TY - JOUR
T1 - Short preoperative treatment with erlotinib inhibits tumor cell proliferation in hormone receptor-positive breast cancers
AU - Guix, Marta
AU - Granja, Nara De Matos
AU - Meszoely, Ingrid
AU - Adkins, Theresa B.
AU - Wieman, Bobbye M.
AU - Frierson, Kerek E.
AU - Sanchez, Violeta
AU - Sanders, Melinda E.
AU - Grau, Ana M.
AU - Mayer, Ingrid A.
AU - Pestano, Gary
AU - Shyr, Yu
AU - Muthuswamy, Senthil
AU - Calvo, Benjamin
AU - Krontiras, Helen
AU - Krop, Ian E.
AU - Kelley, Mark C.
AU - Arteaga, Carlos L.
PY - 2008/2/20
Y1 - 2008/2/20
N2 - Purpose: To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods: Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results: In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) -positive but not in human epidermal growth factor receptor 2 (HER-2) -positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor-positive cancers. Conclusion: A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2-positive or triple-negative breast cancers.
AB - Purpose: To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods: Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results: In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) -positive but not in human epidermal growth factor receptor 2 (HER-2) -positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor-positive cancers. Conclusion: A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2-positive or triple-negative breast cancers.
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U2 - 10.1200/JCO.2007.13.5939
DO - 10.1200/JCO.2007.13.5939
M3 - Article
C2 - 18180460
AN - SCOPUS:39749085432
SN - 0732-183X
VL - 26
SP - 897
EP - 906
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -