Measurement of DKK1 and FRP in breast and prostate cancer patients with bone metastases: Impact of zoledronic acid (ZA)

19659 Background: Bone metastases produce an imbalance in osteoblast and osteoclast activity. While metastases from prostate cancer are osteoblastic, metastases from breast cancer may be osteolytic, osteoblastic or mixed. The wnt/frizzled pathway is involved in maturation of osteoblasts and in adult bone homeostasis. We explored the wnt antagonists dickkopf (DKK1) and frizzled related protein (FRP) as potential biomarkers in bone metastasis after ZA treatment. Methods: This is a pilot cohort study in bisphosphonate naive breast and prostate cancer patients with bone metastases. Cancer therapy was not specified. Patients received 2 monthly doses of ZA 4 mg IV. Pre- and post-treatment (day 60) sera were collected for measurement of FRP and DKK1, along with IL-6, calcium, creatinine and bone-specific alkaline phosphatase (BAP, a marker of osteoblast activity). Primary endpoint: mean change in FRP and DKK1; Secondary endpoints: correlation of biomarkers with each other and comparison of breast vs. prostate cancer patients. Biomarkers were measured using standard ELISA assays. Statistics: comparison of means = student t-test, correlation coefficients = Pearson. Results: Mature data from 14 patients are reported here, 9 with breast and 5 with prostate cancer. Mean age = 61 years (range 42–89). Two breast cancer patients were premenopausal. One prostate and 3 breast cancer patients received chemotherapy; all others were treated hormonally. After ZA, calcium decreased in all patients (p = 0.09). BAP decreased in all but 1 breast and 1 prostate cancer patient (mean decrease 20.0, p = 0.16). IL-6 was undetectable in most patients. FRP decreased in all but 4 patients (mean decrease 6.2, p = 0.13). There was no discernable pattern for DKK1. Pre-treatment DKK1 correlated with FRP (p = 0.01, r2 = 0.39), but there was no correlation post-treatment. Post-treatment DKK1 correlated with both serum calcium (p = 0.04, r2 = 0.49) and BAP (p = 0.005, r2 = 0.65). There was no difference between breast and prostate cancer patients. Conclusions: It is feasible to measure DKK1 and FRP in patients with malignant bone disease. Treatment with ZA has measurable effects upon these and other serum markers. Further studies with more patients are needed to evaluate their potential as biomarkers. No significant financial relationships to disclose.

Download Full-text

Breast cancer patients have better outcomes than prostate cancer patients for palliation of painful bone metastases: Results of RTOG 97–14

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.6073 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 6073-6073

Author(s):

W. F. Hartsell ◽

K. Winter ◽

D. W. Bruner ◽

C. W. Scarantino ◽

R. Ivker ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Bone Metastases ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Painful Bone Metastases

Download Full-text

Prevalence of early-stage prostate and estrogen receptor positive (ER+) breast cancer patients receiving primary androgen deprivation therapy (ADT) and aromatase inhibitors (AIs) in the United States (U.S.)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e22126 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e22126-e22126

Author(s):

A. Barlev ◽

M. Yong ◽

G. Cherkowski ◽

K. Cetin ◽

J. Fryzek

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Clinical Practice ◽

Hormone Therapy ◽

Cancer Patients ◽

Early Stage ◽

Breast Cancer Patients ◽

Claims Database ◽

Breast And Prostate Cancer ◽

The U.S

e22126 Background: AIs and ADT are used to prevent recurrence of breast and prostate cancers but have been shown to accelerate bone loss. We estimated the prevalence of early-stage ER+ breast and prostate cancer patients on hormone therapy in the U.S., as this is not well-described in the literature. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) Program, published literature, clinical practice, and a large claims database were used. We began with the American Cancer Society's estimated number of new breast and prostate cancer cases for the year 2008. We then assessed the number of patients with localized/regional disease and ER+ tumors and those receiving primary ADT (both chemical and surgical) or AI therapy by applying proportions from SEER, published literature, clinical practice, and the claims database. Using these incident case counts, we calculated the 5-year prevalence using appropriate cohort-specific survival rates to sum the number of new and surviving cases over a 5-year period. Results: The estimated 5-year prevalence of early-stage ER+ breast cancer for women aged ≥50 years in the U.S. was 607,411, of which 293,904 (48.4%) were on AI therapy based on the claims database. However, because this data source was limited to women aged <65 years, we also used estimates from clinical practice to capture AI use for women of all ages. Based on clinical practice, 402,637 (66.3%) to 460,156 (75.8%) of early-stage ER+ breast cancer patients were on AI therapy. For early-stage prostate cancer, the estimated 5-year prevalence for all ages was 1,024,238, of which 141,451 (13.8%) were on primary ADT. However, these figures may underestimate current usage of hormone therapies, as our data and the literature show increasing trends in ADT and AI use for early-stage disease. Conclusions: Based on a combination of population-based data and the published literature, approximately half of all early-stage ER+ breast cancer patients and a modest proportion of early-stage prostate cancer patients are on hormone therapy in the U.S. [Table: see text]

Download Full-text

Prospective comparison of the diagnostic accuracy of 18F-FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients

European Radiology ◽

10.1007/s00330-021-07956-0 ◽

2021 ◽

Author(s):

Nils Martin Bruckmann ◽

Julian Kirchner ◽

Lale Umutlu ◽

Wolfgang Peter Fendler ◽

Robert Seifert ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastases ◽

Cancer Patients ◽

Bone Scintigraphy ◽

Fdg Pet ◽

Primary Breast Cancer ◽

Whole Body ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Initial Staging

Abstract Objectives To compare the diagnostic performance of [18F]FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients. Material and methods A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body [18F]FDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar χ2 test was performed to compare sensitivity and specificity between the modalities. Results Forty-one bone metastases were present in 7/154 patients (4.5%). Both [18F]FDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (p < 0.01, difference 43.9%) and bone scintigraphy (p < 0.01, difference 63.4%). Conclusion [18F]FDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases. Key Points • [18F]FDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. • Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients.

