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. 2021 Aug 20;13:6537–6566. doi: 10.2147/CMAR.S300869

Table 1.

Studies Included in the Systematic Literature Review

Study [Ref] Population in Prognostic Analysis Sample Size (N) Age (in Years) HR
+
(%)		 ER
+
(%)		 PR
+
(%)		 HER2–
(%)		 Category
by HR+/HER2–
Status (%)		 Description of BC
Arciero et al
(2017)22 		HR+/HER2– subgroup 106,036 Age at diagnosis, Mean (SD), White: 62.4 (13.6); and African American:58.9 (13.5) 100 NR NR 100 ≥80 Stage III and IV
Aversa et al
(2014)61 		Overall sample=488
Analysis conducted in subgroup of patients with CNS metastases (n=115)		 488 Age at first BC diagnosis, Median (range): 51 (22–83)
Age at first metastatic recurrence, median
(range): 55 (24–85)		 67.8 66.2 49.7 68 50–79 mBC with patients starting first-line chemotherapy
Ayala de la
Pena et al
(2017) (CA)62 		Overall study population 265 Median (range): 59 (19–95) 76 NR NR 73 50–79 mBC
Beije et al
(2016)77 		Overall study population 154 Age at inclusion, Median (range) ET: 67 (37–88); and CT: 61 (33–85) NR 83.7 NR 100 ≥80 mBC
Bertaut et al
(2015)88 		Overall study population 232 Age at diagnosis, Mean (SD): 64.7 (14.7) 84 NR NR 81 ≥80 Stage IV mBC
Bonechi et al
(2018)64 		Overall study population 31 Median (range): 64 (37–83) 100 93.7 81.2 100 ≥80 mBC
Bonotto et al
(2017)30 		Overall study population 446 Age of women treated with first-line, Median (range) ET: 68 (39–92); and CT:58 (30–81) 100 NR NR 100 ≥80 mBC
Boudin et al (2016)52 Overall study population 235 Median (range):46 (21–62) 62.1 NR NR 82.5 50–79 mBC following treatment with high- dose chemotherapy (HDC) and autologous hematopoietic progenitor cell transplantation (AHSCT)
Carbognin et al. (2016)80 Overall study population 335 Age at diagnosis of metastasis, Median (range): 61 (30–91) 100 92.8 78.8 100 ≥80 advanced BC
Chandarlapaty et al. (2016)68 Overall study population 541 Median (range), Everolimus and exemestane: 62 (34–93); Placebo and exemestane: 61 (28–90) 100 100 NR 100 ≥80 mBC
Chen et al
(2018)41 		Overall sample= 390 analyses conducted in late
recurrence group
(n=109)		 390 Age at diagnosis:
Early recurrence: Age group ≤35: 39 (13.9%); Age group >35: 242 (86.1%). Late recurrence: Age group ≤35: 19 (17.4%); Age group >35: 90 (82.6%)		 100 NR NR 100 ≥80 Patients with BC who relapsed after surgery
Cinausero et al
(2018)37 		Overall study population 410 Age at last line treatment, Median (range):
67.2 (31–92)		 71.0 75.9 60.7 82.2 50–79 mBC
Delpech et al
(2012)57 		Overall study population 241 Median (range): 55 (29–93) NR 100 75 71 50–79 mBC
Demian et al (2011)86 Metastatic subgroup=20 20 NR NR 80 80 65 50–79 mBC
den Brok et al
(2017)91 		Subgroup (HR+/HER2–) Relapse=1,174
De novo: n=406		 Relapsed: Age group ≤50 years: 278 (23.7%)
Age group >50 years: 896 (76.3%) De novo: Age group ≤50 years: 99 (24.4%) Age group
>50 years: 307 (75.6%)		 100 100 NR 100 ≥80 mBC
Desille-
Gbaguidi et al
(2018)94 		Overall study population 139 Mean (SD, range): 62.7 (15.4, 25–94) 80 77.7 65.5 79.9 50–79 mBC
Dominici et al
(2011)89 		Overall study population 290 Mean (SD): Non-surgery: 52.2 (13.6);
Surgery: 53.4 (14.0)		 NR 74.1 NR 67.2 50–79 Stage IV mBC
Elsamany et al
(2014)84 		Overall study population 60 NR 63.3 NR NR 63.3 50–79 mBC
Ercolani et al
(2018)92 		Overall study population 51 Mean (SD, range): 56 (11.4, 37–76) NR 69 47 61 50–79 mBC
Fountzilas et al
(2013)56 		Overall study population 64 Median (range), Group A: 53.4 (32–75) and
Group B: 60.65 (31–74)		 NR 85.4 68.3 88.5 ≥80 mBC
Gampenrieder
et al (2018)42 		Overall study population 116 Median (range), Optimization set: 60 (29–86), Learning set: 61 (34–81) 69 NR NR 100 50–79 mBC
