoadjuvant AC regimen which resulted in lower response when compare to the addition of taxane-based regimen.…”

Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence

“…This observation suggests that the presence of ALDH1-positive cancer stem cells correlates with early recurrence and shorter survival. Researchers in another study found patients with ALDH1-positive tumors to have poorer outcomes than those with ALDH1-negative tumors [ 6 , 20 , 26 , 28 – 31 ]. However, the authors of other reports noted no association of ALDH1 expression with poor outcomes [ 13 , 21 , 32 , 33 ].…”

Aldehyde dehydrogenase 1 as a predictor of the neoadjuvant chemotherapy response in breast cancer

“…ALDH1 can inactivate integral agents of NAC; therefore, breast cancer patients with high ALDH1 expression may have a low survival rate [ 20 ] and increased risk of recurrence. [ 10 ] Two other studies on all types of breast cancer also reported that the ALDH1 protein is a potential predictive marker of early local tumor recurrence and distant metastasis. [ 21 , 22 ]…”