Table 1.
Characteristics of the studies included in the present analysis.
| Trial | Year | Setting | Subtype | Class of Drug | Drug/regimen tested | Men enrollment per inclusion criteria | N pts enrolled | N men enrolled |
|---|---|---|---|---|---|---|---|---|
|
Nabholtz et al. North American Multicenter Randomized Trial [14] |
2000 | Metastatic | HR+/HER2- | ET | Anastrozole vs.Tamoxifen | No | 353 | NA |
| Mouridsen et al. Phase III study of the International Letrozole Breast Cancer Group [15] |
2001 | Metastatic | HR+/HER-2- | ET | Letrozole vs. Tamoxifen | No | 907 | NA |
| Slamon et al. Use of Chemotherapy plus a Monoclonal Antibody against HER2 for Metastatic Breast Cancer That Overexpresses HER2 [16] |
2001 | Metastatic | HER-2+ | Anti-HER2 (no ADC) | CT +/H | No | 469 | NA |
| Baum et al. ATAC [17] |
2002 | Early/Adjuvant | HR+/HER2-HER2+ | ET | Anastrozole vs. Tamoxifen | No | 9366 | NA |
| Bear et al. NSABP PROTOCOL B-27 [18] |
2003 | Early | HR+/HER-2-TNBC | CT | AC-T-surgery vs. AC-Surgery vs. AC-Surgery-T | No | 2411 | NA |
| Citron et al. Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741 [19] |
2003 | Early/adjuvant | HR+/HER-2-TNBC | CT | CT dose dense vs. conventionally scheduled CT | No | 2005 | NA |
| Piccart-Gebhart HERA [20] |
2005 | Early/adjuvant | HER-2+ | Anti-HER2 (no ADC) | H 1 y vs. 2y vs. Observation | No | 5081 | NA |
| Cataliotti et al. PROACT [21] |
2006 | Early/neoadjuvant | HR+/HER-2- | ET | Anastrozole vs. tamoxifen | No | 451 | NA |
| Jones et al. US Oncology Research Trial 9735 [22] |
2006 | Early/Adjuvant | HR+/HER-2-TNBC | CT | AC vs. TC | No | 1016 | NA |
| Paridaens et al. Phase III Study Comparing Exemestane With Tamoxifen As First-Line Hormonal Treatment of Metastatic Breast Cancer in Postmenopausal Women: The European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group [23] |
2008 | Metastatic | HR+/HER-2-TNBC | ET | Exemestane vs. Tamoxifen | No | 371 | NA |
| Gianni et al. NOAH [24] |
2010 | Early/Neoadjuvant | HER-2+ | Anti-HER2 (no ADC) | CT ± H | No | 235 | NA |
| Leo et al. CONFIRM [25] |
2010 | Metastatic | HR+/HER-2- | ET | Fulvestrant 250 mg vs. Fulvestrant 500 mg | No | 736 | NA |
| Cortés et al. EMBRACE [26] |
2011 | Metastatic | HR+/HER-2-HER-2+ TNBC |
CT | Eribulin vs. TPC | No | 762 | NA |
| Slamon et al. Adjuvant H in HER2-Positive Breast Cancer [27] |
2011 | Early/adjuvant | HER-2+ | Anti-HER2 (no ADC) | AC -T + H vs. AC-T vs. T + Carbolatin + H | No | 3222 | NA |
| Baselga et al. BOLERO-2 [28] |
2012 | Metastatic | HR+/HER2- | PI3K/AKT/mTORi | Everolimus + exemestane vs. Exemestane + Placebo | No | 724 | NA |
| Davies et al. ATLAS [29] |
2012 | Early/Adjuvant | HR+/HER2- | ET | Tamoxifen | No | 12894 | NA |
| Swain et al. CLEOPATRA [30] |
2012 | Metastatic | HER2+ | Anti-HER2 (no ADC) | T + H + P vs. T + H + Placebo | Yes | 808 | 2 |
| Verma et al. EMILIA [31] |
2012 | Metastatic | HER-2+ | ADC | TDM-1 vs. lapatinib + Capecitabine | Yes | 991 | 5 |
| Iwata et al. A randomized, double-blind, controlled study of exemestane versus anastrozole for the first-line treatment of postmenopausal Japanese women with hormone-receptor-positive advanced breast cancer. [32] . |
2013 | Metastatic | HR+/HER2-HER2+ | ET | Exemestane vs. Anastrozole | No | 298 | NA |
| Nitz et al. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc [33] |
2014 | Early/Adjuvant | HR+/HER-2-HER-2+ TNBC |
CT | EC vs. FEC | No | 2012 | NA |
| Del Mastro et al. GIM-2 [34] |
2015 | Early/adjuvant | HR+/HER-2-HER-2+ TNBC |
CT | CT dose dense vs. CT standard interval | No | 2091 | NA |
| Kaufman et al. E7389-G000–301 [35] |
2015 | Metastatic | HR+/HER-2-HER-2+ TNBC |
CT | Eribulin vs. Capeciitabine | No | 1102 | NA |
| Pivot et al. CEREBEL [36] |
2015 | Metastatic | HER2+ | Anti-HER2 (no ADC) | Lapatinib-Capecitabine vs. H-Capecitabine | No | 540 | NA |
| Rugo et al. CALGB 40502/NCCTG N063H (Alliance) [37] |
