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2 乳癌診療指引 106 : : stage II neoadjuvant C/T DCIS page LCIS 3.Oncotype or Symphony gene (Endopredict ICT Mammoprint Pam50) test is optional examination for ambiguous patients. :4. Total mastectomy=simple mastectomy LCIS Stage IA T1N0M0 Stage IB T1N1miM0 page 3. Oncotype or Symphony gene (Endopredict ICT Mammoprint Pam50 )test is optional examination for ambiguous patients T1N0 ER + PR + H/T RT 7.Hormonal therapy: Tamoxifen 5-10 ;AI Total mastectomy=simple mastectomy Stage IIA 3. Oncotype or Symphony gene (Endopredict ICT Mammoprint Pam50 )test is optional examination for ambiguous patients. 8. Total mastectomy=simple mastectomy Stage IIIA ConsiderHerceptin(LN negative) (concider Herceptin for N0) 3. Oncotype or Symphony gene test is optional examination for ambiguous patients. 5. Total mastectomy=simple mastectomy Stage Her-2(+)-> Herceptin Her-2(+)-> anti HER-2 therapy cliniacl trial 3.Oncotype or Symphony gene test is optional examination for ambiguous patients. 4.Anti -HER-2 therapy 癌症診療指引108

3 乳癌診療指引共識1-1 DCIS TisN0M0 ER/PR/Her-2 1. Partial mastectomy SLNB + whole breast radiation therapy 2. Total mastectomy + SLNB reconstruction Adjuvant treatment Tamoxifen for 5 years ER + or uncertain Risk reduction for contralateral breast cancer(optional) AI may also be considered in menopausal women 癌症診療指引109

4 乳癌診療指引共識2-2 core needle biopsy Excision considered LCIS without other cancer Tamoxifen 5 years LCIS DCIS Guideline for DICS ER/PR/Her-2 Initial biopsy was surgical biopsy Invasive breast cancer Guideline for invasive cancer 癌症診療指引110

5 乳癌診療指引共識3-3 Stage IA T1N0M0 Stage IB T1N1miM0 ( HBsAg Anti-HCV test optional) X ER/PR/Her-2 optional optional optional optional optional ER + and/orpr + or unknown Partial mastectomy + ALND or SLNB R/T* Total mastectomy + ALND or SLNB Reconstruction ER - and PR - T 0.5cm 0.5 T 1.0cm 1 T 2.0cm T 0.5cm 0.5 T 1.0cm 1 T 2.0cm NCCN-2013.V2 Stage I 1. Stage I & II favorable histology include tubular and colloid. NCCN guideline 2. Clinical trial is always an option of treatment. 3. Oncotype or Endopredict ICT Mammoprint Pam50 test is optional examination for ambiguous patients. 4. Herceptin 5. Carrier ( HBsAg Anti-HCV test) 6. RT*: Whole breast radiotheray(wbrt) or Partial breast radiotherapy(pbrt), PBRT : ; 70 T1N0 ER + PR + H/T RT 7. ( HBsAg Anti-HCV test optional) 8. Hormonal therapy: Tamoxifen 5-10 ;AI Total mastectomy=simple mastectomy Hormonal Therapy 1.Hormonal therapy C/T 2.Her-2(+) Consider Herceptin* No adjuvant Tx 1. C/T 2. Her-2(+)-> Consider Herceptin* 1. C/T 2. Her-2(+)-> Suggest Herceptin* 3 / : ~ : ~ X (optional) 4~5 / : X (optional) 5 癌症診療指引111

6 乳癌診療指引共識4-4 Stage IIA T0 N1 M0 T1 N1 M0 T2 N0 M0 or Stage IIB T2N1M0 T3N0M0 ( HBsAg Anti-HCV test optional) X ER/PR/Her-2 optional optional optional optional optional ( Neoadjuvant therapy) Neoadjuvant C/T Target therapy *MRM->R/T criteria: 1. Tumor > 5cm 2. LN positive 4 3. LN 1-3 strongly consider optional 4. Margin positive Partial mastectomy + ALND or SLNB + R/T* Total mastectomy + ALND or SLNB reconstruction R/T* ER - and PR - ER + and/ or PR + or unknown 1. C/T+H/T 2. Her-2 (+) Consider Herceptin* 1. Chemotherapy 2. Her-2 (+) Consider Herceptin* NCCN-2013.V2 Stage II 1. Stage I & II favorable histology include tubular and colloid. NCCN guideline 2. Clinical trial is always an option of treatment. 3. Oncotype or Endopredict ICT Mammoprint Pam50test is optional examination for ambiguous patients. 4. * Herceptin 5. Carrier ( HBsAg Anti-HCV test) 6. RT*: Whole breast radiotheray(wbrt) or Partial breast radiotherapy(pbrt), PBRT :RT*: 7. ( HBsAg Anti-HCV test optional) 8. Total mastectomy=simple mastectomy 3 / : ~ : ~ X (optional) 4~5 / : X (optional) 5 癌症診療指引112

