personalized therapy for breast cancer gene expression ：乳腺癌基因表达的个性化治疗

Developing Personalized Therapy Breast Cancer: Gene Expression Signatures Alex E. Denes , M.D. Lake of the Ozarks September 26, 2010 Outcomes of Adjuvant Chemotherapy in Breast Cancer Walgren et al. JCO 2005;23:7342-7349 Objectives Case: Chemotherapy or hormonal therapy Who should receive adjuvant chemotherapy? The birth of gene-expression signatures: Intrinsic breast cancer subtypes Gene Expression Signatures under development 70-gene Signature (MammaPrint) 21-gene Signature ( Oncotype DX) Clinical and economic impact of gene expression profiling Clinical Case 62 y/o WF with newly diagnosed IDC R breast MMG / Ultrasound 1.2 x 1.2 cm mass at 10 oclock + surrounding microcalcifications + several suspicious axillary LNs s/p modified radical mastectomy Surgical Path 2.1 cm lesion consisting of IDC mixed with DCIS; intermediate grade; 11 (-) LNs; ER+/PR+/HER-2-; T2N0M0 What is her risk of recurrence? What is her risk of death? What is your recommendation for adjuvant therapy? Tamoxifen Aromatase Inhibitor Hormonal therapy + chemotherapy How else can we classify these tumors? Who Should Receive Adjuvant Chemotherapy? 65% of women with invasive breast cancer have LN(-) disease Adjuvant chemotherapy improves DFS and OS in pre- and postmenopausal women low risk for recurrence Based on oncotype results her oncologist recommended adjuvant aromatase inhibitor x 5 years without chemotherapy Conclusions Gene signatures augment current clinicopathological variables in assessing risk of recurrence Gene expression profiles may be both prognostic and predictive for patients with early breast cancer NCCN guidelines suggest that Oncotype DX is an option for risk evaluation in 0.6-1 cm tumors with unfavorable characteristics or in 1 cm LN-, ER+/HER2 negative tumors NCCN guidelines include Oncotype DX testing in the treatment-decision pathway for node-negative and micrometastatic disease Adapted from NCCN Practice Guidelines in Oncology v.1.2010. Tumor 0.6-1.0 cm, moderately or poorly differentiated, intermediate or high grade, or vascular invasion Tumor 1 cm with favorable or unfavorable pathologic features Consider Oncotyp e DX Hormone receptor-positive, HER2-negative disease pT1, pT2, or pT3 and pN1mi No test RS 18 RS 18- 30 RS 31 Adjuvant endocrine therapy adjuvant chemotherapy Adjuvant endocrine therapy endocrine therapy adjuvant chemotherapy Adjuvant Adjuvant endocrine therapy + adjuvant chemotherapy RS, Recurrence Score result 40 TamoxifenTamoxifen ChemotherapyChemotherapy Anth, Taxane, Anth, Taxane, PlatimunPlatimun Postmenopausal Postmenopausal Women with HR+ Women with HR+ breast Cancerbreast Cancer Aromatase Aromatase Inhibito