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


CONCLUSIONS
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.


BACKGROUND
#NCT00346229.
Nolen
Brian M
BM
University of Pittsburgh Cancer Institute, Hillman Cancer Center, Suite 1,19d, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
Marks
Jeffrey R
JR
Ta'san
Shlomo
S
Rand
Alex
A
Luong
The Minh
TM
Wang
Yun
Y
Blackwell
Kimberly
K
Lokshin
Anna E
AE
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000097:blood* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004317:Doxorubicin; D017239:Paclitaxel