7 乳癌診療指引共識5-5 Stage IIIA T0N2M0 T1N2M0 T2N2M0 T3N1M0 T3N2M0 Stage IIIB T4N0M0 T4N1M0 T4N2M0 Stage IIIC Any TN3M0 ( HBsAg Anti-HCV test) X ER/PR/Her-2 (Alternative) (Alternative) PET scan optional ( Neoadjuvant therapy) Neoadjuvant C/T Target therapy and/or ER + and/or PR + or nknown Partial mastectomy + ALND or SLNB + R/T* Total mastectomy + ALND or SLNB + R/T reconstruction ER - and PR - 1. Stage I & II favorable histology include tubular and colloid. NCCN guideline 2. Clinical trial is always an option of treatment. 3. RT*: 4. Abdomen sono or abdomen CT Alternative 5. Total mastectomy=simple mastectomy 1.C/T+H/T 2.Her-2 (+) Anti-Her-2 therapy (consider Herceptin for N0) 1.C/T 2.Her-2 (+) Anti-Her-2 therapy (consider Herceptin for N0) 3 / : ~ : ~ X (optional) 4~5 / : X (optional) 5 癌症診療指引113

8 乳癌診療指引共識6-6 Stage IV ( HBsAg Anti-HCV test) X Stage IV Any T Any N M1 ER/PR/Her-2 (Alternative) (Alternative) Systemic chemotherapy Hormonal therapy Radiotherapy Her-2(+)-> anti HER-2 therapy Best supportive care Palliative surgery and other forms local treatment if needs Clinical trial / : : X (optional) 癌症診療指引114 PET scan optional 1. tage I & II favorable histology include tubular and colloid. NCCN guideline 2. Clinical trial is always an option of treatment. 3. Abdomen sono or abdomen CT Alternative 4. Anti -HER-2 therapy

9 乳癌診療指引參考文獻 1. NCCN Clinical Practice in Oncology:Breast Cancer V NCCN Clinical Practice in Oncology:Breast Cancer V Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, CA CancerJ Clin 2010;60: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365: Edge SB, Byrd DR, Compton CC, et al., eds. AJCC Cancer Staging Manual, 7th Edition. New York: Springer; Allred DC, Carlson RW, Berry DA, et al. NCCN Task Force Report:Estrogen Receptor and Progesterone Receptor Testing in Breast Cancer by Immunohistochemistry. J Natl Compr Canc Netw 2009;7 Suppl 6: Dybdal N, Leiberman G, Anderson S, et al. Determination of HER2 gene amplification by fluorescence in situ hybridization and concordance 8. with the clinical trials immunohistochemical assay in women with metastatic breast cancer evaluated for treatment with trastuzumab. Breast Cancer Res Treat 2005;93: Chuba PJ, Hamre MR, Yap J, et al. Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ: analysis of surveillance, epidemiology, and end results data. J Clin Oncol 2005;23: Anderson BO, Calhoun KE, Rosen EL. Evolving concepts in the management of lobular neoplasia. J Natl Compr Canc Netw 2006;4: Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005;97: Vargas C, Kestin L, Go N, et al. Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy. Int J Radiat Oncol Biol Phys 2005;63: 癌症診療指引115

10 癌症診療指引116 Chemotherapy as Primary or Adjuvant Therapy (HER2-POSTIVE) PREFERRED REGIMENS AC followed by Paclitaxel with Trastuzumab mg/m 2 Doxorubicin 60 1 Q3W 4 1 Cyclophosphamide Q3W 4 Followed by Trastuzumab 4 2 mg/kg 1 QW 12 Paclitaxel 80 1 QW 12 Followed by Trastuzumab 2 (6) mg/kg 1 QW (Q3W) 40 (13) AC followed by Paclitaxel with Trastuzumab + Pertuzumab (optional) mg/m 2 Doxorubicin 60 1 Q3W 4 8 Cyclophosphamide Q3W 4 Followed by Trastuzumab 8 6 mg/kg 1 Q3W 17 Pertuzumab* mg 1 Q3W 17 Paclitaxel 80 1, 8, 15 Q3W 4 *Optional

