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. 2018 Jun;25(6):595-605.
doi: 10.1530/ERC-17-0495. Epub 2018 Mar 29.

Single drug biomarker prediction for ER- breast cancer outcome from chemotherapy

Yong-Zi Chen  1   2 , Youngchul Kim  1 , Hatem H Soliman  3   4 , GuoGuang Ying  2 , Jae K Lee  5   4
Affiliations

Single drug biomarker prediction for ER- breast cancer outcome from chemotherapy

Yong-Zi Chen et al. Endocr Relat Cancer. 2018 Jun.

Abstract

ER-negative breast cancer includes most aggressive subtypes of breast cancer such as triple negative (TN) breast cancer. Excluded from hormonal and targeted therapies effectively used for other subtypes of breast cancer, standard chemotherapy is one of the primary treatment options for these patients. However, as ER- patients have shown highly heterogeneous responses to different chemotherapies, it has been difficult to select most beneficial chemotherapy treatments for them. In this study, we have simultaneously developed single drug biomarker models for four standard chemotherapy agents: paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses and survival of ER- breast cancer patients treated with combination chemotherapies. We then flexibly combined these individual drug biomarkers for predicting patient outcomes of two independent cohorts of ER- breast cancer patients who were treated with different drug combinations of neoadjuvant chemotherapy. These individual and combined drug biomarker models significantly predicted chemotherapy response for 197 ER- patients in the Hatzis cohort (AUC = 0.637, P = 0.002) and 69 ER- patients in the Hess cohort (AUC = 0.635, P = 0.056). The prediction was also significant for the TN subgroup of both cohorts (AUC = 0.60, 0.72, P = 0.043, 0.009). In survival analysis, our predicted responder patients showed significantly improved survival with a >17 months longer median PFS than the predicted non-responder patients for both ER- and TN subgroups (log-rank test P-value = 0.018 and 0.044). This flexible prediction capability based on single drug biomarkers may allow us to even select new drug combinations most beneficial to individual patients with ER- breast cancer.

Keywords: biomarker; chemotherapy; estrogen receptor; gene expression.

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Figures

Figure 1
Figure 1
Schematic overview of biomarkers discovery and evaluation.
Figure 2
Figure 2
Chemotherapy response evaluation of single and combined drug models for the TN group in the Hess and Hatzis cohorts, respectively. (A) Paclitaxel, 5-fluorouracil, doxorubicin, cyclophosphamide and combined model evaluation for TN group in the Hess cohort, (B) paclitaxel, doxorubicin and combined model evaluation for TN group in the Hatzis cohort.
Figure 3
Figure 3
Disease-free survival time (DFS) for the ER− and TN groups of patients in the Hatzis cohort: (A) ER− group, (B) TN group.
See this image and copyright information in PMC

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