Table 6.
Univariate and/or mltivariate analysis of survival of breast cancer patients in included studies.
| Refs. | Independent variables in the UA | Independent variables in the MA | Results |
|---|---|---|---|
| Liede A [20] | First site of metastasis, visceral metastases subsequent to BM, | NA | Survival of first site of BM vs synchronous bone and visceral metastases vs visceral metastasis occurred first: |
| 3-yr: 35.1% vs 26.2% vs 18.1%; 5-yr: 12.5% vs 14.1% vs 8.3%. | |||
| The HR for dying with visceral metastases after BM vs BM only: 2.70 (95%CI 1.88–3.87; P < 0.0001) | |||
| Cetin K [21] | NA | Age, ER status, level of comorbidity, presence/absence of other distant metastases at or prior to diagnosis of BM, stage, BMFI | BoS decreased with more advanced stage (IV vs. I-III (adjusted HR = 2.12, 95%CI 1.71–2.62); BoS was highest with a BMFI < 1-yr, however, it increased with longer BMFI for BMFI ≥1-yr. |
| Dibekoglu C [22] | Bone fractures | NA | BoS was not different in patients with or without bone fractures, MBoS: 4-yr vs. 3.25-yr, P = 0.65. |
| Bollen L [23] | Molecular phenotype | NA | Patients with SBM from TNBC have a shorter survival than from RPBC (0.56-yr vs. 1.88-yra, P < 0.001). |
| Foerster R [24] | NA | Age, PSS, ChT prior to RT, number of metastases, local response, concomitant BP, orthopedic corset, PF prior to RT | An age > 50-yr (P < 0.001, HR = 1.036(95%CI 1.015–1.057)), the presence of a single BM (P = 0.002, HR = 0.469, 95%CI 0.292–0.753) and TNBC (P < 0.001, HR = 1.068, 95%CI 0.933–1.125) were identified as independent prognostic factors for BoS. |
| Harries M [25] | Metastases sits | NA | MBoS: bone-only metastases vs. visceral and bone metastases (2.3-yr vs. < 0.91-yr) |
| Steinauer K [26] | Non-systemic locoregional therapy | NA | RT and/or Sur improved MBoS (2.29-yr vs. 1.625-yr, P < 0.001). |
| Chen J [30] | Histological grade, ER status | Age, menopausal status, clinical staging, N, histological grade ER/PR/HER2 status, BMFI | In UA, low-grade and ER positive BC showed significantly prolonged BoS compared with those with high-grade or ER negative ones (χ2 = 0.705, P = 0.019); In MA, ER status (χ2 = 8.315, P = 0.004) and BMFI (χ2 = 6.863, P = 0.009) were independent prognostic factors for BoS, and a histological grade wasn’t one (χ2 = 0.767, P = 0.381). |
| Sung GA [31] | Age, T, N, ER status, histologic grade, BMFI, number of BM, BMA, RT, ChT, HT | ER status, BMFI, number of BM, BAM | In UA, lower N (P = 0.006), BMFI ≥2-yr (P < 0.001), ER positivity (P = 0.027), solitary BM (P < 0.001), HT (P = 0.222), BMA (P < 0.001) showed significantly prolonged BoS; In MA, ER positivity (HR = 0.51, 95%CI 0.28–0.94), solitary BM (HR = 0.32, 95%CI 0.14–0.72), BAM (HR = 0.18, 95%CI 0.07–0.43) were significantly associated with longer BoS. |
| Sathiakumar N [32] | Age, race/ethnicity, stage at cancer diagnosis, PSS, BM, SREs | Age, race/ethnicity, PSS, BM, SREs | In UA, HRs for risk of death were 4.9 (95% CI 4.7–5.1) and 6.2 (95% CI 5.9–6.5), respectively, for women with BM but no SREs and for women with BM plus SREs, compared with women without BM; In MA, HR was 1.5 (95% CI 1.4–1.6) for women with BM plus SREs, compared with women with BM but without SRE. |
| Niikura N [33] | Age, menopausal status, timing of BM diagnosis, DFI, PSS, ER/HER2 status, nuclear grade, number of metastases, bone pain | Treatment, timing of BM diagnosis, PSS, number of metastases, BP | In UA, the time of their primary breast cancer diagnosis, a single metastasis, asymptomatic bone disease, performance status of 0–1 had a longer PFS or/and BoS; In MA, Trastuzumab led to no difference in the BoS among patients with HER2+. |
| Yavas O [38] | Age, menopausal status, T, N, histological type and grade, HR status, LVI, skin involvement, BMFI, additional nonosseous metastatic sites | The same to UA | In UA, T, N, HR status, LVI, skin involvement, additional nonosseous metastatic sites, BMFI had significant prognostic values; In MA, T, HR status, LVI, additional nonosseous metastatic sites were found to have prognostic significance. |
| Cazzaniga ME [39] | The metastatic sites | NA | The 2-yr probability for death was 0.74 (95% CI 0.67–0.79) for BM, 0.38 (95%CI 0.25–0.51) for previous nonskeletal BM and 0.56(95%CI 0.46–0.66) for concomitant nonskeletal BM (P < 0.0001). |
| Briasoulis E [40] | Histological tumor type and grade, M, number of BM | NA | No association noted between MBoS and histological tumor type and grade, M, number of BM. |
| James JJ [41] | Age, ER status, histological grade, additional metastatic sites other than bone, number of hotspots on bone scan, CA153, CEA, radiographic appearance of BM, histological tumor type, N, T, ESR | BMFI, absence of metastases at sites other than bone, ER, CEA CA153 | In UA, ER status (P < 0.0003), histological grade (P < 0.034), additional metastatic sites other than bone (P < 0.0004), age (P < 0.0003), number of hotspots on bone scan (P = 0.040), CA153 (P = 0.0026), CEA (P = 0.017) were found as independent prognostic factors for BoS; In MA, BMFI, additional metastatic sites other than bone, ER status and serological tumor marker levels all independently contributed to BoS. |
| Plunkett TA [42] | The metastatic sites | NA | MBoS: longest in BM only, shortest in BM plus liver metastases (2.1-yr vs.0.46-yr) |
BM, bone metastases; SBM, spinal bone metastases; BMFI, bone metastasis-free interval; SREs, skeletal-related events; BC, breast cancer; RPBC, receptor positive breast cancer; TNBC, triple negative breast cancer; PSS, performance status score; T, tumor size; N, nodal status; M, metastatic status; ER, estrogen receptor; PR, progesterone receptor; HR, hormone receptor; HER2, human epidermal growth factor receptor 2; BMA, bone-modifying agents; RT, radiation therapy; HT, hormonal therapy; ChT, chemotherapy; BoS, bone metastases over survival; MBoS, median bone metastases over survival; PFS, progression-free survival; BP, bisphosphonates; CA153, carbohydrate antigen 153; CEA, carcino embryonie antigen; ESR, erythrocyte sedimentation rate; LVI, lymphovascular invasion; DFI, disease-free interval; vs., versus; HR, hazards ratio; UA, uivariate analysis; MA, mltivariate analysis; NA, not available.
BoS was defined as the time from initial diagnosis of BM until death from any cause; MBoS was defined as the median time from initial diagnosis of BM until death from any cause; PFS was defined as the time interval from diagnosis of BM to progression, death, or the last follow-up date, whichever occurred first.
Survival time was calculated between start of treatment for the spinal metastasis and date of death or last follow-up moment recorded.