Gamucci et al
(2017)38 		Overall study population 314 Median (range): 55 (27–82) 80.9 NR NR 100 ≥80 mBC
Gerratana et al (2015)63 Overall study population 544 Median (range): 63 (53–73) NR 79.4 63.7 78.9 50–79 mBC
Gilabert et al
(2011)29 		Overall study population 75 Age before starting capecitabine, Median
(range): 53 (36–78)		 79 NR NR 100 50–79 mBC
Giordano et al
(2011)24 		Overall study population 517 Median (range): 49.3 (23.3–82) NR 64.2 43.9 80.5 50–79 mBC
Goetz et al
(2017) (CA)26 		MONARCH 2, overall study population 669 Mean (SD): 59.9 (11.4) 100 NR NR 100 ≥80 mBC
Goetz et al
(2017) (CA)26 		MONARCH 3, overall study population 493 Mean (SD): 63.1 (9.92) 100 NR NR 100 ≥80 mBC
Gong et al
(2018)55 		Overall study population 7,482 NR 74.4 NR NR 67.7 50–79 mBC
Griguolo et al
(2017) (CA)34 		Overall study population 104 Median (range): 56 (26–75) 67.3 NR NR 69.2 50–79 BC patients with leptomeningeal metastasis
Guo et al
(2017)35 		Overall study population 176 Median (range): 49.5 (28–80) NR 56.3 47.7 63.6 50–79 mBC
Inari et al
(2017)45 		Overall study population 96 Mean (SD): 51 (7.5) 60.4 42.7 40.6 85.4 50–79 mBC (metastatic lesions)
Jacot et al
(2018) (CA)47 		Overall study population 72 Median (range): 65 (35–87) NR 69.4 NR 81.9 50–79 mBC
Jansson et al
(2016)74 		Overall study population 52 Age at mBC diagnosis, Median (range): 60 (40–83) 75 88.4 88.4 82.7 50–79 mBC
Jung et al
(2011)43 		Overall study population 553 Median (range): 55 (26–88) 73.1 NR NR 65.5 50–79 mBC
Jung et al
(2012)48 		Overall study population 557 Median (range): 55 (26–88) 73.2 NR NR 65.5 50–79 mBC
Kawano et al
(2013)72 		Overall study population 69 Median (range): 53 (27–86) 100 92 81 87 ≥80 Stage IV, mBC
King et al
(2016)95 		ER-positive/HER2–
negative subgroup		 92 Median (range): 52 (21–79) 100 100 NR 100 ≥80 Stage IV BC
Kobayashi et al
(2016)53 		Overall study population 527 Age starting treatment for mBC, Mean: 55 65.3 NR NR 71.2 50–79 mBC
Kono et al
(2018)87 		Overall study population 389 NR 68.8 NR NR 91 50–79 Untreated primary BC and distant metastasis at diagnosis
Kontani et al
(2014)49 		Overall study population 70 Median (range): 60 (32–81) 60 NR NR 81.8 50–79 mBC
Korantzis et al
(2012)44 		Overall study population 159 Median (range): 60.7 (27.3–86.7) 70 NR NR 62 50–79 mBC
Lau et al (2017) (CA)97 Overall study population 82 NR 100 NR NR 100 ≥80 mBC
Lawrie et al
(2018)96 		Overall study population 103 Median (range): 58 (27–86) 100 100 91 HER2–
(Score 0
+1)
=86.4		 ≥80 mBC
Leone et al
(2017)78 		Overall study population 9,143 Median (range): 61 (19–102) 65.9 NR NR 51.3 50–79 Stage IV BC at initial diagnosis
Li 201738 Overall study population
Overall study population		 7,199 Median: 58 (IQR 49–67) NR 73.4 60.6 74 50–79 Stage IV BC
Llombart-
Cussac et al. (2014)71 		Overall study population 2,203 Median (range): 53 (22–93) 69 65 54 100 50–79 Advanced locally recurrent or mBC
Lobbezoo et al
(2013)10 		Overall study population 798 Median (range): 59 (25–93) 76.5 NR NR 81.4 50–79 mBC
Lobbezoo et al
(2015)69 		Overall study population 815 Median (range), De novo: 61 (25–89); Recurrent: 64 (25–93) 75 NR NR 78 50–79 mBC
Lobbezoo et al
(2016)54,99 		Overall study population 482 Median (range), Initial CT: 52 (25–80), Initial ET: 61 (30–91) 100 NR NR 100 ≥80 mBC
Manuel et al
(2012)59 		Overall study population and subgroups 133 Median (range), Cohort A: 59.9 (36.5–84.1), Cohort B: 56.9 (34.7–79.9) NR 72.1 58.6 73.7 50–79 mBC
Miyoshi,
201638 		Overall study population 318 NR 100 100 100 100 ≥80 Early and late recurrent BC
Motomura
et al (2010)46 		Overall study population 41 Median (range): 57 (42–79) 100 97.6 97.5 92.7 ≥80 mBC
Muller et al
