Table 3.
Additional Variables Assessed in the Included Studies
| Prognostic Factor | Type of Outcome |
No. of Studies That Assessed Association | No. of Studies Reporting Significant Association | No. of Studies Reporting Worse Outcome | No. of Studies Reporting Better Outcomes | Summary of Direction of Association |
|---|---|---|---|---|---|---|
| Biomarkers or genetic markers | ||||||
| ALDH1 (1 vs >1%) | OS | 1 | 140 | 1 | – | ALDH1 1% was associated with worse OS than ALDH1 >1% |
| ALP (high vs normal) | OS | 2 | 179 | 1 | – | High ALP was associated with worse OS than normal ALP |
| ALP > upper limit of normal | PFS | 1 | 151 | 1 | – | High ALP was associated with worse PFS than normal ALP |
| Baseline SUVmax (intermediate and highest tertile vs lowest tertile) | OS | 1 | 160 | – | – | Baseline SUVmax intermediate and highest tertiles were associated with worse OS than the lowest tertile |
| PFS | 1 | 160 | 1 | – | Baseline SUVmax intermediate and highest tertiles were associated with worse PFS than the lowest tertile | |
| CA 15–3 (high vs normal) | OS | 2 | 179 | 1 | – | Higher levels of CA 15–3 was associated with worse OS compared to normal levels |
| CA 15–3 >upper limit of normal | PFS | 1 | 151 | 1 | – | CA 15–3 > upper limit of normal was associated with worse PFS |
| CEA > upper limit of normal | PFS | 1 | 151 | 1 | – | CEA > upper limit of normal was associated with worse PFS |
| Serum CRP levels (high, >60 vs normal) |
OS | 1 | 179 | 1 | – | Higher serum CRP levels compared to normal was associated with worse OS |
| ESR1 mutations (mutated vs wild type) | OS | 1 | 168 | 1 | – | Mutated ESR1 (D538G, Y537S) was associated with worse OS than wild type |
| PFS | 1 | 168 | 1 | – | Mutated ESR1 (D538G) was associated with worse PFS than wild type | |
| Gamma- glutamyltransferase (GGT) (high vs low risk groups) | OS | 1 | 181 | 1 | – | High risk groups C and D (elevated and highly elevated GGT) was associated with significantly decreased OS time compared to the low risk groups A and B (normal and normal high GGT) |
| GIT1 expression (no vs yes) | OS | 1 | 196 | 1 | – | Loss of GIT1 expression in lymph nodes (± pattern) was associated with worse OS |
| Hemoglobin (<11.5 vs ≥11.5 g/dL) | OS | 2 | 259,79 | 2 | – | Lower hemoglobin levels (<11.5 g/dL) was associated with worse OS compared to high levels (≥11.5 g/dL) |
| HER2 blood mRNA levels (high vs low) | OS | 1 | 144 | – | 1 | High blood HER2 mRNA levels were found to be associated with significantly improved OS compared to low levels |
| IHC, Tau protein (+ vs–) | PFS | 1 | 156 | – | 1 | Presence of Tau protein expression was associated with better PFS |
| IHC, Topo IIa (+ vs–) | PFS | 1 | 156 | 1 | – | Topo IIa protein positivity was associated with unfavorable PFS |
| IL-18 levels (high, ≥8 ng/ mL vs low) | OS | 1 | 186 | – | 1 | High IL-18 levels (≥8 ng/mL) at the time of diagnosis was associated with better OS than low IL-18 levels |
| IL-8 (high vs low) | OS | 1 | 144 | 1 | – | Higher IL-8 levels compared to lower levels was associated with worse OS |
| LBD mutations (yes vs no) | OS | 1 | 197 | 1 | – | Presence of LBD mutations were associated with worse OS |
| PFS | 1 | 197 | 1 | – | Presence of LBD mutations were associated with worse PFS | |
| LDH levels (high, ≥600 vs low <600 UI/mL) | OS | 3 | 351,59,79 | 3 | – | Higher LDH levels was associated with worse OS than lower LDH levels |
| LDH levels (high vs low) | PFS | 1 | 151 | 1 | – | LDH levels > upper limit of normal was associated with worse PFS |
| Lymphocytes (<1 vs ≥1 Giga/L) | OS | 1 | 159 | 1 | – | Lower lymphocyte count was associated with worse OS |
| MAPT RQ values, 50% cut- off (high vs low) | OS | 1 | 156 | – | 1 | High MAPT RQ values was associated with better OS |
| Metastatic EZH2 expression (high vs low) | OS | 1 | 145 | 1 | – | High metastatic EZH2 expression was associated with worse OS than low EZH2 expression |