11 AC followed by Paclitaxel with Trastuzumab Dose-dense 癌症診療指引117 mg/m 2 Doxorubicin 60 1 Q2W 4 2 Cyclophosphamide Q2W 4 Followed by Trastuzumab 4 2 mg/kg 1, 8 Q2W 4 Paclitaxel Q2W 4 Followed by Trastuzumab 2 (6) mg/kg 1 QW (Q3W) 44 (14) TCH mg/m 2 Trastuzumab 4 2 mg/kg 1, 8,15 Q3W 6 3 Docetaxel 75 1 Q3W 6 Carboplatin 6 AUC 1 Q3W 6 Followed by Trastuzumab 6 mg/kg 1 Q3W 11 TCH + Pertuzumab (optional) mg/m 2 Trastuzumab 8 6 mg/kg 1 Q3W 17 4 Pertuzumab* mg 1 Q3W 17 Docetaxel 75 1 Q3W 6 Carboplatin 6 AUC 1 Q3W 6 *Optional

12 REGIMENS OTHER 癌症診療指引118 AC followed by Docetaxel with Trastuzumab mg/m 2 Doxorubicin 60 1 Q3W 4 3 Cyclophosphamide Q3W 4 Followed by Trastuzumab 4 2 mg/kg 1, 8, 15 Q3W 4 Docetaxel Q3W 4 Followed by Trastuzumab 6 mg/kg 1 Q3W 13 AC followed by Docetaxel with Trastuzumab + Pertuzumab mg/m 2 Doxorubicin 60 1 Q3W 4 3 Cyclophosphamide Q3W 4 Followed by Trastuzumab 8 6 mg/kg 1 Q3W 17 Pertuzumab* mg 1 Q3W 17 Docetaxel Q3W 4 *Optional Paclitaxel + Trastuzumab mg/m 2 Trastuzumab 4 2 mg/kg 1 QW 12 5 Paclitaxel 80 1 QW 12 Followed by Trastuzumab 2 (6) mg/kg 1 QW (Q3W) 40 (13)

13 + Trastuzumab TC 癌症診療指引119 mg/m 2 Trastuzumab 4 2 (8 6) mg/kg 1, 8, 15 (1) Q3W 4 8 Docetaxel 75 1 Q3W 4 Cyclophosphamide Q3W 4 Followed by Trastuzumab 6 mg/kg 1 Q3W 13 TC + Trastuzumab mg/m 2 Neoadjuvant Therapy 6 Trastuzumab 4 2 (8 6) mg/kg 1, 8, 15 (1) Q3W 4 Pertuzumab mg 1 Q3W 4 Docetaxel Q3W 4 Followed by Adjuvant Therapy Fluorouracil Q3W 3 Epirubicin 90 1 Q3W 3 Cyclophosphamide Q3W 3 Followed by Trastuzumab 6 mg/kg 1 Q3W 17

14 + Trastuzumab TA(E)C 癌症診療指引120 mg/m 2 Docetaxel 75 1 Q3W 6 Doxorubicin 50 1 Q3W 6 Cyclophosphamide Q3W 6 Followed by Trastuzumab 6 mg/kg 1 Q3W Romond EH, Perez EZ, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2 positive breast cancer. N Engl J Med 2005;353: Dang C, Fomier M, Sugarman S, et al. The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER2/neu over expressed/amplified breast cancer. J Clin Oncol. 2008;26(8): Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011;365: Schneeweiss A, Chia S, Hickish T et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracyclinecontaining and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013; 24: Tolaney S, Barry W, Dang C,et al. Adjuvant paclitaxel and trastuzumab for node-negative HER2-positive breast cancer. N Engl J Med 2015;372: Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 2012 Jan;13(1):25-32.

15 8. Jones SE, Collea R, Paul D, et al. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a singlegroup, open-label, phase 2 study. Lancet Oncol 2013;14: NCCN BINV-K 4 of 7. 癌症診療指引121

16 as Primary or Adjuvant Therapy (HER2-NEGATIVE) Chemotherapy 癌症診療指引122 PREFERRED REGIMENS Dose-dense AC followed by Paclitaxel mg/m 2 Doxorubicin 60 1 Q2W 4 1 Cyclophosphamide Q2W 4 Followed by Paclitaxel Q2W 4 Dose-dense AC followed by weekly Paclitaxel mg/m 2 Doxorubicin 60 1 Q2W 4 1 Cyclophosphamide Q2W 4 Followed by Paclitaxel 80 1 QW 12 TC mg/m 2 Docetaxel 75 1 Q3W 4 2 Cyclophosphamide Q3W 4