(2012)75 		Overall study population 245 Median: 57 NR 69.4 59.2 56.7 50–79 mBC
Munzone et al
(2012)83 		Overall study population 203 Median (range): 57 (31–78) 79.3 NR NR 73.8 50–79 mBC
Nieder et al
(2017)79 		Overall study population 118 Median (range): 61 (33–87) NR 77 NR 82 50–79 mBC
Ogiya et al
(2017)66,67 		Overall study population 339 NR NR 100 NR 100 ≥80 BC patients with the early and late distant recurrence
Okazaki et al
(2018)67 		Overall study population 18 Median (range): 51 (34–81) 100 NR 83 100 ≥80 Locally advanced or mBC
Paoletti et al
(2017) (CA)31 		Overall study population 121 NR NR 100 NR 100 ≥80 mBC
Papadaki et al
(2018)32 		Overall sample = 130
Analysis conducted in
HER2– subgroup		 130 Median (range): 59 (23–82) NR 68.5 63.8 78.5 50–79 mBC
Park et al
(2017)85 		Overall study population 100 Mean (range): 48.1 (48–75) 65 NR NR 75 50–79 Invasive ductal BC with bone-only metastasis
Pascual et al
(2017)65 		Overall study population 90 Median (range): 62 (37–84) NR 100 NR 100 ≥80 mBC
Peeters et al
(2014)36 		Overall study population 154 Median (range): 62.1 (32.9–90.8) 55.2 NR NR 69.9 50–79 mBC
Pierga et al (2012)51 Overall study population 267 Median: 57 62 NR NR 83 50–79 mBC
Pistilli et al
(2017) (CA)50 		Overall study population 6,265 Median (range),
Age group <45 years: 40.0 (23–44)
Age group >45 years: 63 (45–95)		 100 NR NR 100 ≥80 mBC
Redondo et al
(2018)58 		Overall study population 148 Median (range): 50 (29–81) NR 74.3 61.5 100 50–79 mBC
Ren et al (2016)73 Overall study population 323 Median: 49 NR 58 45 50 50–79 advanced BC
Schiavon et al (2015)23 Subgroup of ESRI wild and mutant type 128 Median, ESR1 wild type: 58, ESR1 mutant: 64 100 100 NR 84 ≥80 advanced BC
Staudigl et al (2015)81 Overall study population 114 Age at first diagnosis, Mean: 61.0 76.3 NR NR 82.5 50–79 mBC
Suh et al (2017)27 Overall study population 66 Age at the time of treatment, Median: 44 100 NR NR 100 ≥80 mBC and recurrent BC (Luminal A, Luminal B (HER2–),Unknown)
Turker et al (2014)98 Overall study population 302 Median (range): 50 (21–83) NR 72.2 60.6 59.6 50–79 Stage IIIC with >10 positive axillary
Uyeturk et al (2014)25 Overall study population 466 Median (range): 50 (18–90) 73.2 68.5 60.5 65.5 50–79 mBC
Vaz-Luis et al (2015)85 HR+ HER2– subgroup 3,151 NR 100 NR NR 100 ≥80 Stage IV, mBC
Wallwiener et al (2013)76 Overall study population 486 Median (range): 55 (23–91) NR 67.3 58.7 69.8 50–79 mBC
Wu et al (2017)90 Overall study population 9,256 NR 76.6 NR NR 74.2 50–79 Stage IV BC
Xie et al
(2015)33 		Overall study population 699 Age at BC diagnosis, Median (range), patients with multiple metastases: 61.0 (35.0–83.0); patients with a single metastasis: 61.0 (33.0–90.0) 100 NR NR 100 ≥80 mBC
Xiong et al
(2018)28 		Overall study population 8,901 NR 70.5 NR NR 65.6 50–79 BC with initial bone metastasis
Yamamura et al
(2018)39 		Overall study population 172 For stage IV:
Age group <50 years: 12 (18%)
Age group 50–70 years: 16 (25%)
Age group ≥70 years: 37 (57%)
For recurrent mBC:
Age group <50 years: 20 (19%)
Age group 50–70 years: 25 (23%)
Age group ≥70 years: 62 (58%)		 100 NR NR 100 ≥80 Stage IV and recurrent and mBC
Yerushalmi
et al (2012)93 		Subgroup Luminal A and
Luminal B		 566 NR 100 NR NR 100 ≥80 mBC
Zhang et al
(2013)60 		Overall study population 134 Median (range): 52 (28–74) 100 NR NR 56 50–79 mBC
Zhao et al
(2011)70 		Overall study population 60 Median (range), Metonomic Arm: 46 (35–73); Conventional Arm: 51 (33–73) NR 66.6 NR 76.6 50–79 Stage IV BC with bone metastases

Abbreviations: BC, breast cancer; CT, chemotherapy; ET, endocrine therapy; IQR, interquartile range; mBC, metastatic breast cancer; NR, not reported; SD, standard deviation.