Letrozole Is More Effective Neoadjuvant Endocrine Therapy Than Tamoxifen for ErbB-1– and/or ErbB-2–Positive, Estrogen Receptor–Positive Primary Breast Cancer: Evidence From a Phase III Randomized Trial

American Society of Clinical Oncology (ASCO) - Tập 19 Số 18 - Trang 3808-3816 - 2001
Matthew J. Ellis1, Andrew Coop2,3,1,4,5,6,7,8, Baljit Singh2,3,1,4,5,6,7,8, L. Mauriac2,3,1,4,5,6,7,8, Antonio Llombert-Cussac2,3,1,4,5,6,7,8, F. Jänicke2,3,1,4,5,6,7,8, William R. Miller2,3,1,4,5,6,7,8, Dean B. Evans2,3,1,4,5,6,7,8, Margaret Dugan2,3,1,4,5,6,7,8, C. Brady2,3,1,4,5,6,7,8, Erhard Quebe‐Fehling2,3,1,4,5,6,7,8, M. Borgs2,3,1,4,5,6,7,8
1From the Duke University Comprehensive Cancer Center, Durham, NC; Lombardi Cancer Center, Washington DC; Institut Bergonié, Bordeaux Cedex, France; Instituto Valenciano de Oncologia, Valencia, Spain; Universitaets Frauen-und Poliklinik UKE, Hamburg, Germany; Breast Research Unit, Western General Hospital, Edinburgh, United Kingdom; Novartis Pharma AG, Basel, Switzerland; and Novartis Pharmaceuticals, East Hanover, NJ.
2Duke University Breast Cancer Program, Box 3446, The Morris Building, Rm 25149F,
3Duke University Medical Center, Durham, NC 27710
4Instituto Valenciano de Oncologia, Valen-cia, Spain;
5Novartis Pharma AG, Basel, Switzerland; and
6Novartis Pharmaceuticals, East Hanover, NJ
7Universitaets Frauen-und Poliklinik UKE, Hamburg, Ger-many; Breast Research Unit,
8Western General Hospital, Edinburgh, United Kingdom

Tóm tắt

PURPOSE: Expression of ErbB-1 and ErbB-2 (epidermal growth factor receptor and HER2/neu) in breast cancer may cause tamoxifen resistance, but not all studies concur. Additionally, the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown. A neoadjuvant study for primary breast cancer that randomized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospectively. PATIENTS AND METHODS: Postmenopausal patients with estrogen– and/or progesterone receptor–positive (ER+ and/or PgR+) primary breast cancer ineligible for breast-conserving surgery were randomly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study. Immunohistochemistry (IHC) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score. ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria. RESULTS: For study biopsy-confirmed ER+ and/or PgR+ cases that received letrozole, 60% responded and 48% underwent successful breast-conserving surgery. The response to tamoxifen was inferior (41%, P = .004), and fewer patients underwent breast conservation (36%, P = .036). Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and/or ErbB-2 and ER (88% v 21%, P = .0004). CONCLUSION: ER+, ErbB-1+, and/or ErbB-2+ primary breast cancer responded well to letrozole, but responses to tamoxifen were infrequent. This suggests that ErbB-1 and ErbB-2 signaling through ER is ligand-dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy.

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Tài liệu tham khảo

10.1177/107327480000700607

10.1200/JCO.2000.18.22.3758

10.1200/JCO.2000.18.22.3748

10.1016/S0959-8049(00)00239-2

10.1200/JCO.2001.19.10.2596

10.1016/S0305-7372(97)90037-2

10.1007/BF00689675

10.1038/bjc.1992.22

10.1200/JCO.1997.15.7.2518

10.1016/0378-1119(94)00534-Y

10.1038/bjc.1995.497

10.1200/JCO.1996.14.10.2702

Lipton A, Ali SM, Leitzel K, et al: Elevated serum Her-2/neu predicts decreased response to hormone therapy in metastatic breast cancer. Proc Am Soc Clin Oncol 19: 1a,2000 (abstr 274)

Elledge RM, Green S, Ciocca D, et al: HER-2 expression and response to tamoxifen in estrogen receptor- positive breast cancer: A Southwest Oncology Group study. Clin Cancer Res 4: 7,1998-12,

10.1200/JCO.2000.18.20.3471

Newby JC, Johnston SR, Smith IE, et al: Expression of epidermal growth factor receptor and c-2 during the development of tamoxifen resistance in human breast cancer. Clin Cancer Res 3: 1643,1997-1651, erbB

Esteban JM, Ahn C, Battifora H, et al: Quantitative immunohistochemical assay for hormonal receptors: Technical aspects and biological significance. J Cell Biochem Suppl 19: 138,1994-145,

Press MF, Pike MC, Chazin VR, et al: Her-2/neu expression in node-negative breast cancer: Direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease. Cancer Res 53: 4960,1993-4970,

10.1056/NEJM198811103191902

Allred DC, Harvey JM, Berardo M, et al: Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11: 155,1998-168,

10.1200/JCO.1999.17.7.1983

Clark GM, McGuire WL: Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol 15: 20,1988-25,

10.1056/NEJM198312013092240

10.1016/S0140-6736(97)11423-4

Ellis M, Singh B, Miller WR, et al: Letrozole (Femara) is a more effective inhibitor of estrogen activity than tamoxifen: Evidence from a randomized phase III trial of 4 months preoperative endocrine therapy for postmenopausal women with primary invasive breast cancer. Proc Am Soc Clin Oncol 20: 416a,2001 (abstr 1661)

Benz CC, Scott GK, Sarup JC, et al: Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat 24: 85,1993-95,

Lee H, Jiang F, Wang Q, et al: MEKK1 activation of human estrogen receptor alpha and stimulation of the agonistic activity of 4-hydroxytamoxifen in endometrial and ovarian cancer cells. Mol Endocrinol 14: 1882,2000-1896,

10.1007/978-1-4757-3147-7_4

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American Society of Clinical Oncology (ASCO)

Tập 19 Số 18

3808-3816

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