Systematic review and meta-analysis of C-reactive protein as a biomarker in breast cancer

Mikkelsen, Marta Kramer; Lindblom, Nana Aviaja Frederikke; Dyhl-Polk, Anne; Juhl, Carsten Bogh; Johansen, Julia S.; Nielsen, Dorte L.

doi:10.1080/10408363.2022.2050886

Cited by 16 publications

(8 citation statements)

References 70 publications

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“…Prior literature has shown inconsistent results regarding the prognostic value of CRP in BC. The metaanalysis by Mikkelsen et al suggested a limited potential for CRP as a prognostic marker in nonmetastatic settings [19]. In studies using CRP as a categorical variable, high CRP was associated with lower DFS and OS, but the estimates were imprecise.…”

Section: Discussionmentioning

confidence: 99%

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Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups

Holm,

Baggesen,

Cronin-Fenton

et al. 2024

Preprint

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Purpose Obesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI). Methods We assembled a cohort of women with BC (stage I-III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2,673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up. We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95%CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). Results During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years). For DFS, high CRP (CRP ≥ 3.24 mg/L) was associated with an increased risk of events (HRadj:1.58 [95%CI = 1.12–2.24]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95%CI = 1.09–2.66]; HRadj:1.75 [95%CI = 1.08–2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95%CI = 0.78–3.83]). For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95%CI = 1.62–3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95%CI = 1.95–6.87]; HRadj:1.92 [95%CI = 1.06–3.46]), but less clear in obesity (HRadj:1.40 [95%CI = 0.64–3.09]). Conclusion High CRP levels at BC diagnosis were associated with inferior prognosis in early BC irrespective of BMI, although less clear in patients with obesity.

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Section: Discussionmentioning

confidence: 99%

“…Likewise, in a meta-analysis from 2011, Han et al reported an association between elevated CRP levels and lower OS and DFS [18]. A meta-analysis by Mikkelsen et al found that high CRP was an indicator of poor prognosis in metastatic BC, but the prognostic value in non-metastatic early BC could not be con rmed [19].…”

Section: Introductionmentioning

confidence: 99%

Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups

Holm,

Baggesen,

Cronin-Fenton

et al. 2024

Preprint

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“…Recently, many meta-analyses have explored whether CRP can be used to predict the prognosis of different solid tumors [ 45 – 47 ]. According to a meta-analysis including 16 studies by Zhou et al [ 45 ], higher CRP levels were associated with worse OS, cancer-specific survival, and PFS in prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Prognostic and clinicopathological significance of C-reactive protein in patients with ovarian cancer: a meta-analysis

Zhang,

Qian

2024

World J Surg Onc

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Background Many studies have explored the relationship between C-reactive protein (CRP) levels and survival outcomes in patients with ovarian cancer (OC); however, consistent results have not been reported. As such, this meta-analysis was performed to accurately assess the prognostic and clinicopathological roles of CRP in OC. Methods The PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for relevant studies published from inception to April 7, 2023. The effect of CRP level(s) and OC prognostic outcomes was analyzed by computing the combined hazard ratio (HR) and corresponding 95% confidence interval (CI). Thereafter, the association between CRP level(s) and clinicopathological factors was evaluated using a combined odds ratio (OR) and corresponding 95% CI. Results The present meta-analysis included 15 studies comprising 3202 subjects. According to the combined data, higher CRP levels were markedly associated with unfavorable overall survival (OS) (HR 1.23 [95% CI 1.11–1.37]; p < 0.001) and progression-free survival (PFS) (HR 1.55 [95% CI 1.30–1.84]; p < 0.001) in patients with OC. Furthermore, the results indicated that high CRP levels were significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stages III–IV (p < 0.001), residual tumor size ≥ 1 cm (p < 0.001), histological grade 3 (p = 0.040), and ascites volume ≥ 500 mL (p < 0.001). Conclusion The results of this meta-analysis demonstrated that higher serum CRP levels were strongly associated with dismal OS and PFS in subjects with OC. High CRP levels were also significantly associated with clinical factors implicated in tumor aggressiveness and the development of OC.

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“…Compared to AFP, CRP’s prognostic value in HCC has been reported in the literature but has not been extensively studied [ 16 – 18 , 36 ]. CRP is an effective biomarker and is associated with the progression of several malignancies [ 37 – 40 ]. Elevated CRP is associated with decreased survival rates in both resectable and non-resectable HCC patients [ 41 – 43 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients

Lin,

Chen,

Tang

et al. 2023

BMC Cancer

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Background Routine clinical staging for hepatocellular carcinoma (HCC) incorporates liver function, general health, and tumor morphology. Further refinement of prognostic assessments and treatment decisions may benefit from the inclusion of tumor biological marker alpha-fetoprotein (AFP) and systemic inflammation indicator C-reactive protein (CRP). Methods Data from a multicenter cohort of 2770 HCC patients undergoing hepatectomy were analyzed. We developed the PACE risk score (Prognostic implications of AFP and CRP Elevation) after initially assessing preoperative AFP and CRP’s prognostic value. Subgroup analyzes were performed in BCLC cohorts A and B using multivariable Cox analysis to evaluate the prognostic stratification ability of the PACE risk score and its complementary utility for BCLC staging. Results Preoperative AFP ≥ 400ng/mL and CRP ≥ 10 mg/L emerged as independent predictors of poorer prognosis in HCC patients who underwent hepatectomy, leading to the creation of the PACE risk score. PACE risk score stratified patients into low, intermediate, and high-risk groups with cumulative 5-year overall (OS) and recurrence-free survival (RFS) rates of 59.6%/44.9%, 43.9%/38.4%, and 20.6%/18.0% respectively (all P < 0.001). Increased PACE risk scores correlated significantly with early recurrence and extrahepatic metastases frequency (all P < 0.001). The multivariable analysis identified intermediate and high-risk PACE scores as independently correlating with poor postoperative OS and RFS. Furthermore, the PACE risk score proficiently stratified the prognosis of BCLC stages A and B patients, with multivariable analyses demonstrating it as an independent prognostic determinant for both stages. Conclusion The PACE risk score serves as an effective tool for postoperative risk stratification, potentially supplementing the BCLC staging system.

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Systematic review and meta-analysis of C-reactive protein as a biomarker in breast cancer

Cited by 16 publications

References 70 publications

Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups

Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups

Prognostic and clinicopathological significance of C-reactive protein in patients with ovarian cancer: a meta-analysis

Prognostic implications of alpha-fetoprotein and C-reactive protein elevation in hepatocellular carcinoma following resection (PACE): a large cohort study of 2770 patients

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