2015 | Metastatic | HR+/HER2-HER2+ TNBC |
CT | Paclitaxel vs. Nab-Paclitaxel | Yes | 799 | 11 |
| Blum et al. The ABC Trials: USOR 06–090, NSABP B-46-I/USOR 07132, and NSABP B-49 [38] |
2016 | Early/Adjuvant | HR+/HER2-TNBC | CT | TC vs. AC | No | 4242 | NA |
| Chan et al. EXTENET [39] |
2016 | Early/Adjuvant | HER-2+ | Anti-HER2 (no ADC) | Neratinib vs. Placebo | No | 2840 | NA |
| Cristofanilli et al. PALOMA 3 [40] |
2016 | Metastatic | HR+/HER-2- | CDK4/6i | Fulvestrant + Palbociclib/placebo | No | 521 | NA |
| Finn et al. PALOMA-2 [41] |
2016 | Metastatic | HR+/HER2- | CDK4/6i | Palbociclib + Letrozole vs.Placebo + Letrozole | No | 666 | NA |
| Hortobagyi et al. MONALEESA-2 [42] |
2016 | Metastatic | HR+/HER-2- | CDK4/6i | Letrozole + Ribociclib/Placebo | No | 668 | NA |
| Robertson et al. FALCON [43] |
2016 | Metastatic | HR+/HER-2- | ET | Fulvestrant vs. Anastrozole | No | 462 | NA |
| Goetz et al. MONARCH 3 [44] |
2017 | Metastatic | HR+/HER-2- | CDK4/6i | AI + Abemaciclib/Placebo | No | 493 | NA |
| Robson et al. OlympiAD [45] |
2017 | Metastatic | HR+/HER-2-TNBC | PARP-i | Olaparib vs. TPC | Yes | 302 | 7 |
| Sledge et al. MONARCH-2 [46] |
2017 | Metastatic | HR+/HER-2- | CDK4/6i | Fulvestrant + Abemaciclib/placebo | No | 669 | NA |
| Von Minckwitz et al. APHINITY [47] |
2017 | Early/Adjuvant | HER2+ | Anti-HER2 (no ADC) | CT + H + P vs. CT + H + Placebo |
Yes | 4805 | 11 |
| Litton et al. EMBRACA [48] |
2018 | Metastatic | HR+/HER-2-TNBC | PARP-i | Talazoparib vs. CT | Yes | 431 | 7 |
| Loibl et al. BRIGHTNESS [49] |
2018 | Early/neoadjuvant | TNBC | CT | Paclitaxel ± Carboplatin/Placebo -Veliparib/Placebo | No | 634 | NA |
| Schmid et al. IMpassion130 [50] |
2018 | Metastatic | TNBC | ICI | Nab-paclitaxel ± Atezolizumab | Yes | 902 | 4 |
| Slamon et al. MONALEESA-3 [51] |
2018 | Metastatic | HR+/HER-2- | CDK4/6i | Fulvestrant + Ribociclib/Placebo | Yes | 726 | 0 |
| Tripathy et al. MONALEESA-7 [52] |
2018 | Metastatic | HR+/HER-2- | CDK4/6i | Tamoxifen or AI + LHRHa + Ribocilib/Placebo | No | 672 | NA |
| Tutt et al. TNT [53] |
2018 | Metastatic | TNBC | CT | Carboplatin vs. T | No | 376 | NA |
| Andrè et al. SOLAR-1 [54] |
2019 | Metastatic | HER-2+ | PI3K/AKT/mTORi | Fulvestrant + Alpelisib/Placebo | Yes | 572 | 1 |
| von Minckwitz et al. KATHERINE [55] |
2019 | Early/Adjuvant | HER-2+ | ADC | TDM-1 vs. H | No | 1486 | NA |
| Cortes et al. KEYNOTE-355 [56] |
2020 | Metastatic | TNBC | ICI | CT + Pembrolizumab/Placebo | Yes | 847 | 0 |
| Johnston et al. MONARCH-E [57] |
2020 | Early/Adjuvant | HR+/HER-2- | CDK4/6i | ET ± Abemaciclib | Yes | 5637 | 36 |
| Murthy et al. HER2CLIMB [58] |
2020 | Metastatic | HER-2+ | Anti-HER2 (no ADC) | H + Capecitabine + Tucatinib/Placebo | Yes | 612 | 5 |
| Schmid et al. KEYNOTE-522 [56] |
2020 | Early/neoadjuvant | TNBC | ICI | CT + Pembrolizumab/Placebo | Yes | 1174 | 1 |
| Bardia et al. ASCENT [59] |
2021 | Metastatic | TNBC | ADC | SG vs. CT | Yes | 468 | 2 |
| Tutt et al. OLYMPIA [60] |
2021 | Early/Adjuvant | HR+/HER-2-TNBC | PARP-i | Olaparib vs. Placebo | Yes | 1836 | 6 |
| Bidard et al. EMERALD [61] |
2022 | Metastatic | HR+/HER-2- | ET | Elacestrant vs. standard ET | Yes | 705 | 7 |
| Cortés et al. DESTINY-Breast03 [62] |
2022 | Metastatic | HER2+ | ADC | TDX-d vs. TDM-1 | Yes | 524 | 2 |
| Rugo et al. TROPICs-02 [63] |
2022 | Metastatic | HR+/HER-2-TNBC | ADC | Sacituzumab-Govitecan vs. TPC | Yes | 543 | 5 |
Abbreviations: AC: doxorubicin and cyclophosphamide; AI: aromatase inhibitor; ADC: antibody drug conjugates; CT: Chemotherapy; EC: epirubicine and cyclophosphamide; ET: endocrine therapy; FEC: 5-fluorouracil, epidoxorubicin and cyclophosphamide; H: Trastuzumab; HR: hormone receptor positive; N= Number; P: Pertuzumab; T: Docetaxel; TC: Docetaxel and cyclophosphamide; TDM-1: Trastuzuamb-emtansine; TDX-d: Trastuzumab-deruxtecan; TNBC: triple negative breast cancer; TPC: treatment of physician's choice.