| NDL (>1 vs ≤1 Giga/L) | OS | 1 | 159 | 1 | – | NDL >1 Giga/L was associated with worse OS than NDL ≤1 Giga/L |
| N-telopeptide of type I collagen (NTx) (<18 nM BCE vs > 18 nM BCE) | PFS | 1 | 170 | – | 1 | Baseline serum NTx of less than 18 nM was associated with significantly better PFS than baseline serum NTx of greater than 18 nM |
| PNN (<7.5 vs ≥7.5 Giga/L) | OS | 1 | 159 | – | 1 | PNN <7.5 Giga/L was associated with better OS than PNN ≥7.5 Giga/L |
| 21-gene recurrence score (low vs high risk group) |
OS | 1 | 195 | – | 1 | Low risk group (<18 score) was associated with better OS than high risk group (≥31 score) |
| Serum albumin (low vs normal) | OS | 1 | 179 | 1 | – | Low serum albumin compared to normal levels was associated with worse OS |
| Serum VEGF after 3 months (normal vs abnormal) | PFS | 1 | 170 | – | 1 | Serum VEGF of less than 500 pg/mL (normal) after 3 months of intervention was associated with better PFS compared to VEGF >500 pg/mL (abnormal) |
| SET(ER/PR) Index (high vs low) | OS | 1 | 197 | – | 1 | Higher SET(ER/PR) Index was associated with better OS |
| SET(ER/PR) Index (high vs low) | PFS | 1 | 197 | – | 1 | Higher SET(ER/PR) Index was associated with better PFS |
| SNP, ABCB1 1236C/T rs1128503 (C vs T or T/C) |
PFS | 1 | 156 | 1 | – | SNP, ABCB1 1236C/T rs1128503 (C) was associated with worse PFS than ABCB1 1236C/T rs1128503 (T or T/C) |
| SNP, ABCB1 2677G/A/T rs2032582 (G or G/A vs T or T/G) | OS | 1 | 156 | 1 | – | SNP, ABCB1 2677G/A/T rs2032582 (G or G/A) was associated with worse OS than ABCB1 2677G/A/T rs2032582 (T or T/G) |
| SNP, ABCB1 3435C/T rs1045642 (C vs T or T/C) |
OS | 1 | 156 | 1 | – | SNP, ABCB1 3435C/T rs1045642 (C) was associated with worse OS than SNP, ABCB1 3435C/T rs1045642 (T or T/C) |
| Surgical margin (negative, R0 vs positive, R1) | OS | 1 | 192 | – | 1 | Negative surgical margin was associated with better OS than positive surgical margin |
| T-cell receptor diversity (≤33 vs >33%) |
OS | 1 | 159 | 1 | – | T-cell receptor diversity of ≤33% compared with >33% was associated with worse OS |
| Demographic or Patient characteristics | ||||||
| BMI (<20 vs 20–24.9) | OS | 1 | 148 | – | 1 | Low BMI was associated with better OS than higher BMI |
| Surgical margin (negative, R0 vs positive, R1) | OS | 1 | 192 | – | 1 | Negative surgical margin was associated with better OS than positive surgical margin |
| T-cell receptor diversity (≤33 vs >33%) |
OS | 1 | 159 | 1 | – | T-cell receptor diversity of ≤33% compared with >33% was associated with worse OS |
| Demographic or Patient characteristics | ||||||
| BMI (<20 vs 20–24.9) | OS | 1 | 148 | – | 1 | Low BMI was associated with better OS than higher BMI |
| Education level (high vs low) | OS | 2 | 243,55 | 1 | 1 | Mixed result (worse and better OS) |
| BCSS | 1 | 155 | 1 | – | Higher education level was associated with worse BCSS | |
| Household income (per $10,000 annual increase) |
OS | 1 | 155 | – | 1 | Higher median household income was associated with better OS |
| BCSS | 1 | 155 | – | 1 | Higher median household income was associated with better BCSS | |
| Insurance status (uninsured vs insured) |
OS | 1 | 155 | 1 | – | Patients who were uninsured had worse OS than those who were insured |
| BCSS | 1 | 155 | 1 | – | Patients who were uninsured had worse BCSS than those who were insured | |
| Marital status (unmarried vs married) | OS | 5 | 528,55,78,85,90 | 5 | –- | Unmarried status was associated with worse OS than married |
| BCSS | 2 | 255,90 | 2 | – | Unmarried status was associated with worse BCSS than married | |
| Menopausal status (yes vs no; post vs pre) | OS | 4 | 259,98 | 2 | – | Presence of menopause was associated with worse OS than absence of menopause; Similarly, postmenopausal status was associated with worse OS compared to postmenopausal status |
| PFS | 3 | 184 | 1 | – | Postmenopausal status was associated with worse PFS compared to postmenopausal status | |