17 REGIMENS OTHER 癌症診療指引123 Dose-dense AC mg/m 2 Doxorubicin 60 1 Q2W 4 1 Cyclophosphamide Q2W 4 AC mg/m 2 Doxorubicin 60 1 Q3W 4 3 Cyclophosphamide Q3W 4 TAC mg/m 2 Docetaxel Q3W 6 4 Doxorubicin 60 1 Q3W 6 Cyclophosphamide Q3W 6 TEC mg/m 2 Docetaxel 75 1 Q3W 6 15 Epirubicin 75 1 Q3W 6 Cyclophosphamide Q3W 6

18 FAC 癌症診療指引124 mg/m 2 5-FU 500 1, 8 or 1, 4 Q3W 6 5, 6 Doxorubicin 50 1 Q3W 6 Cyclophosphamide Q3W 6 CEF mg/m 2 Cyclophosphamide 500 1, 8 Q3W 6 7 Epirubicin 80 1, 8 Q3W 6 5-FU 500 1, 8 Q3W 6 CMF mg/m 2 Cyclophosphamide Q3W 6 8 Methotrexate 40 1 Q3W 6 5-FU Q3W 6 AC followed by Docetaxel mg/m 2 Doxorubicin 60 1 Q3W 4 9 Cyclophosphamide Q3W 4 Followed by Docetaxel Q3W 4

19 followed by Paclitaxel AC 癌症診療指引125 mg/m 2 Doxorubicin 60 1 Q3W 4 10 Cyclophosphamide Q3W 4 Followed by Paclitaxel Q3W 4 AC followed by weekly Paclitaxel mg/m 2 Doxorubicin 60 1 Q3W 4 10 Cyclophosphamide Q3W 4 Followed by Paclitaxel 80 1 QW 4 EC mg/m 2 Epirubicin Q3W 4 11 Cyclophosphamide Q3W 4 FEC followed by Docetaxel mg/m 2 5-FU Q3W 3 12 Epirubicin Q3W 3 Cyclophosphamide Q3W 3 Followed by Docetaxel Q3W 3

20 followed by weekly Paclitaxel FEC 癌症診療指引126 mg/m 2 5-FU Q3W 4 13 Epirubicin 90 1 Q3W 4 Cyclophosphamide Q3W 4 Followed by 3 Weeks no treatment Followed by Paclitaxel QW 8 FLC mg/m 2 5-FU Q3W 6 Lipo-Doxorubicin Q3W 6 Cyclophosphamide Q3W 6 Cisplatin + Docetaxel (Triple negative) mg/m 2 Cisplatin 60 Docetaxel 60

21 癌症診療指引 Citron ML, Berry DA, Cirrincione C, et al: Randomized Trial of Dose-Dense Versus Conventionally Scheduled and Sequential Versus Concurrent Combination Chemotherapy as Postoperative Adjuvant Treatment of Node-Positive Primary Breast Cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial J Clin Oncol 2003;21: Jones S, Holmes F, O'Shaughnessey J, et al. Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial J Clin Oncol 2009;27: Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 1990;8: Martin, Pienknowski T, Mackey L, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352: Buzdar AU, Kau SW, Smith TL, Hortobagyi GN. Ten-year results of. FAC adjuvant chemotherapy trial in breast cancer. Am J Clin Oncol. 1989;12; Assikis V, Buzdar A, Yang Y, et al. A Phase III Trial of Sequential Adjuvant Chemotherapy for Operable Breast Carcinoma. Final Analysis with 10-Year Follow-Up. Cancer 2003;97: Levine MN, Bramwell VH, Pritchard KI, et al. Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 1998;16: Goldhirsch A, Colleoni M, Coates AS, et al. Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? The International Breast Cancer Study Group (IBCSG). Ann Oncol 1998;9: von Minckwitz G1, Raab G, Caputo A, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol 2005;23(12): Sparano JA, Wang M, Martino S, et al. Weekly Paclitaxel in the Adjuvant Treatment of Breast Cancer. N Engl J Med 2008;258:

22 Cyclophosphamide With Cyclophosphamide, Methotrexate, and Fluorouracil in Node-Positive Breast Cancer. J Clin Oncol 2001;19: Roche H, Fumoleau P, Spielmann M, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol 2006; 24: Martin M, Rodriguez-Lescure A, Ruiz A, et al. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst 2008;100: NCCN [BINV-K 3 of 7]. Breast cancer, version 3, Bayo, J., Prieto, B. and Rivera, F. Comparison of Doctors' and Breast Cancer Patients' Perceptions of Docetaxel, Epirubicin, and Cyclophosphamide (TEC) Toxicity. Breast J 2016; 22: Piccart MJ, Di Leo A, Beauduin M, et al. Phase III Trial Comparing Two Dose Levels of Epirubicin Combined With 11. 癌症診療指引128

