Research article

Serum biomarker profiles and response to neoadjuvant chemotherapy for locally advanced breast cancer

Brian M Nolen¹ , Jeffrey R Marks² , Shlomo Ta'san³ , Alex Rand³ , The Minh Luong⁴ , Yun Wang⁴ , Kimberly Blackwell^5,6 and Anna E Lokshin^1,7,8,9

¹  University of Pittsburgh Cancer Institute, Hillman Cancer Center, Suite 1.19d, 5117 Centre Avenue, Pittsburgh, PA 15213, USA

²  Department of Surgery, Duke University Medical Center, Box 3873 Med Ctr Durham, NC 27710, USA

³  Department of Mathematical Sciences, Carnegie Mellon University, Wean Hall, Room 6113, Pittsburgh, PA 15213-3890, USA

⁴  Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, 130 Desoto Street, 311 Parran Hall, Pittsburgh, PA 15261, USA

⁵  Department of Radiation Oncology, Duke University Medical Center, Box 3893 Med Ctr Durham, NC 27710, USA

⁶  Department of Medicine, Duke University Medical Center, Box 3893 Med Ctr Durham, NC 27710, USA

⁷  Department of Medicine, School of Medicine, University of Pittsburgh, 1218 Scaife Hall 3550 Terrace Street, Pittsburgh, PA 15213, USA

⁸  Department of Pathology, University of Pittsburgh, S-417 BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA

⁹  Department of Obstetrics and Gynecology RS, University of Pittsburgh, 300 Halket Street Pittsburgh, PA 15213, USA

author email corresponding author email

Breast Cancer Research 2008, 10:R45doi:10.1186/bcr2096

Published:	12 May 2008

Abstract

Introduction

Neoadjuvant chemotherapy has become the standard of care for the diverse population of women diagnosed with locally advanced breast cancer. Serum biomarker levels are increasingly being investigated for their ability to predict therapy response and aid in the development of individualized treatment regimens. Multianalyte profiles may offer greater predictive power for neoadjuvant treatment response than the individual biomarkers currently in use.

Methods

Serum samples were collected from 44 patients enrolled in a phase I–II, open-label study of liposomal doxorubicin and paclitaxel in combination with whole breast hyperthermia for the neoadjuvant treatment of locally advanced breast cancer (stage IIB or stage III). Samples were collected prior to each of four rounds of treatment and prior to definitive surgery. Samples were assayed by Luminex assay for 55 serum biomarkers, including cancer antigens, growth/angiogenic factors, apoptosis-related molecules, metastasis-related molecules, adhesion molecules, adipokines, cytokines, chemokines, hormones, and other proteins.

Results

Biomarker levels were compared retrospectively with clinical and pathologic treatment responses. Univariate analysis of the data identified several groups of biomarkers that differed significantly among treatment outcome groups early in the course of neoadjuvant chemotherapy. Multivariate statistical analysis revealed multibiomarker panels that could differentiate between treatment response groups with high sensitivity and specificity.

Conclusion

We demonstrate here that serum biomarker profiles may offer predictive power concerning treatment response and outcome in the neoadjuvant setting. The continued development of these findings will be of considerable clinical utility in the design of treatment regimens for individual breast cancer patients.

Trial registration

#NCT00346229.