Table 3 Predictors of Survival Among Patients with HER2+ Breast Cancer and Brain Metastasis
Citation | Predictors for Shorter Time to Death (i.e., Survival) After BM Diagnosis | ||||||||
|---|---|---|---|---|---|---|---|---|---|
HER2+ Group | Sample Size, n | Median Time to Death After BM Diagnosis, mo | Age | HR Status | No. of Brain Lesions | Anti-HER2 Therapy | Any Systemic Treatment | Other | |
Ahn et al., 2013 [17] | Without trastuzumab | 39 | 19.1a | NR | NR | NR | No trastuzumab vs. trastuzumab | NR | NR |
With trastuzumab | 47 | 26.9a | |||||||
Anders et al., 2011 [15] | HR- | 18 | 14.3 (95% CI, 3.2–36.2) | No association | No association | NR | NR | NR | Race (no association) |
HR+ | 21 | 15.2 (95% CI, 7.8–40.4) | |||||||
Anwar et al., 2021 [32] | All | 39 | 13.93 (95% CI 10.53–20.67)b | NR | No association | NR | NR | NR | ▪ Number of prior lines of therapy (no association) ▪ Liver metastasis (no association) ▪ Lung metastasis (no association) ▪ Bone metastasis (no association) |
Bergen et al., 2021 [19] | All | 252 | Before 2000: 12 2000–2010: 11 After 2010: 22 | Included in DS-GPA but not reported independently | Included in DS-GPA but not reported independently | NR | ▪ No HER2-targeted therapy vs. therapy with trastuzumab + pertuzumab, or trastuzumab alone, or lapatinib alone, or T-DM1 alone ▪ Other HER2-targeted therapy vs. trastuzumab + pertuzumab ▪ No HER2-targeted therapy vs. trastuzumab + lapatinib (no association) | NR | ▪ DS-GPA ▪ Time period (year) of initial BC diagnosis (< 2000, 2000–2010, > 2010) (no association) |
Berghoff et al., 2012 [30] | All | 102 | 7 (95% CI, 4.3–969) | NR | NR | NR | ▪ Local therapyc alone vs. trastuzumab-based therapy after local therapy | NR | NR |
Braccini et al., 2013 [36] | All | 109 | 11.9 (95% CI, 8.7–15.5) | NR | No association | NR | ▪ No anti-HER2 therapy vs. anti-HER2 therapy ▪ Trastuzumab alone or lapatinib alone vs. trastuzumab + lapatinib (sequentially) | NR | NR |
Brufsky et al., 2011 [31] | All | 377 | 13.0 (range, 0.1–55.5)d | No association | No association | NR | ▪ No trastuzumab vs. trastuzumab | ▪ No chemotherapy vs. chemotherapy | ▪ No surgery vs. surgery ▪ Radiotherapy – no association ▪ ECOG PS ≥ 2 vs. 0 or 1 ▪ CNS disease at mBC diagnosis vs. no CNS disease at mBC diagnosis |
Duchnowska et al., 2012 [21] | All | 142 | 28 (95% CI, 16–32) | NR | NR | NR | ▪ NR | NR | NR |
Gori et al., 2019 [24] | All | 154 | 24.5 | ≥ 60 y vs. < 60 y at BM diagnosise | No association | > 3 vs. 1–3 BMse | ▪ Systemic therapy without HER2-targeted agents or no systemic therapy vs. HER2-targeted agents | NR | ▪ WBRT or no local treatment vs. surgery and/or SRS ▪ KPS ≤ 7 0 vs. > 70 ▪ Presence of neurologic symptoms |
Hayashi et al., 2015 [25] | ER+ | 162 | 16.5 (95% CI, 11.9–21.1) | NR | No association | > 3 vs. ≤ 3 BMs | ▪ Neither trastuzumab nor lapatinib vs. at least one of these after BM diagnosis ▪ Either trastuzumab alone, lapatinib alone, or no HER2-targeting agent vs. trastuzumab and lapatinib after BM diagnosis | NR | NR |
ER- | 270 | 11.5 (95% CI, 9.1–13.8) | |||||||
Heitz et al., 2009 f [29] | All | 245 | 11 | NR | NR | NR | ▪ NR | NR | ▪ NR |
Jang et al., 2011 [34] | All | 137 | 5.2 (95% CI, 3.6–6.8) | NR | NR | NR | ▪ NR | NR | ▪ NR |
