Breast Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Breast Cancer, including details on symptoms, genetics, screening, treatment, information. | ||||||||
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The nuclear transcription factor kappaB/bcl-2 pathway correlates with pathologic complete response to doxorubicin-based neoadjuvant chemotherapy in human breast cancer.Buchholz TA, Garg AK, Chakravarti N, Aggarwal BB, Esteva FJ, Kuerer HM, Singletary SE, Hortobagyi GN, Pusztai L, Cristofanilli M, Sahin AA Department of Radiation Oncology, Breast Medical Oncology, Surgical Oncology, and Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA. tbuchhol@mdanderson.org PURPOSE: Molecular factors involved in apoptosis may affect breast cancer response to chemotherapy. Herein, we studied the nuclear factor kappaB (NF-kappaB)/bcl-2 pathway to determine whether or not activation of this antiapoptotic pathway was associated with a poor response of human breast cancer to anthracycline-based neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: We studied 82 human breast cancer samples from patients treated with neoadjuvant doxorubicin-based chemotherapy and studied whether or not nuclear location of the transcription factor NF-kappaB was associated with expression of bcl-2 and bax and whether or not expression of these proteins correlated with chemotherapy response. Protein expression was measured with immunohistochemical staining. A dedicated breast cancer pathologist who was unaware of the clinical outcome data dichotomized the slides as positive or negative based on the presence or absence of cytoplasmic staining for bcl-2 and bax or nuclear staining for NF-kappaB. RESULTS: Sixty-one percent of the tumors were positive for bcl-2, 85% were positive for bax, and 16% were positive for NF-kappaB. All bcl-2-positive tumors were also bax positive (P < 0.0001) and all NF-kappaB-positive tumors were both bcl-2 positive (P = 0.001) and bax positive (P = 0.113). Eleven of the 82 patients (13%) had a pathologic complete response (pCR) to chemotherapy. Patients with positive staining tumors for any of the markers less commonly achieved a pCR to chemotherapy than those with negative tumor staining. The pCR rates were NF-kappaB positive 0% (0 of 13) versus NF-kappaB negative 13% (11 of 69; P = 0.130); bcl-2 positive 4% (2 of 49) versus bcl-2 negative 27% (9 of 33; P = 0.004); and bax positive 6% (4 of 69) versus bax negative 58% (7 of 12; P < 0.001). CONCLUSION: We conclude that nuclear localization of NF-kappaB correlates with bcl-2 and bax expression and that the NF-kappaB/bcl-2 pathway may be associated with a poor response to neoadjuvant doxorubicin-based chemotherapy. Published 2 December 2005 in Clin Cancer Res, 11(23): 8398-402.
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