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ASCO recommendations and NCCN treatment guidelines are generated by expert consensus using a more rigorous process than the St. Gallen guidelines
ASCO guidelines are based on evidence from relevant publications, conference presentations, and additional data requested from pharmaceutical companies; greater weight is given to published randomised trials 1
All NCCN guideline recommendations are weighted by level of clinical evidence and degree of panel consensus reached through a continuous review and feedback process 2
ASCO and NCCN guidelines are highly detailed and prescriptive
St. Gallen Breast Cancer Guidelines 2007 Update
St. Gallen – Endocrine Responsiveness “Practical” Clinical Subgroups ER and PR absent ER and PR low/int and/or any of these Both receptors high levels
No No No No No Chemo only options Chemo adds to hormonal Chemo doesn’t work Absent Endocrine- responsiveness Uncertain Sure
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
St. Gallen 2007 Breast Cancer Guidelines: Endocrine Therapy for PMW
Supports initial adjuvant AI use in those taking SSRI antidepression medication (due to potential TAM interactions), high-risk patients, or those with HER2+ disease
Prefers switch from TAM to an AI after 2-3 y vs TAM for 5 y
Strongly endorses extended adjuvant AI therapy for patients at increased risk of recurrence (ie, node-positive)
Total optimal duration of adjuvant endocrine therapy is 5-10 y
PMW = postmenopausal women; SSRI = selective serotonin reuptake inhibitor. Goldhirsh et al. Ann Oncol. 2007;18:1133.
NCCN Clinical Practice Guidelines for Breast Cancer 2008 Update
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
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.
ASCO Guidelines for Use of Adjuvant AIs in PMW With HR+ Breast Cancer
An AI (ANA or LET) may substitute for TAM as initial adjuvant therapy to reduce the risk of recurrence
Those currently on TAM may consider switching to an AI after 2-5 years of TAM therapy
Women who switch to an AI may continue this therapy for 2-3 more years, but no longer than 5 years
Treatment with an AI for >5 y has not been studied and should only be done in the context of a clinical trial
HR+ = hormone receptor – positive; ANA = anastrozole; LET = letrozole. Winer et al. J Clin Oncol. 2005;23:619.
ASCO Guidelines for Use of Adjuvant AIs in PMW With HR+ Breast Cancer (cont’d)
There are no data to recommend taking TAM after an AI
In addition, women who develop invasive HR+ breast cancer while taking TAM for prevention, and women who cannot take TAM because of high risk of severe side effects or who had to stop TAM because of severe side effects, might be advised to consider using an AI
It is not known whether the AIs can be used interchangeably
Therefore, using the agent with the most data relevant to each individual clinical setting is favoured
NICE Assessment on Hormonal Therapies for Early Breast Cancer: Key Conclusions
Relative to TAM, AIs improve clinical outcomes when used within their licensed indications as primary adjuvant treatment, in unplanned switching, or as extended adjuvant treatment
AIs are cost-effective when individually compared with T A M
In extended adjuvant treatment, letrozole is cost-effective compared with placebo/no treatment
NICE = National Institute for Health and Clinical Excellence (UK).
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
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