Abstract P6-09-18: Predictive factors of pathologic complete response to neoadjuvant chemotherapy in patients with Luminal HER2(-) local advanced breast cancer using the DMET microarray
Authors: Ruvalcaba-Limon E , Rodriguez-Cuevas S , Hidalgo-Miranda A , Villa-Romero A , Bautista-Piña V , Rebollar-Vega R , Fernandez-Lopez JC , Morales-Vasquez F 
Published: March 2017

Introduction

Patients with similar local advanced breast cancer (LABC) could respond different to neoadjuvant chemotherapy (NC). Luminal HER2(-) tumors have pathologic complete response (pCR) by 5-7%. Ki67, tumor grade and hormonal receptors, could be helpful but not enough to choice between NC vs. initial surgery. Response to drugs depends on enzymes involved in absorption, distribution, metabolism and elimination (ADME); the drug-metabolizing enzyme and transporter platform (DMET), could identify 1936 single nucleotide polymorphism (SNP) from 225 genes involved in ADME proccess.

Objective

To identify predictive factors to pCR in patients with Luminal HER2(-) LABC underwent NC, to distinguish wish patients could have a real benefit from NC.

Material and Methods

This is a prospective nested case control study (1:4) with LABC patients, pure invasive ductal carcinoma Luminal HER2(-) subtypes, and sequential NC (anthracyclines and taxanes). Cases were defined as patients with pCR (Residual Cancer Burden=0), and controls those without pCR. SNPs were evaluated from DNA of leucocytes using DMET microarrays by Affymetrix.

Bivariate analyses were used as appropriate. Microarrays were processed by the DMET analyzer console. OR and 95%CI were used to test association between pCR and variables with a non-conditional logistic regression analysis; p value ≤0.05 was considered statistically significant (two-sided).

Results

From 2005 to 2014, of 3762 treated patients, 287 women met inclusion criteria. We included 117 patients, 21 cases and 96 controls. Patients with pCR were 5 years younger than controls (45.4 vs 49.4), have more grade-3 tumors, (66.7 vs 22.3%), more Luminal B subtypes (90.5 vs 64.6%), lower expression of estrogen receptor (60 vs 80%) and higher Ki67 expression (65 vs 12%), all with p≤0.05. No differences in toxicity existed between groups.

In an initial screening procedure, 13 SNPs were identified, but only 4 SNPs (4 genes) are known to participate in ADME of antineoplastic agents. All pCR cases did not have the C/C allelic variant in the rs2072671 SNP (CDA gene); while in rs1883322 SNP (PPARD gene) all had T/T variant

SNPs identified in DMET microarray known to participate with antineoplastic agentsGENESNPAllelic variantpCR, n=21No pCR, n=96pDPYDrs17376848T/T13 (61.9%)83 (86.4%)0.007  C/T8 (38.1%)11 (11.4%) CDArs2072671A/A6 (28.5%)51 (53.1%)0.013  A/C15 (71.4%)36 (37.5%)   C/C09 (9.3%) PPARDrs1883322T/T21 (100%)69 (71.8%)0.022  C/T022 (22.9%)   C/C05 (5.2%) GSTM3rs7483A/A7 (33.3%)20 (20.8%)0.024  A/G13 (61.9%)43 (44.7%)   G/G1 (4.7%)33 (34.3%) pCR= pathologic complete response

After logistic regression analysis, pCR predictive factors were the presence of grade-3 tumors OR=6.66 (95%CI=1.67-26.56), Ki67 ≥14% OR=15.45 (95%CI=1.71–138.86), premenopausal status OR=6.540 (95%CI=1.50–28.38) and A/A or A/G allele in rs7483 SNP (GSTM3 gene) OR=19.16 (95%CI=1.97–185.93).

Conclusions

Genetic variability encoded in the DMET-chip, could be helpful as a predictive factor of pCR in patients with Luminal HER2(-) LABC, but only in combination with other factors such as grade-3 tumors, elevated Ki67, and premenopausal status.

Citation Format: Ruvalcaba-Limon E, Rodriguez-Cuevas S, Hidalgo-Miranda A, Villa-Romero A, Bautista-Piña V, Rebollar-Vega R, Fernandez-Lopez JC, Morales-Vasquez F. Predictive factors of pathologic complete response to neoadjuvant chemotherapy in patients with Luminal HER2(-) local advanced breast cancer using the DMET microarray [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-18.