Table 2. Outcomes for each clinical study.
| Reference | ARM1 | ARM2 | ARM3 | Population size (TNBC) | Average age (years) of TNBC patients | Follow up | Outcome | Outcome size | Effect size measures |
|---|---|---|---|---|---|---|---|---|---|
| Bayraktar et al 2012 [10] | Diabetic patients Metformin + Adj chemo + Adj chemo: –anthracycline +/- taxane –single-agent taxane –other |
Diabetic patients Adj chemo alone Adj chemo: –anthracycline +/- taxane –single-agent taxane –other |
Not diabeticpatients |
1,448 patients –ARM1: 63 –ARM2: 67 –ARM3: 1,318 |
ARM1: Median 53 ARM2: Median 51 ARM3: Median 58 |
62 months | 1) Distant metastasis free survival 2) Overall survival 3) Recurrence free survival |
1) ARM1, ARM2, ARM3 0.73 (0.58–0.83), 0.66 (0.52–0.77), 0.60 (0.57–0.62); p = 0.23 1) ARM2 versus ARM1: 1.63 (95% CI: 0.87–3.06) p = 0.13; ARM3 versus ARM1: 1.62 (95%CI: 0.97–2.71) p = 0.06 2) ARM1, ARM2, ARM3: 0.65 (0.51–0.76), 0.64 (0.5–0.75), 0.54 (0.51–0.56); p = 0.38 2) ARM2 versus ARM1: 1.37 (95% CI: 0.78–2.40) p = 0.27; ARM3 versus ARM1: 1.36 (95% CI: 0.87–2.10) p = 0.17 3) ARM1, ARM2, ARM3: 0.67 (0.52–0.79) 0.69 (0.55–0.79), 0.66 (0.63–0.69); p = 0.58 3) ARM2 versus ARM1: 1.22 (95% CI: 0.66–2.28) p = 0.52; ARM3 versus ARM1: 1.28 (95% CI: 0.79–2.08) p = 0.31 |
–Five years estimates rates between the three groups –Hazard ratio |
| Botteri et al 2013 [11] | Beta blockers users | Beta blockers non users | – | 800 patients | ARM1: Mean 62 ARM2: Mean 59 |
ARM1: median 72 months ARM2: median 68 months |
1) Breast Cancer-related events 2) Distant metastasis 3) Breast Cancer death |
1) 13,6% versus 27.9%; p = 0.015 2) 0.32 (95% CI: 0.12–0.90; p = 0.031) 3) 0.42 (95% CI: 0.18–0.97; p = 0.042) |
–Five-year cumulative incidence –Hazard ratio |
| Melhem-Bertrand et al 2011 [12] | Beta blockers + neoadj therapy | Beta blockers non users | – | 1.417 patients –ARM1: 102 –ARM2: 1311 |
ARM1: Mean 47.5 ARM2: Mean 55 |
ARM1: Median 55 months ARM2: Median 63 months |
1) Recurrence free survival 2) Overall survival |
1) 0.30; 95% CI: 0.10–0.87; p = 0.027 2) 0.35; 95% CI: 0.12–1.00; p = 0.05 |
Hazard ratio |
| Spera et al 2017 1 [13] | Beta blockers users | Beta blockers non users | – | 1144 patients –ARM1: 152 –ARM2: 991 |
ARM1: Median 60 ARM2: Median 53 |
Median: 25.1 months | 1) Progression free survival 2) Overall survival |
1) 0.52; 95%CI: 0.34–0.80; p = 0.002 2) 0.87; 95%CI: 0.58–1.31; p = 0.504 |
Hazard ratio |
| Spera et al 2017 - 2 [13] | Beta blockers users | Beta blockers non users | – | 35 patients | – | – | 1) Relapse free survival 2) Overall survival |
1) 0.69; 95%CI: 0.35–1.34; p = 0.269 2) 0.73; 95%CI: 0.35–1.48; p = 0.384 |
Hazard ratio |
| Chan et al 2017 [14] | Tetramyolibdate | – | – | 36 patients | – | Median 6.3 years | Event free survival | Stage II/III patients 90% (95% CI: 78%–100%) Stage IV patients: 69% (95% CI: 49%–96%) |
Two-year event free rate |
| Hasegawa et al 2015 [15] |
Zoledronic acid + Neoadj chemotherapy
Chemotherapy: Four cycles of FEC100 every 3 weeks followed by 12 cycles of paclitaxel at 80 mg/m2 |
Chemotherapy alone Chemotherapy: Four cycles of FEC100 every 3 weeks followed by 12 cycles of paclitaxel at 80 mg/m2 |
– | 34 patients | – | – | Pathological complete response rates | ARM1: 6/17(35.3%) CI: 12.6–58.0; ARM2: 2/17(11.8%) CI: 0.0–27.1; p = 0.112 | Pathological complete response rates |
| Ishikawa et al 2017 [16] | Zoledronic acid + Neoadj chemotherapy Chemotherapy: Four cycles of FEC100 followed by paclitaxel |
