qRT-PCR-based DNA homologous recombination-associated 4-gene score predicts pathologic complete response to platinum-based neoadjuvant chemotherapy in triple-negative breast cancer.

Abstract

PURPOSE:

Cumulative evidence suggests that the addition of platinum agents as neoadjuvant chemotherapy (NACT) could improve the pathologic complete response (pCR) rate in triple-negative breast cancer (TNBC). We aimed to develop a DNA homologous recombination (HR)-associated gene expression score to predict tumor sensitivity to platinum-based NACT in TNBC.

METHODS:

A retrospective cohort of 127 patients who were diagnosed with TNBC and received platinum-based NACT in Fudan University Shanghai Cancer Center from 2012 to 2017 was included in this study. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the expression levels of eight HR-associated genes were analyzed from formalin-fixed paraffin-embedded core-needle biopsy samples obtained before NACT. A random forest model was built to estimate the weight of each gene expression level and clinicopathological factors. The training set was used to modulate parameters and select the best model. The performance of the final model was evaluated in the validation set.

RESULTS:

A 4-gene (BRCA1, XRCC5, PARP1, and RAD51) scoring system was developed. TNBC patients with a higher score had a nearly fourfold likelihood of achieving pCR to platinum-based NACT compared with patients with a lower score [odds ratio (OR) = 3.878; P < 0.001]. At the cutoff value of - 2.644, the 4-gene scoring system showed high sensitivity in predicting pCR in the breast (93.0%) and pCR in the breast/axilla (91.8%), while at the cutoff value of - 1.969, the 4-gene score showed high specificity for pCR in the breast (85.7%) and pCR in the breast/axilla (80.8%).

CONCLUSION:

The qRT-PCR-based 4-gene score has the potential to predict pCR to platinum-based NACT in TNBC.

• Authors: Ke Zuo, Xiaoying Yuan, Xizi Liang, Xiangjie Sun, Shujin Liu, Philip P Connell, Xingmin Li, Wentao Yang
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 191 Issue 2 Pg. 335-344 (Jan 2022) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 34797456 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Platinum
• DNA

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms
• China
• DNA (therapeutic use)
• Female
• Homologous Recombination
• Humans
• Neoadjuvant Therapy
• Platinum
• Retrospective Studies
• Triple Negative Breast Neoplasms (drug therapy, genetics)