Table 1.
Treatment | Comparator | Measure of Effect | Reference |
---|---|---|---|
Early Stage Breast Cancer | |||
Endocrine Therapy in Postmenopausal Women | |||
5 year tamoxifen | Placebo | 15 year breast cancer mortality RR 0.70 (95% CI 0.64–0.75), p < 0.00001 | [24] |
5 year total therapy (tamoxifen → AI) | 5 year tamoxifen | 10 year breast cancer mortality RR 0.85 (95% CI 0.75–0.96), p = 0.015 | [9] |
5 year AI | 5 year tamoxifen | 10 year breast cancer mortality RR 0.85 (95% CI 0.75–0.96), p = 0.009 | [9] |
5 year total therapy (AI → tamoxifen) | 5 year AI | 8 year DFS HR 1.06 (95% CI 0.91–1.23), p = 0.48 | [25] |
10 year extended therapy (tamoxifen) | 5 year tamoxifen | Benefit highest after 10 year, e.g., 10–14 year breast cancer mortality RR 0.71 (95% CI 0.58–0.88), p = 0.01 | [6] |
10 year extended therapy (AI) | 5 year AI → 5 year placebo | 5 year DFS HR 0.66 (95% CI 0.48–0.91), p = 0.01 | [26] |
Endocrine Therapy in Premenopausal Women | |||
5 year tamoxifen | Placebo | 15 year breast cancer mortality RR 0.70 (95% CI 0.64–0.75), p < 0.00001 | [24] |
5 year tamoxifen + LHRH agonist | 5 year tamoxifen | Benefit in high-risk, e.g., 8 year DFS HR 0.76 (95% CI 0.60–0.97) in those receiving adjuvant chemotherapy | [8] |
5 year AI + LHRH agonist | 5 year tamoxifen | Benefit in high-risk, e.g., 8 year DFS HR 0.68 (95% CI 0.53–0.88) in those receiving adjuvant chemotherapy | [8] |
Chemotherapy and Other Systemic Therapy | |||
Anthracycline + taxane regimen | Anthracycline w/o taxane regimen | 8 y breast cancer mortality RR 0.86 (95% CI 0.79–0.93) | [27] |
Bisphosphonate | No bisphosphonate | In postmenopausal women, OS HR 0.77 (95% CI 0.66-0.90), p = 0.001; no benefit seen in premenopausal women | [28] |
Advanced Breast Cancer | |||
Endocrine + Targeted Therapy in Postmenopausal Women | |||
AI + CDK4/6 inhibitor | AI + placebo | See Table 2 | |
Fulvestrant + CDK4/6 inhibitor | Fulvestrant + placebo | See Table 2 | |
Fulvestrant + alpelisib | Fulvestrant + placebo | In patients with PIK3CAmut, median PFS 11.0 vs. 5.7 month, HR 0.65 (95% CI 0.50–0.85), p < 0.001 | [20] |
Exemestane + everolimus | Exemestane + placebo | Median PFS 6.9 vs. 2.8 month, HR 0.43 (95% CI 0.35–0.54), p < 0.001 | [21] |
Endocrine + Targeted Therapy in Premenopausal Women | |||
As a general principle, many targeted strategies with AI or fulvestrant backbone above can be combined with LHRH agonist for premenopausal women | |||
Tamoxifen + ribociclib | Tamoxifen + placebo | See Table 2 | |
Chemotherapy and Other Systemic Therapy | |||
Sequential mono-chemotherapy | NA | e.g., taxane, anthracycline, capecitabine, eribulin, vinorelbine, gemcitabine | [29] |
Combination chemotherapy | NA | Consider in patients with visceral crisis | [29] |
PARP inhibitor | Physician’s choice chemotherapy | In patients with germline BRCA1/2mut, median PFS 7.0 vs. 4.2 mth, HR 0.58 (95% CI 0.43–0.80), p < 0.001 | [30] |
Denosumab | Bisphosphonate * | Skeletal-related event RR 0.78 (95% CI 0.72–0.85), p < 0.001 | [28] |
AI: aromatase inhibitor; AC: doxorubicin (Adriamycin) and cyclophosphamide; BRCA1/2: breast cancer gene 1/2; CDK4/6: cyclin-dependent kinase 4/6; HR: hazard ratio; LHRH: luteinising hormone-releasing hormone; OR: odds ratio; RR: risk ratio; DFS: disease-free survival; PFS: progression-free survival; OS: overall survival; mth: month. * For patients with bone metastases.