乳腺癌的輔助治療從臨床指南走向臨床實踐討論

1、Treatment of Early-Stage Breast Cancer: Considerations Enough? ADJUVANT BREAST CANCER DECISION = PUZZLE ! Guidelines (NIH, NCCN, St-Gallen ) Personal experience and local policy Industry advertising Literature (individual studies, review) Reimbursement conditions， insurance policy Adjuvant online Wi

2、th so many parameters to consider, how do we approach treatment? Develop Clinical Practice Guidelines Defined as “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances” Institute of Medicine Committee to Adv

3、ise the Public Health Service on Clinical Practice Guidelines, 1990. TREATMENT GUIDELINES FOR ADJUVANT THERAPY OF BREAST CANCER Aim : to enhance individual clinical decision-making Evidence : from clinical trials / metaanalysis (= Average treatment effects) Opinion of breast cancer experts is import

4、ant Inter-Guideline Comparison As expected, significant agreement in scientific content Eg, in 9 guidelines on NSCLC included in the analysis, the concordance was 80% (80-98%) Heterogeneity reflects Different development groups and intended focus Differences in diagnostic and treatment approach by c

5、ountry Different resources available Different uptake of the new approaches Different level of patient involvement in the decision making process Pentheroudakis et al. Ann Oncol. 2008;19:2067-2078. Patient Examples: Key Points Local / national guidelines: Faster adaptation of clinical trial data Sim

6、ilar recommendations of evidence- based regimens More practical International guidelines: More general Slower/longer process of integrating newer regimens CASE 1 40 year old, premenopausal woman Infiltrating ductal carcinoma Tumor 0.5 cm 0/10 positive lymph nodes Grade 1 ER+，PR+. HER+ 輔助治療方案? NCCN 2

7、010 ESMO ST.GALLEN 適應癥 雌激素或孕激素雌激素或孕激素受體陽性受體陽性的浸潤性乳腺癌患者，不論年齡的浸潤性乳腺癌患者，不論年齡 、淋巴結狀態(tài)或是否應用了輔助化療，都應、淋巴結狀態(tài)或是否應用了輔助化療，都應考慮輔助內分考慮輔助內分 泌治療。泌治療。 CASE 1 40 year old, premenopausal woman Infiltrating ductal carcinoma Tumor 0.5 cm 0/10 positive lymph nodes Grade 1 ER+，PR+. HER+ 輔助治療方案? TAM CASE 2 Presentation for

8、 second opinion: 46 years Large regional breast center: tumor excision + sentinel node biopsy right side + breast reduction both sides Invasive ductal breast cancer: pT2 (3 cm), pN0 (sn) Grade 2 ， ，R0 ER +, PR+, HER2 0 Premenopausal 風險評價與治療選擇風險評價與治療選擇 CASE 2.: Adjuvant! Online Results https:/ CASE 2

9、.: Adjuvant! Online Results 46 y.o., pT2 (3cm), pN0, Grade 2, R0, ER/PR+, HER2- 2nd generation regimen + tamoxifen Risk of relapse at 10 yrs with no additional therapy = 37% Risk of death at 10 yrs with no additional therapy = 17% DFSOS Proportional Risk reduction (relapse) Proportional Risk reducti

10、on (mortality) Hormonal therapy 40%32% Chemotherapy50%44% Combined therapy60%62% Evolution of Chemotherapy in BC CMF Milan AC B-15 FEC50 ICCG = = CEF MA.5 FAC GEICAM TAC BCIRG 001 TC US9735 AC-P C9344 B-28 AC-T E1199 AC-Pw E1199 AC2w-P2w C9741 FEC100 FASG05 FEC-Pw G9906 FEC-T PACS01 ESMO 46 y.o., pT

11、2 (3cm), pN0, Grade 2, R0, ER/PR+, HER2- ST GALLEN 46 y.o., pT2 (3cm), pN0, Grade 2, R0, ER/PR+, HER2- St gallen ST GALLEN NCCN ESMO 化療方案化療方案 Patient M.F.: Guideline Recommendations 46 y.o., pT2 (3cm), pN0, Grade 2, R0, ER/PR+, HER2- Risk CategoryTreatmentPreferred Chemotherapy ESMOIntermediateET al

