The document summarizes several international guidelines for treating breast cancer, including the St. Gallen, ASCO, NCCN, and AGO guidelines. The St. Gallen guidelines classify risk based on endocrine responsiveness. The NCCN guidelines recommend aromatase inhibitors for 5 years or switching from tamoxifen to an AI after 2-3 years. The ASCO guidelines also recommend aromatase inhibitors for 5 years or switching from tamoxifen to an AI after 2-5 years for no more than 5 years total on the AI.

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