| Received blood transfusion before RT (yes vs no) | OS | 1 | 179 | – | 1 | Receiving blood transfusion before RT was associated with better OS as compared to not receiving |
| Residence type (rural vs urban) | OS | 1 | 155 | 1 | – | Patients from rural residence was associated with worse OS than urban residence |
| BCSS | 1 | 155 | 1 | – | Patients from rural residence was associated with worse BCSS than urban residence | |
| Comorbidities | ||||||
| History of hypertension (yes vs no) |
OS | 2 | 243,48 | 2 | – | History of hypertension was associated with worse OS |
| Jaundice (yes vs no) | OS | 1 | 137 | 1 | – | Presence of jaundice was associated with worse OS |
| Liver function impairment (yes vs no) |
OS | 1 | 137 | 1 | – | Impaired liver function was associated with worse OS |
| Charlson/Deyo score (1 vs 0, ≥2 vs 0) |
OS | 4 | 433,38,48,85 | 4 | – | Higher Charlson/Deyo scores compared to lower scores were associated with worse OS |
| Anorexia/weight loss/ cachexia (yes vs no) |
OS | 1 | 137 | 1 | -– | Presence of anorexia/weight loss/cachexia was associated with worse OS |
| Risk factors (≥2 vs 0/1) | OS | 1 | 171 | 1 | – | Presence of multiple risk factors was associated with worse OS than having a single, or no risk factor |
| Chronic Pulmonary disease (yes vs no) | OS | 2 | 148 | 1 | – | Presence of chronic pulmonary disease was associated with worse OS compared to absence of the condition |
| Miscellaneous | ||||||
| CNS-M (Isolated CNS progression vs CNS-M plus systemic progression) | OS | 1 | 161 | 1 | – | Having isolated CNS compared with CNS-M plus systemic progression was associated with reduced risk of OS |
| Density (high vs low) | PFS | 1 | 184 | 1 | – | High density compared to low was associated with worse PFS |
| Detection of PD-L1 (+)-CTCs (yes vs no) | PFS | 1 | 147 | 1 | – | Detection of PD-L1(+)-CTCs was associated with worse PFS |
| Follow-up interval after diagnosis (2–5 years vs 1 year) | OS | 1 | 188 | 1 | – | Longer follow-up interval after diagnosis compared to shorter was associated with worse OS |
| Laterality (unknown vs right) | OS | 1 | 128 | – | 1 | Unknown laterality was associated with better OS than right laterality |
| Lymph node ratio (>0.75 vs 0.75) | OS | 1 | 198 | 1 | – | Higher lymph node ratio was associated with worse OS |
| Neutrophil-lymphocyte ratio (NLR) | OS | 1 | 162 | 1 | – | A higher NLR at diagnosis was associated with worse OS than lower NLR |
| Prescribing physician (BC specialist vs others) |
OS | 1 | 137 | – | 1 | Evaluation of a BC specialist compared with others was associated with lower risk of death within 30 days |
| Response status based on PET (responder vs non- responder) | OS | 1 | 182 | –- | 1 | Responders were associated with better OS than non-responders based on PET imaging |
| SEER region (Detroit, Kentucky vs California) | OS | 1 | 185 | 1 | – | Patients from SEER regions including Detroit and Kentucky were associated with worse OS as compared to patients from California |
Abbreviations: ALDH1, aldehyde dehydrogenase 1; ALP, alkaline phosphatase; BC, breast cancer; BCE, bone collagen equivalents per liter; BMI, body mass index; CA 15–3, cancer antigen 15–3; CEA, carcinoembryonic antigen; CRP, C-reactive protein; ESR1, estrogen receptor 1; EZH2, enhancer of zeste homolog 2; GIT1, G-protein-coupled receptor kinase interacting protein 1; IHC, immunohistochemistry; IL-18, interleukin-18; LBD, ligand-binding domain; LDH, lactate dehydrogenase; MAPT RQ, microtubule-associated protein tau; NDL, numeration and diversity of lymphocytes or lympho-divpenic status; NLR, neutrophil-lymphocyte ratio; PET, positron emission tomography; PNN, poly nuclear neutrophils; SET(ER/PR), cumulative measure of gene expression for transcripts associated with estrogen and progesterone receptors; SNP, single nucleotide polymorphism; SUVmax, maximum standard unit value; VEGF, vascular endothelial growth factor.