Download Full-text

Correlation between ER, PR, HER-2, and Ki-67 with the risk of bone metastases detected by bone scintigraphy in breast cancer patients: A cross sectional study

Annals of Medicine and Surgery ◽

10.1016/j.amsu.2021.102532 ◽

2021 ◽

pp. 102532

Author(s):

Hanif Afkari ◽

Firdian Makrufardi ◽

Basuki Hidayat ◽

Hendra Budiawan ◽

Achmad Hussein Sundawa Kartamihardja

Keyword(s):

Breast Cancer ◽

Bone Metastases ◽

Cancer Patients ◽

Bone Scintigraphy ◽

Cross Sectional Study ◽

Breast Cancer Patients ◽

Sectional Study ◽

Ki 67 ◽

Cross Sectional ◽

Her 2

Download Full-text

Surgery for primary tumor benefits survival for breast cancer patients with bone metastases: a large cohort retrospective study

BMC Cancer ◽

10.1186/s12885-021-07964-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhangheng Huang ◽

Xin Zhou ◽

Yuexin Tong ◽

Lujian Zhu ◽

Ruhan Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Bone Metastases ◽

Cancer Patients ◽

Primary Tumor ◽

Predictive Accuracy ◽

Rank Test ◽

Breast Cancer Patients ◽

Risk Of Death ◽

The Impact

Abstract Background The role of surgery for the primary tumor in breast cancer patients with bone metastases (BM) remains unclear. The purpose of this study was to determine the impact of surgery for the primary tumor in breast cancer patients with BM and to develop prognostic nomograms to predict the overall survival (OS) of breast cancer patients with BM. Methods A total of 3956 breast cancer patients with BM from the Surveillance, Epidemiology, and End Results database between 2010 and 2016 were included. Propensity score matching (PSM) was used to eliminate the bias between the surgery and non-surgery groups. The Kaplan-Meier analysis and the log-rank test were performed to compare the OS between two groups. Cox proportional risk regression models were used to identify independent prognostic factors. Two nomograms were constructed for predicting the OS of patients in the surgery and non-surgery groups, respectively. In addition, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to evaluate the performance of nomograms. Result The survival analysis showed that the surgery of the primary tumor significantly improved the OS for breast cancer patients with BM. Based on independent prognostic factors, separate nomograms were constructed for the surgery and non-surgery groups. The calibration and ROC curves of these nomograms indicated that both two models have high predictive accuracy, with the area under the curve values ≥0.700 on both the training and validation cohorts. Moreover, DCA showed that nomograms have strong clinical utility. Based on the results of the X-tile analysis, all patients were classified in the low-risk-of-death subgroup had a better prognosis. Conclusion The surgery of the primary tumor may provide survival benefits for breast cancer patients with BM. Furthermore, these prognostic nomograms we constructed may be used as a tool to accurately assess the long-term prognosis of patients and help clinicians to develop individualized treatment strategies.

Download Full-text

Lesion-Based Bone Metastasis Detection in Chest Bone Scintigraphy Images of Prostate Cancer Patients Using Pre-Train, Negative Mining, and Deep Learning

Diagnostics ◽

10.3390/diagnostics11030518 ◽

2021 ◽

Vol 11 (3) ◽

pp. 518

Author(s):

Da-Chuan Cheng ◽

Te-Chun Hsieh ◽

Kuo-Yang Yen ◽

Chia-Hung Kao

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Deep Learning ◽

Bone Metastasis ◽

Cancer Patients ◽

Bone Scintigraphy ◽

Breast Cancer Patients ◽

Location Detection ◽

The Mean ◽

Mean Sensitivity

This study aimed to explore efficient ways to diagnose bone metastasis early using bone scintigraphy images through negative mining, pre-training, the convolutional neural network, and deep learning. We studied 205 prostate cancer patients and 371 breast cancer patients and used bone scintigraphy data from breast cancer patients to pre-train a YOLO v4 with a false-positive reduction strategy. With the pre-trained model, transferred learning was applied to prostate cancer patients to build a model to detect and identify metastasis locations using bone scintigraphy. Ten-fold cross validation was conducted. The mean sensitivity and precision rates for bone metastasis location detection and classification (lesion-based) in the chests of prostate patients were 0.72 ± 0.04 and 0.90 ± 0.04, respectively. The mean sensitivity and specificity rates for bone metastasis classification (patient-based) in the chests of prostate patients were 0.94 ± 0.09 and 0.92 ± 0.09, respectively. The developed system has the potential to provide pre-diagnostic reports to aid in physicians’ final decisions.

Download Full-text