Kaplan et al., 2012 [33] | ER−/PR- | 102 | 11.04 (95% CI, 6.18–15.90) | ≥ 46 y vs. < 46 y at BM diagnosise (suggestive association in multivariable analyses) | No association | > 3 vs. ≤ 3 BMse (suggestive association in multivariable analyses) | ▪ Trastuzumab- or lapatinib-based therapy alone vs. trastuzumab- and lapatinib-based therapy (sequential) ▪ Trastuzumab-based therapy alone vs. lapatinib-based therapy alone | NR | ▪ KPS ≤ 70 vs. > 70 ▪ Tumor grade 3 vs. grade 1–2 ▪ ≥ 2 vs. < 2 metastatic sites outside the brain ▪ No neurosurgery vs. neurosurgery ▪ No radiosurgery vs. radiosurgery |
Luminal Bf | 113 | 9.99 (95% CI, 4.99–14.98) | |||||||
Kuba et al., 2014 [35] | All | 26 | 23 (95% CI, 14–31) | No association | NR | No association | ▪ NR | NR | ▪ PS ≥ 2 vs. 0/1 ▪ Undergoing surgery or SRS (no association) |
Martin et al., 2017 [38] | HR+ | 136 | 21 (IQR: 6-not reached)g | NR | NR | NR | ▪ NR | NR | ▪ NR |
HR- | 106 | 10 (IQR: 4–27)g | |||||||
Maurer et al., 2018 [26] | All | 483 | 20.8 (IQR: 5.36-not reached) | NR | NR | NR | ▪ No association | NR | ▪ CNS symptomsh vs. no CNS symptoms at BM diagnosis |
Morikawa et al., 2018 [27] | All | 100 | 19.4 (95% CI, 15.5–26.6) | No association | No association | Multiple lesions vs. single lesion | ▪ No anti-HER2 use vs. anti-HER2 use after BM diagnosis ▪ No anti-HER2 use vs. lapatinib use after BM diagnosis | NR | ▪ KPS < 70 vs. ≥ 70 ▪ Neurologic symptoms vs. no neurologic symptoms ▪ Uncontrolled extracranial disease vs. controlled |
Mounsey et al., 2018 [20] | All | 123 | 18.1 (95% CI, 14.9–24.6) | NR | NR | NR | ▪ No HER2-targeted therapy vs. HER2-targeted therapy after BM diagnosis | NR | ▪ NR |
Niwinska et al., 2010 [39] | All | 109 | 9 (range, 0.6–3.4) | NR | NR | NR | ▪ No systemic therapy or chemotherapy without trastuzumab vs. chemotherapy with trastuzumab | WBRT alone vs. systemic therapyi after WBRT | ▪ KPS < 70 vs. ≥ 70 ▪ RPA RTOG Prognostic class III vs. class I/II ▪ Visceral metastasis vs. no visceral metastasis |
Sperduto et al., 2013 [37] | HR+ | 98 | 22.9 (95% CI, 16.1–29.5) | NR | NR | NR | ▪ NR | NR | ▪ NR |
HR- | 119 | 17.9 (95% CI, 13.4–22.9) | |||||||
Witzel et al., 2018 [16] | All | 732 | 11.6 (95% CI, 10.0–13.4) | NR | NR | NR | ▪ NR | NR | ▪ NR |
Yap et al., 2012 [18] | All | 280 | 10.9 (95% CI, 9.0–11.9) | Older age vs. younger age at BM | NR | Multiple lesions vs. single lesion | ▪ No anti-HER2 treatment vs. anti-HER2 treatment after BM diagnosis ▪ No anti-HER2 treatment or trastuzumab alone vs. lapatinib alone after BM diagnosis ▪ No anti-HER2 treatment vs. trastuzumab alone after BM diagnosis ▪ Anti-HER2 therapy before BM (no association with survival after BM) | ▪ No chemotherapy vs. receipt of chemotherapy after BM diagnosis ▪ No hormonal therapy vs. receipt of hormonal therapy after BM | ▪ NR |
Zhang et al., 2016 [28] | All | 60 | 12 (range, 1–94) | < 50 y vs. ≥ 50 y at BM diagnosise | No association | Multiple lesions vs. single lesione | ▪ No anti-HER2 therapy after WBRT vs. anti-HER2 therapy after WBRT ▪ No systemic therapy, anti-HER2 therapy alone, or chemotherapy alone after WBRT vs. both anti-HER2 therapy and chemotherapy after WBRT | [See “Anti-HER2 therapy” column] | ▪ Uncontrolled extracranial metastasis vs. controlled ▪ KPS < 70 vs. ≥ 70e ▪ Total dose radiotherapy (no association)e ▪ Time from BC diagnosis to BM diagnosis (no association)e |