23 Endocine Therapy Adjuvant 癌症診療指引129 Anti-estrogen mg/m 2 Tamoxifen mg PO QD 1 Aromatase inhibitor mg/m 2 Exemestane 25 mg PO QD 2 mg/m 2 Anastrozole 1 mg PO QD 3 mg/m 2 Letrozole 2.5 mg PO QD 4 Ovarian supressoion or ablation mg/m 2 Goserelin Acetate 3.6 mg SC 1 Q4W 5 mg/m 2 Leuprolide Acetate 3.75 mg SC 1 Q4W 6

24 癌症診療指引 Product Information: tamoxifen citrate oral tablets, tamoxifen citrate oral tablets. Watson Laboratories (per manufacturer), Corona, CA, Product Information: AROMASIN(R) oral tablets, exemestane oral tablets. Pharmacia & Upjohn Company (per FDA), New York, NY, Product Information: ARIMIDEX(R) oral tablet, anastrozole oral tablet. AstraZeneca Pharmaceuticals LP, Wilmington, DE, Product Information: Femara oral tablets, letrozole oral tablets. Novartis Pharmaceuticals Corporation, East Hanover, NJ, Product Information: ZOLADEX(R) implant 3.6mg, goserelin acetate implant implant 3.6mg. AstraZeneca, Wilmington, DE, Boccardo F, Rubagotti A, Amoroso D, et al: Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breat cancer patients. Cancer Chemother Pharmacol 1999; 43:

25 REGIMENS FOR RECURRENT OR METASTATIC BREAST CANCER CHEMOTHERAPY 癌症診療指引131 HER2-NEGATIVE PREFERRED SINGLE AGENTS Anthacyclins mg/m 2 Doxorubicin Q3W 7 1 mg/m 2 Doxorubicin 20 1 QW 2 mg/m 2 Lipo-Doxorubicin 50 1 Q4W 3 Taxanes mg/m 2 Paclitaxel Q3W 4 mg/m 2 Paclitaxel 80 1 QW 5

26 Antimetabolites 癌症診療指引132 mg/m 2 Capecitabine PO BID 1-14 Q3W 6 6 mg/m 2 Gemcitabine , 8, 15 Q4W 7 Other microtubule inhibitors mg/m 2 Vinorelbine 25 1 QW 8 mg/m 2 Eribulin 1.4 1, 8 Q3W 9 PARP inhibitors mg/m 2 Olaparib 300 mg PO BID

27 SINGLE AGENTS OTHER 癌症診療指引133 mg/m 2 Cyclophosphamide 50 PO QD 1-21 Q4W 10 mg/m 2 Carboplatin 6 AUC 1 Q3W-Q4W 11 mg/m 2 Docetaxel Q3W 6 12, 13 mg/m 2 Docetaxel 35 1, 8, 15, 22, 29, 36 Q8W 14 mg/m 2 Albumin-Paclitaxel 100 or 150 1, 8, 15 Q4W 15, 16 mg/m 2 Albumin-Paclitaxel Q3W 15 mg/m 2 Cisplatin 75 1 Q3W 4 17 mg/m 2 Epirubicin 75 1 Q3W 18

28 Combinations 癌症診療指引134 CAF mg/m 2 Cyclophosphamide 100 PO 1-14 Q4W 19 Doxorubicin 30 1, 8 Q4W 5-FU 500 1, 8 Q4W FAC mg/m 2 5-FU 500 1, 8 or 1, 4 Q3W 20 Doxorubicin 50 1 Q3W Cyclophosphamide Q3W FEC mg/m 2 Cyclophosphamide 400 1, 8 Q4W Epirubicin 50 1, 8 Q4W 5-FU 500 1, 8 Q4W AC mg/m 2 Doxorubicin 60 1 Q3W 8 22 Cyclophosphamide Q3W 8

29 EC 癌症診療指引135 mg/m 2 Epirubicin 75 1 Q3W 6 23 Cyclophosphamide Q3W 6 CMF mg/m 2 Cyclophosphamide 100 PO QD 1-14 Q4W 24 Methotrexate 40 1, 8 Q4W 5-FU 600 1, 8 Q4W Docetaxel + Capecitabine mg/m 2 Docetaxel 75 1 Q3W 6 25 Capecitabine 950 PO BID 1-14 Q3W 6 GT mg/m 2 Paclitaxel Q3W 26 Gemcitabine , 8 Q3W