12、one or CT ET ACMF, CEF, ACT, TAC, FECT, FEC100, ATCMF St. GallenIntermediateET (consider + CT) Specific regimens not listed NCCN-Consider 21-gene assay or ET CT TAC, TC, ACP, AC CT = chemotherapy; ET = endocrine therapy CASE 2 Therapy recommendation: Recommendation: NNBC-3 trial ESMO: 3x FEC 3x Doce

13、taxel; US: TAC; CHINA ? A-BASED Radiotherapy right breast Endocrine therapy (TAM) CASE 3 40 year old, premenopausal woman Infiltrating ductal carcinoma Tumor 2.1 cm 0/10 positive lymph nodes Grade 2 ER and PgR-negative HER2 2+, FISH positive LVEF = 52% HECEPTIN? CT regimen？ ESMO ST GALLEN NCCN CASE

14、3 40 y., 2.1cm, LN -ve, Grade 2, ER and PR -ve, HER2 + Risk Category TreatmentPreferred Chemotherapy Trastuzumab ESMOMCT + HACMF, CEF, ACT, TAC, FECT, FEC100, ATCMF 3-weekly x 1 y not concurrent with anthra St. GallenMCT + H No specific regimen ACPH, sequential HERA approach, TCH NCCN-CT + HTCH, ACP

15、H, THFEC, ACTH CT = chemotherapy; ET = endocrine therapy; H=trastuzumab CASE 3 40 year old, premenopausal woman Infiltrating ductal carcinoma Tumor 2.1 cm 0/10 positive lymph nodes Grade 2 ER and PgR-negative HER2 2+, FISH positive LVEF = 52% HECEPTIN. ACPH, TCH CASE 4 43 year old, premenopausal wom

16、an Infiltrating ductal carcinoma Tumor 3 cm 2/12 positive lymph nodes Grade 2 ER 9/12, PR 6/12 HER2 2+, TAM OR OTHER? ST GALLEN ESMO NCCN ASCO CASE 4 43 year old, premenopausal woman Infiltrating ductal carcinoma Tumor 3 cm 2/12 positive lymph nodes Grade 2 ER 9/12, PR 6/12 HER2 2+, TAM OR TAM + OS(

17、 ? YEARS) CASE 5 40歲 3CM,G1,N- 5%浸潤性導管癌，95%DCIS ER+，PR+. HER+ 輔助治療方案? 輔助治療方案? TAM? CT? HECEPTIN? Endocrine- responsiveness C H E M O T H E R A P Y ADJUVANT CHEMOTHERAPY REGIMENS IN 2010 Standard efficacyStandard efficacy Superior efficacy CMF x 6FEC x 6AC x 4 P x 4 (or WP x 12) AC x 4 D x 4 FEC x 3

18、D x 3 (PACS01) A x 3 D x 3 CMF x 3 (BIG 02-98) A(E)C x 4 A(C) x 4 CMF x 3 (TC x 4) TAC x 6 (BCIRG001) Dose-dense AC x 4 P x 4 Regimens with decreased cardiac risk ! D,T : docetaxel P : paclitaxel SELECTION OF ADJUVANT CHEMOTHERAPY REGIMENS : ACCORDING TO THE ENDOCRINE-RESPONSIVENESS AND THE RISK OF

19、THE TUMOR Endocrine-responsiveness AbsentUncertainHigh low Intermediate High FEC A(C) CMF AC CMF Endocrine therapy Anthracyclines + taxane (e.g., FEC x 3 D x 3) FEC A(C) CMF Anthracycline + taxane Risk ADD Endocrine therapy Important Questions That Remain Do guidelines work and to what extent should

20、 they reflect multidisciplinary collaboration? Do clinicians follow the published guidelines? Is this country-specific? Are we reducing physician freedom of choice? General guidelines vs “specific, one question answering” guidelines/recommendations? How does reimbursement fit it? Best treatment vs b

21、est available treatment Impact of todays guidelines on future development Should we design trials in areas where level of evidence is low? Conclusions Guidelines using an evidence-based approach have great value for standardizing treatment decision making Limitation continues to be lack of flexibili

22、ty and lack of information about impact on practice Envision the future to include the integration of increasingly more complex patient- and treatment- specific characteristics for a more individualized approach CASE 2 Presentation for second opinion: 46 years Large regional breast center: tumor excision + sentinel node biopsy right side + breast reduction both sides Invasive ductal breast cancer: pT2 (3 cm), pN0 (sn) Grade 2 ， ，R0 ER +, PR+, HER