1. Understanding Breast Cancer Guidelines Rowan Chlebowski, MD, PhD

5. St. Gallen Breast Cancer Guidelines 2007 Update

7. Preferred and Alternative Treatment Regimens Tam = tamoxifen; AI = aromatase inhibitor; OFS= ovarian function suppression; GnRH=gonadotropin-releasing hormone; N = node; CT=chemotherapy Goldhirsh et al. Ann Oncol. 2007;18:1133. Combinations of cyclophosphamide, 5-fluorouracil, and an anthracycline Sequence of anthracycline and cyclophosphamide followed by paclitaxel or docetaxel Cannot be viewed as a standard treatment in women with a primary tumor <1 cm and no axillary node involvement Commencement with or after CT equally acceptable GnRH only (if pregnancy planned) AI + OFS (if Tam contraindicated) Tam (5 y) ± OFS with GnRH Premenopausal Chemotherapy Trastuzumab Tam (5 y) -> AI (not prospective; in presence of N+ disease) Initial AI (HER2+ or high risk) Accepted alternative Tam (5 y) Tam (2-3 y) -> AI Endocrine Therapy Preferred Postmenopausal

9. NCCN Clinical Practice Guidelines for Breast Cancer 2008 Update

10. 2008 NCCN Breast Cancer Treatment Guidelines: Adjuvant Endocrine Therapy pT1, pT2, or pT3 and pN0 or pN1mi (≤2 mm axillary node metastasis) Node positive (≥1 metastases >2 mm to ≥1 ipsilateral axillary lymph nodes) Tumor ≤ 0.5 cm or Microinvasive or Tumor 0.6-1.0 cm, well differentiated, no unfavorable features Tumor 0.6-1.0 cm, moderate/poorly differentiated or unfavorable features Tumor >1 cm pN0 pN1mi Adjuvant endocrine therapy ± adjuvant chemotherapy Adjuvant endocrine therapy Consider adjuvant endocrine therapy No adjuvant therapy Adapted with permission from 2008 NCCN guidelines. Adjuvant endocrine therapy + adjuvant chemotherapy + trastuzumab if HER2+ Consider 21-gene RT-PCR assay Low score (<18) Intermediate Score (18-30) Not done High score (≥31) HR positive disease

11. NCCN Breast Cancer Guidelines Adjuvant Endocrine Therapy Postmenopausal AI for 5 y (category 1) Tamoxifen for 2-3 y Tamoxifen to 4.5-6 y AI to complete 5 y (category 1) or longer (category 2B) AI for 5 y (category 1) Women with contra-indication to AIs, who decline AIs or who are intolerant of the As, tamoxifen for 5 y (category 1) AI: Aromatase Inhibitor National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology – Breast Cancer. V.2.2008. At: www.nccn.org.

12. ASCO Technology Assessment Recommendations 2004 Update

15. Regional Guidelines

17. AGO Recommendations 2007: Adjuvant Endocrine Therapy for PMW *Up to 30 months. AGO Guidelines. http://www.ago-online.de/download/00GuidelinesEnglish.pdf. + B 2b EXE for 5 y + B 2b ANA for 3 y + D 4 LET for 5 y – long TAM-free interval* ++ B 1b LET for 5 y – N+ disease + B 1b LET for 5 y – overall AI after 5 y of TAM Extended Adjuvant + B 1b ANA or LET for 5 y ++ B 1b EXE or ANA after 2-3 y of TAM ++ A 1a TAM for 5 y (vs 2 or 1 y) AGO Grade of Recommendation Oxford Level of Evidence Adjuvant

18. AGO Recommendations 2008: Adjuvant Endocrine Therapy for PMW *Up to 30 months. LOE = level of evidence; GR = grade of recommendation. AGO Guidelines available at: http://www.ago-online.com/download/00GuidelinesEnglish.pdf (Guidelines Breast 2008 Version 1.1). Extended Adjuvant + D 4 LET for 5 y – long TAM-free interval* + B 2b ANA for 3 y + B 2b EXE for 5 y + A 1b LET for 5 y – overall ++ B 1b LET for 5 y – N+ disease AI after 5 y of TAM ++ B 1b ANA or LET for 5 y ++ B 1b EXE or ANA after 2-3 y of TAM ++ A 1a TAM for 5 y (vs 2 or 1 y) AGO Grade of Recommendation Oxford Level of Evidence Adjuvant