30 + Carboplatin Gemcitabine 癌症診療指引136 mg/m 2 Gemcitabine , 8 Q3W 27 Carboplatin 2 AUC 1, 8 Q3W Bevacizumab + Paclitaxel mg/m 2 Bevacizumab 10 mg/kg 1, 8 Q4W 28 Paclitaxel 90 1, 8, 15 Q4W HER2-POSATIVE PREFERRED AGENTS mg/m 2 Pertuzumab mg 1 Q3W 29 Trastuzumab 8 6 mg/kg 1 Q3W Docetaxel Q3W mg/m 2 Pertuzumab mg 1 Q3W 30, 31 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) Paclitaxel 175 (80) 1 Q3W (QW)

31 AGENTS OTHER 癌症診療指引137 mg/m 2 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) 31, 32 Paclitaxel Q3W Carboplatin 6 AUC 1 Q3W mg/m 2 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) 31, 33, 34 Paclitaxel 175 (80-90) 1 Q3W (QW) mg/m 2 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) 31, 35, 36 Docetaxel (35) 1, 8, 15 (1) Q3W (QW) mg/m 2 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) 31, 37 Vinorelbine (25) 1, 8 (1) Q3W (QW) mg/m 2 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) 31, 33, 38, 39 Capecitabine Q3W

32 agents for Trastuzumab-exposed HER2-positive disease Preferred 癌症診療指引138 mg/m 2 T-DM1 3.6 mg/kg 1 Q3W 40 Other agents for Trastuzumab-exposed HER2-positive disease mg/m 2 Lapatinib 1250 mg PO QD 1-21 Q3W 41 Capecitabine 1000 PO BID 1-14 Q3W mg/m 2 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) 31, 33, 39, 42 Capecitabine PO BID 1-14 Q3W mg/m 2 Trastuzumab 8 6 (4 2) mg/kg 1 Q3W (QW) 31, 43 Lapatinib 1000 mg PO QD Q3W 1. Chan S, Friendrichs K, Noel D, et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol Aug;17(8): Gasparini G, Dai Fior S, Panizzoni GA, et al. Weekly epirubicin versus doxorubicin as second line therapy in advanced breast cancer. A randomized clinical trial. Am J Clin Oncol Feb;14(1):38-44.

33 O'Brien ME, Wigler N, Inbar M, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal 3. 癌症診療指引139 doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol Mar;15(3): Seidman AD, Tiersten A, Hudis C, et al. Phase II trial of paclitaxel by 3-hour infusion as initial and salvage chemotherapy for metastatic breast cancer. J Clin Oncol 1995;13: Perez EA, Vogel CL, Irwin DH, et al. Multicenter Phase II Trial of Weekly Paclitaxel in Women With Metastatic Breast Cancer. J Clin Oncol 2001;19: Safety and Efficacy of Two Different Doses of Capecitabine in the Treatment of Advanced Breast Cancer in Older Women. J Clin Oncol 2005;23: Seidman AD, Gemcitabine as Single-Agent Therapy in the Management of Advanced Breast Cancer. Oncology (Williston Park)2001;15: Zelek L, Barthier S, Riofrio M, et al. Weekly vinorelbine is an effective palliative regimen after failure with anthracyclines and taxanes in metastatic breast carcinoma. Cancer Nov 1;92(9): Cortes J, O'Shaughnessy J, Loesch D, et al. Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet 2011;377: Licchetta A, Correale P, Migali C, et al. Oral Metronomic Chemo-Hormonal-Therapy of Metastatic Breast Cancer with Cyclophosphamide and Megestrol Acetate. J Chemother 2010;22(3): Isakoff, SJ, Goss PE, et al. (2011). TBCRC009: A multicenter phase II study of cisplatin or carboplatin for metastatic triplenegative breast cancer and evaluation of p63/p73 as a biomarker of response[abstract]. J Clin Oncol 29(15_suppl):Abstract Burris HA, 3rd. Single-agent docetaxel(taxotere) in randomized phase III trials, Semin Oncol 1999;26: Harvey V, Mouridsen H, Semiglazov V, et al. Phase III Trial Comparing Three Doses of Docetaxel for Second-Line Treatment of Advanced Breast Cancer. J Clin Oncol 2006;24(31): Rivera E, Mejia JA, Arun BJ, et al. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer 2008 Apr 1;112(7): Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With

