Biochemical Markers for Monitoring Response to Therapy: Evidence for Higher Bone Specificity by a Novel Marker Compared with Routine Markers

Leeming, Diana Julie; Hegele, Axel; Byrjalsen, I.; Hofmann, Rainer; Qvist, Per; Karsdal, Morten A.; Schrader, Andres Jan; Wagner, Reinhold; Olbert, P.

doi:10.1158/1055-9965.epi-07-2697

Cited by 16 publications

(14 citation statements)

References 29 publications

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“…Mammographic density may therefore include effects of an altered matrix composition, in turn associated with carcinogenesis, whereas the tissue organization (MTR) may provide a score associated with local disorganization. The biological understanding of this being independent from matrix composition (density), may find support in other connective tissues and pathologies [29]. As tissue density and tissue distribution (MTR) were uncorrelated risk factors, this further supports that both accumulation and distribution are equally important for tissue function.…”

Section: Discussionmentioning

confidence: 79%

Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

et al. 2014

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IntroductionBreast density has been established as a major risk factor for breast cancer. We have previously demonstrated that mammographic texture resemblance (MTR), recognizing the local texture patterns of the mammogram, is also a risk factor for breast cancer, independent of percent breast density. We examine if these findings generalize to another population.MethodsTexture patterns were recorded in digitalized pre-diagnosis (3.7 years) film mammograms of a nested case–control study within the Dutch screening program (S1) comprising of 245 breast cancers and 250 matched controls. The patterns were recognized in the same study using cross-validation to form resemblance scores associated with breast cancer. Texture patterns from S1 were examined in an independent nested case–control study within the Mayo Mammography Health Study cohort (S2) of 226 cases and 442 matched controls: mammograms on average 8.5 years prior to diagnosis, risk factor information and percent mammographic density (PD) estimated using Cumulus were available. MTR scores estimated from S1, S2 and S1 + S2 (the latter two as cross-validations) were evaluated in S2. MTR scores were analyzed as both quartiles and continuously for association with breast cancer using odds ratios (OR) and adjusting for known risk factors including age, body mass index (BMI), and hormone usage.ResultsThe mean ages of S1 and S2 were 58.0 ± 5.7 years and 55.2 ± 10.5 years, respectively. The MTR scores on S1 showed significant capability to discriminate cancers from controls (area under the operator characteristics curve (AUC) = 0.63 ± 0.02, P <0.001), which persisted after adjustment for PD. S2 showed an AUC of 0.63, 0.61, and 0.60 based on PD, MTR scores trained on S2, and MTR scores trained on S1, respectively. When adjusted for PD, MTR scores of S2 trained on S1 showed an association with breast cancer for the highest quartile alone: OR in quartiles of controls as reference; 1.04 (0.59 to 1.81); 0.95 (0.52 to 1.74); 1.84 (1.10 to 3.07) respectively. The combined continuous model with both PD and MTR scores based on S1 had an AUC of 0.66 ± 0.03.ConclusionsThe local texture patterns associated with breast cancer risk in S1 were also an independent risk factor in S2. Additional textures identified in S2 did not significantly improve risk segregation. Hence, the textural patterns that indicated elevated risk persisted under differences in X-ray technology, population demographics, follow-up time and geography.

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Section: Discussionmentioning

confidence: 79%

Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

et al. 2014

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“…In this study, B-ALP (but not S-CTX and total ALP) responded to chemotherapy (24% decrease over 30 days). In a group of hormone refractory prostate cancer patients (n 5 40), S-CTX and total ALP did not decrease with Docetaxel therapy in patients without BM (13). However, it decreased with Docetaxel/Zoledronate treatment in those with BM (13).…”

Section: Resultsmentioning

confidence: 97%

Lectin affinity electrophoresis of serum alkaline phosphatase in metastasized breast cancer

Bricon¹,

Gay-Bellile²,

Cottu³

et al. 2010

Clinical Laboratory Analysis

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The use of serum alkaline phosphatase (ALP) isoenzymes as markers of breast cancer metastases and treatment efficacy has received little attention. Twenty-six breast cancer women (56+/-13 years, all post-menopausal) were prospectively evaluated during their first and third course of chemotherapy (4-week interval). Serum samples were analyzed for ALP isoenzymes (bone, liver, and intestine) using a lectin affinity electrophoresis kit (Hydragel 15 ISO-PAL, Sebia) adapted on a semi-automated Hydrasys system (Sebia). Results were compared with imaging techniques for the presence of metastases; bone ALP isoenzyme (B-ALP) results were compared with C-Terminal degradation products of type I collagen (S-CTX) (CrossLaps, IDS Nordic). Serum B-ALP, but not S-CTX, confirmed the presence of bone metastases (BM) (n=15) with 67/100% sensitivity/specificity (using a 69 UI/L ROC cut-off); ROC AUC was 0.806 (P=0.0004) (NS for S-CTX). Chemotherapy reduced serum B-ALP by 24% over 4 weeks (P=0.0012); there was no change for S-CTX. There was no specific clinical pattern for other ALP isoenzymes (liver and intestine). In conclusion, serum B-ALP, but not S-CTX, could help confirm the presence of BM in breast cancer patients.

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“…It has been demonstrated that bisphosphonates, especially those of the last generation, induce a decrease in bone turnover marker expression, resulting in a significant reduction in skeletal complications and cancer-related deaths [4,5]. On the basis of this clinical evidence and of results from preclinical studies on the antitumor activity of different molecules, including zoledronic acid, bisphosphonates have been introduced into clinical practice as adjuvant treatment for the prevention of BM [6,7].…”

Section: Introductionmentioning

confidence: 99%

The Role of CXCR4 in the Prediction of Bone Metastases from Breast Cancer: A Pilot Study

et al. 2011

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Objective: The chemokine receptor CXCR4 is involved in tumor growth and homing of cancer cells to distant sites. The aim of our retrospective case-control study was to evaluate whether CXCR4 expression is more effective than conventional markers (estrogen receptor and HER-2) in predicting bone relapse in breast cancer. Methods: CXCR4 expression was evaluated by immunohistochemical staining in paraffin-embedded tissue sections of primary breast cancers from 20 patients with bone metastases (BM), 10 with visceral metastases (VM) and 10 with no evidence of disease (NED) at a median follow-up of 10.5 years (range 10.1–11.8). Results: Cytoplasmic CXCR4 expression was high in BM patients (45%, 95% CI 23–67), much lower in NED patients (10%, 95% CI 0–29) and negative in the VM group. CXCR4 coexpression in the nucleus and cytoplasm was observed in about half of the BM patients (45%) but never in NED or VM patients (p = 0.013). Conversely, estrogen receptor-positive and HER-2-negative status identified 80 and 95% of bone relapse patients, respectively, but did not discriminate between cases and controls. Conclusions: Our results suggest a pivotal role of CXCR4 expression as a predictor of BM in primary breast cancer. A larger study is ongoing to confirm these results.

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Biochemical Markers for Monitoring Response to Therapy: Evidence for Higher Bone Specificity by a Novel Marker Compared with Routine Markers

Cited by 16 publications

References 29 publications

Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

Mammographic texture resemblance generalizes as an independent risk factor for breast cancer

Lectin affinity electrophoresis of serum alkaline phosphatase in metastasized breast cancer

The Role of CXCR4 in the Prediction of Bone Metastases from Breast Cancer: A Pilot Study

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