Chemotherapy alone Chemotherapy: Four cycles of FEC100 followed by paclitaxel |
– | 34 patients | – | – | Three years disease free survival | ARM1: 94.1%; ARM2: 70.6%; p = 0.077 | Percentage |
| Retsky et al 2012 [17] |
Ketorolac + Chemotherapy |
Chemotherapy alone |
– | Not specified | – | 27.3 months | Disease free survival | Far superior disease-free survival in the first few years after surgery (no data shown) | – |
| Chow et al 2013 [18] |
Celecoxib (200mg) + Neoadj chemo: Chemotherapy: Four cycles of FEC followed by four cycles of docetaxel |
– | – | 2 patients | – | – | 1) Pathological complete response 2) Near Pathological complete response |
1) 0% 2) 50% |
Percentage |
| Shiao et al 2017 [19] | Antiplatelet users + Possible chemotherapy | Not antiplatelet users + Possible chemotherapy | – | 222 patients –ARM1 65 –ARM2 157 |
ARM1: Median 55 ARM2: Median 50 |
ARM1: Median: 41.3 ARM2: Median 40.9 |
1) Five years Disease free survival 2) Five years Overall survival 3) Five years Distant metastasis rate |
1) ARM1: 80.4%; ARM2: 62.3%; 0.503 (0.261–0.970) p = 0.04 2) ARM1: 77.2%; ARM2: 69%;0.652 (0.343–1.239) p = 0.192 3) ARM1: 8.8%; ARM2: 31.9%; 0.310 (0.132–0.729) p = 0.007 |
–Percentage –Hazard ratio |
| Williams et al 2018 [20] | Aspirin users + Possible chemotherapy | Not aspirin users + Possible chemotherapy | – | 147 patients –ARM1: 33 –ARM2: 114 |
– | – | 1) Overall survival 2) Disease free survival |
No specific outcome for TNBC comparing ARM1 versus ARM2 | Hazard ratio |
| Pierga et al 2010 [21] |
Celecoxib + Chemotherapy
Chemotherapy: Eight cycles of EC-D |
Chemotherapy Chemotherapy: Eight cycles of EC-D |
– | 78 patients –ARM1: 44 –ARM2: 34 |
– | – | Pathological complete response | 29.5% (95% CI: 19.7%–40.9%) | Pathological complete response rates |
| Tsubamoto et al 2014 [22] |
Itraconazole + Chemotherapy Chemotherapy : docetaxel, carboplatin, and gemcitabine, vinorelbine, bevacizumab |
– | – | 13 patients | Median: 45 | – | 1) Response rates 2) Progression free survival 3) Overall survival |
1) 62% (95% CI: 35%–88%) 2) 10.8 months (95% CI: 7.6–15.3 months) 3) 20.4 months (95% CI: 13.1–41.4 months) |
Pathological complete response rates |
| Wang et al 2015 [23] |
Esomeprazole low dose (80mg) + chemotherapy
Chemotherapy: Docetaxel followed by cisplatin |
Esomeprazole high dose (100mg) + chemotherapy
Chemotherapy: Docetaxel followed by cisplatin |
Chemotherapy Docetaxel followed by cisplatin |
15 patients –ARM1: 2 –ARM2: 6 –ARM3: 7 |
– | – | Time to progression | 1) 10.7 (ARM1+ARM2) and 5.8 months (ARM3); p = 0.011 | Median time |
| Nanda et al 2016 [24] |
Mifepristone (300mg) + Paclitaxel
|
Mifepristone (300mg) + Paclitaxel
|
Placebo | 4 patients –No information on treatments |
– | – | Treatment response | Three patients have partial response, and one patient complete response | – |
| Lacerda et al 2014 [25] | Statins + Postmastectomy radiation | Postmastectomy radiation | – | –ARM1: 16 –ARM2: 86 |
– | Median: 2.5 years | 3 years Risk of locoregional recurrence | No specific outcome for TNBC | – |
| Shaitelman et al 2017 [26] | Statin users | Statin users (patients with lipid/cholesterol values) | Not statin users | -ARM1: 293 -ARM2: 576 |
– | Median: 75.1 months | ARM1 versus ARM3 1)Recurrence 2)BCa Death ARM2 versus ARM3 3)Recurrence 4)BCa Death |
1) 0.82 (95% CI: 0.57–1.16) 2) 0.70 (95% CI: 0.47–1.03) 3) 0.60 (95% CI: 0.36–1.03) 4) 0.51 (95% CI: 0.28–0.93) |
Relative risk |