34 Castor Oil Based Paclitaxel in Women With Breast Cancer. J Clin Oncol 2005;23: Polyethylated 癌症診療指引 Gradishar W, Dimitry K, Sergey C, et al. Significantly Longer Progression-Free Survival With nab-paclitaxel Compared With Docetaxel As First-Line Therapy for Metastatic Breast Cancer. J Clin Oncol 2009;27(22): Silver DP, Richardson AL, Eklund AC, et al. Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer. J Clin Oncol 2010;28(7): Bastholt L, Dalmark M, Gjedde SB, et al. Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group. J Clin Oncol 1996;14: Bull JM, Tormey DC, Li SH, et al. A randomized comparative trial of adriamycin versus methotrexate in combination drug therapy. Cancer 1978;41: Hortobagyi GN, Gutterman JU, Blumenschein GR, et al. Combination chemoimmunotherapy of metastatic breast cancer with 5-fluorouracil, adriamycin, cyclophosphamide, and BCG. Cancer 1979;43: Ackland SP, Anton A, Breitibach GP, et al. Dose-Intensive Epirubicin-Based Chemotherapy Is Superior to an Intensive Intravenous Cyclophosphamide, Methotrexate, and Fluorouracil Regimen in Metastatic Breast Cancer: A Randomized Multinational Study. J Clin Oncol 2001;19: Nabholtz JM, Falkson C, Campos D, et al. Docetaxel and Doxorubicin Compared With Doxorubicin and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer: Results of a Randomized, Multicenter, Phase III Trial. J Clin Oncol 2003;21(6): Langley RE, Camichel J, Jones AL, et al. Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute. J Clin Oncol 2005;23: Bonadonna G, Brusamolino E, Valagussa P, et al. Combination Chemotherapy as an Adjuvant Treatment in Operable Breast Cancer. N Engl Med 1976;294: Mavroundis D, Papakotoulas P, Ardavanis A, et al. Randomized phase III trial comparing docetaxel plus epirubicin versus

35 plus capecitabine as first-line treatment in women with advanced breast cancer. Ann Oncol 21:48(2010). docetaxel 癌症診療指引 Albian KS, Nag S, Calderillo-Ruiz G, ey al. Gemcitabine Plus Paclitaxel Versus Paclitaxel Monotherapy in Patients With Metastatic Breast Cancer and Prior Anthracycline Treatment. J Clin Oncol 2008;26(24): O'Shaughnessy J, Schwartzberg LS, Danso MA, et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). [abstract]. J Clin Oncol 2011;29(Supll_15):Abstract Miller K, Wang M, Gralow J, et al. Paclitaxel plus Bevacizumab versus Paclitaxel Alone for Metastatic Breast Cancer. N Engl J Med 2007;357: Baselga J, Cortes J, Kim SB, et al. Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer. N Engl J Med 2012;366: Phase II study of pertuzumab, trastuzumab, and weekly paclitaxel in patients with HER2-overexpressing metastatic breast cancer [abstract]. Cancer Research 2012;72:Abstract P Leyland-Jones B, Gelmon K, Ayoub JP, et al. Pharmacokinetics, Safety, and Efficacy of Trastuzumab Administered Every Three Weeks in Combination With Paclitaxel. J Clin Oncol 2003;21: Perez EA, Suman VJ, Rowland KM, et al. Two Concurrent Phase II Trials of Paclitaxel/Carboplatin/Trastuzumab (Weekly or Every-3-Week Schedule) as First-Line Therapy in Women with HER2-Overexpressing Metastatic Breast Cancer: NCCTG Study Clin Breast Cancer 2005;6: Slamon DJ, Leyland-Jones B, Shak S, et al. Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2. N Engl J Med 2001;344: Seidman A, Berry DA, Cirrincione C, et al. Randomized Phase III Trial of Weekly Compared With Every-3-Weeks Paclitaxel for Metastatic Breast Cancer, With Trastuzumab for all HER-2 Overexpressors and Random Assignment to Trastuzumab or Not in HER-2 Nonoverexpressors: Final Results of Cancer and Leukemia Group B Protocol J Clin Oncol 2008;26: Marty M, Cognetti F, Maraninchi D, et al. Randomized Phase II Trial of the Efficacy and Safety of Trastuzumab Combined With Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2 Positive Metastatic Breast Cancer Administered As First-Line Treatment: The M77001 Study Group. J Clin Oncol 2005;23:

