Limits...
FKBPL: a marker of good prognosis in breast cancer.

Nelson L, McKeen HD, Marshall A, Mulrane L, Starczynski J, Storr SJ, Lanigan F, Byrne C, Arthur K, Hegarty S, Ali AA, Furlong F, McCarthy HO, Ellis IO, Green AR, Rakha E, Young L, Kunkler I, Thomas J, Jack W, Cameron D, Jirström K, Yakkundi A, McClements L, Martin SG, Gallagher WM, Dunn J, Bartlett J, O'Connor D, Robson T - Oncotarget (2015)

Bottom Line: The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004).For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively).A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively).

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.

ABSTRACT
FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14-1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.

No MeSH data available.


Related in: MedlinePlus

Hazard ratio plot of breast cancer specific survival against FKBPL levels by cohort using a one stage random effects meta-analysis model (n = 3279)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4494933&req=5

Figure 3: Hazard ratio plot of breast cancer specific survival against FKBPL levels by cohort using a one stage random effects meta-analysis model (n = 3279)

Mentions: With a median follow-up of 12 years (interquartile range 10–15 years), there were a total of 913 (28%) breast cancer deaths and 1295 (40%) recurrences within the combined cohort of 3277 patients. Within the individual cohorts, breast cancer specific survival (BCSS; Figure 2) was significantly different across FKBPL expression groups within cohorts I (p = 0.004, Figure 2A), II (p = 0.04, Figure 2B) and III (p = 0.001, Figure 2C), but not within cohorts IV (p = 0.93, Figure 2D) and V (p = 0.36, Figure 2E) with lower FKBPL levels associated with poor BCSS (e.g. within cohort I: Hazard ratio (HR) = 1.71 (95% Confidence Interval (CI) 1.19–2.47, Figure 3). The meta-analysis of these five cohorts (n = 3277) was performed using a one stage random effects model, as there appeared to be some heterogeneity between the cohorts (χ2 = 8.8, p = 0.07, Figure 3). Patients with lower FKBPL levels had significantly shorter BCSS than those with higher FKBPL levels (HR = 1.31, 95% CI 1.15–1.50, p < 0.001, Figure 3). In a multivariate random effects analysis, the effect of FKBPL on BCSS remained significant after adjusting for other known prognostic factors, including; tumor size, grade, nodal status, ER and PR status with time dependent covariates (HR = 1.25, 95% CI 1.07–1.45, p = 0.004), and after the addition of Her2 status as a time dependent covariate (HR = 1.21, 95% CI 1.06–1.42, p = 0.02). FKBPL was also significant after adjusting for the Nottingham Prognostic Index (NPI) (HR = 1.31, 95% CI 1.14–1.50, p = 0.0002); which was available in cohorts I, II, III, V (>3000 patients).


FKBPL: a marker of good prognosis in breast cancer.

Nelson L, McKeen HD, Marshall A, Mulrane L, Starczynski J, Storr SJ, Lanigan F, Byrne C, Arthur K, Hegarty S, Ali AA, Furlong F, McCarthy HO, Ellis IO, Green AR, Rakha E, Young L, Kunkler I, Thomas J, Jack W, Cameron D, Jirström K, Yakkundi A, McClements L, Martin SG, Gallagher WM, Dunn J, Bartlett J, O'Connor D, Robson T - Oncotarget (2015)

Hazard ratio plot of breast cancer specific survival against FKBPL levels by cohort using a one stage random effects meta-analysis model (n = 3279)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494933&req=5

Figure 3: Hazard ratio plot of breast cancer specific survival against FKBPL levels by cohort using a one stage random effects meta-analysis model (n = 3279)
Mentions: With a median follow-up of 12 years (interquartile range 10–15 years), there were a total of 913 (28%) breast cancer deaths and 1295 (40%) recurrences within the combined cohort of 3277 patients. Within the individual cohorts, breast cancer specific survival (BCSS; Figure 2) was significantly different across FKBPL expression groups within cohorts I (p = 0.004, Figure 2A), II (p = 0.04, Figure 2B) and III (p = 0.001, Figure 2C), but not within cohorts IV (p = 0.93, Figure 2D) and V (p = 0.36, Figure 2E) with lower FKBPL levels associated with poor BCSS (e.g. within cohort I: Hazard ratio (HR) = 1.71 (95% Confidence Interval (CI) 1.19–2.47, Figure 3). The meta-analysis of these five cohorts (n = 3277) was performed using a one stage random effects model, as there appeared to be some heterogeneity between the cohorts (χ2 = 8.8, p = 0.07, Figure 3). Patients with lower FKBPL levels had significantly shorter BCSS than those with higher FKBPL levels (HR = 1.31, 95% CI 1.15–1.50, p < 0.001, Figure 3). In a multivariate random effects analysis, the effect of FKBPL on BCSS remained significant after adjusting for other known prognostic factors, including; tumor size, grade, nodal status, ER and PR status with time dependent covariates (HR = 1.25, 95% CI 1.07–1.45, p = 0.004), and after the addition of Her2 status as a time dependent covariate (HR = 1.21, 95% CI 1.06–1.42, p = 0.02). FKBPL was also significant after adjusting for the Nottingham Prognostic Index (NPI) (HR = 1.31, 95% CI 1.14–1.50, p = 0.0002); which was available in cohorts I, II, III, V (>3000 patients).

Bottom Line: The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004).For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively).A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively).

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Queen's University Belfast, Belfast, United Kingdom.

ABSTRACT
FK506-binding protein-like (FKBPL) has established roles as an anti-tumor protein, with a therapeutic peptide based on this protein, ALM201, shortly entering phase I/II clinical trials. Here, we evaluated FKBPL's prognostic ability in primary breast cancer tissue, represented on tissue microarrays (TMA) from 3277 women recruited into five independent retrospective studies, using immunohistochemistry (IHC). In a meta-analysis, FKBPL levels were a significant predictor of BCSS; low FKBPL levels indicated poorer breast cancer specific survival (BCSS) (hazard ratio (HR) = 1.30, 95% confidence interval (CI) 1.14-1.49, p < 0.001). The prognostic impact of FKBPL remained significant after adjusting for other known prognostic factors (HR = 1.25, 95% CI 1.07-1.45, p = 0.004). For the sub-groups of 2365 estrogen receptor (ER) positive patients and 1649 tamoxifen treated patients, FKBPL was significantly associated with BCSS (HR = 1.34, 95% CI 1.13-1.58, p < 0.001, and HR = 1.25, 95% CI 1.04-1.49, p = 0.02, respectively). A univariate analysis revealed that FKBPL was also a significant predictor of relapse free interval (RFI) within the ER positive patient group, but it was only borderline significant within the smaller tamoxifen treated patient group (HR = 1.32 95% CI 1.05-1.65, p = 0.02 and HR = 1.23 95% CI 0.99-1.54, p = 0.06, respectively). The data suggests a role for FKBPL as a prognostic factor for BCSS, with the potential to be routinely evaluated within the clinic.

No MeSH data available.


Related in: MedlinePlus