36 Esteva FJ, Valero V, Booser D, et al. Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER 癌症診療指引142 Overexpressing Metastatic Breast Cancer. J Clin Oncol 2002;20: Burstein HJ, Keshaviah A, Baron AD, et al. Trastuzumab plus vinorelbine or taxane chemotherapy for HER2-overexpressing metastatic breast cancer: The trastuzumab and vinorelbine or taxane study. Cancer 2007;110: von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab Beyond Progression in Human Epidermal Growth Factor Receptor 2 Positive Advanced Breast Cancer: A German Breast Group 26/Breast International Group Study. J Clin Oncol 2009;27: Cobleigh MA, Vogel CL, Tripathy D, et al. Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease. J Clin Oncol 1999;17: Verma S, Miles D, Gianni L, et al. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer [Supplementary appendix available online]. N Engl J Med 2012;367: Geyer C, Forster J, Lindquist D, et al. Lapatinib plus Capecitabine for HER2-Positive Advanced Breast Cancer. N Engl J Med 2006;355: Bartsch R, Wenzel C, Altorjai G, et al. Capecitabine and Trastuzumab in Heavily Pretreated Metastatic Breast Cancer. J Clin Oncol 2007;25: Blackwell KL, Burstein H, et al. Randomized Study of Lapatinib Alone or in Combination With Trastuzumab in Women With ErbB2-Positive, Trastuzumab-Refractory Metastatic Breast Cancer. J Clin Oncol 2010;28(7):

37 THERAPY REGIMENS FOR RECURRENT OR METASTATIC BREAST CANCER ENDOCRINE 癌症診療指引143 Premenopausal SERM mg/m 2 Tamoxifen mg PO QD 1 Ovarian ablation or suppression mg/m 2 Goserelin Acetate 3.6 mg SC Q4W 5 mg/m 2 Leuprolide Acetate 3.75 mg SC Q4W 6 Postmenopausal Aromatase inhibitor mg/m 2 Exemestane 25 mg PO QD 2 mg/m 2 Anastrozole 1 mg PO QD 3

38 mg/m2 癌症診療指引144 Letrozole 2.5 mg PO QD 4 SERD mg/m 2 Fulvestrant 500 IM Q4W 7 CDK4/6 inhibitor+ai (for Her2-negative) mg/m 2 Palbociclib 125 mg PO QD 1-21 Q4W Letrozole 2.5 mg PO QD mg/m 2 Palbociclib 125 mg PO QD 1-21 Q4W Anastrozole 1 mg PO QD mg/m 2 Palbociclib 125 mg PO QD 1-21 Q4W Exemestane 25 mg PO QD

39 inhibitor + SERD CDK4/6 癌症診療指引145 mg/m 2 Palbociclib 125 mg PO QD 1-21 Q4W Fulvestrant 500 IM 1, 15 1 Q4W 1. Product Information: tamoxifen citrate oral tablets, tamoxifen citrate oral tablets. Watson Laboratories (per manufacturer), Corona, CA, Product Information: AROMASIN(R) oral tablets, exemestane oral tablets. Pharmacia & Upjohn Company (per FDA), New York, NY, Product Information: ARIMIDEX(R) oral tablet, anastrozole oral tablet. AstraZeneca Pharmaceuticals LP, Wilmington, DE, Product Information: Femara oral tablets, letrozole oral tablets. Novartis Pharmaceuticals Corporation, East Hanover, NJ, Product Information: ZOLADEX(R) implant 3.6mg, goserelin acetate implant implant 3.6mg. AstraZeneca, Wilmington, DE, Boccardo F, Rubagotti A, Amoroso D, et al: Endocrinological and clinical evaluation of two depot formulations of leuprolide acetate in pre- and perimenopausal breat cancer patients. Cancer Chemother Pharmacol 1999; 43: Rita S. Mehta, M.D., William E. Barlow, Ph.D.,et al.combination Anastrozole and Fulvestrant in Metastatic Breast Cancer.

40 乳癌放射治療共識 1. ( ) / 1. / ( Gy / ) ( Gy / ) ( Gy / ) / / 10-14Gy / ~2.0Gy 2.6~2.7Gy Gy 2. / Gy / / 10-14Gy / (IORT) 20~21Gy / 1 癌症診療指引146

41 乳癌放射治療共識 1. NCCN clinical practice guidelines in oncology-breast cancer. version International Commission on Radiation Units and Measurements. ICRU Report No 50: Prescribing, Recording and Reporting Photon Beam Therapy. Bethesda, MD: ICRU Publications International Commission on Radiation Units and Measurements. ICRU Report No 62: Prescribing, Recording and Reporting Photon Beam Therapy Supplement to ICRU Report 50. Bethesda, MD: ICRU Publications 癌症診療指引147

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