Measurement of urinary collagen cross-links indicate response to therapy in patients with breast cancer and bone metastases

Objective assessment of response in bone metastases from breast cancer using radiological techniques takes up to 6 months of treatment to be certain of a response, and sclerotic metastases are not evaluable. Standard serum and urinary tumour markers may not always be utilized to predict response, as they may not be elevated, and therefore may not change on treatment. The development of the urinary pyridinoline cross-link assays which measure mature bone breakdown products have been shown to be highly sensitive and specific as a measure of bone change in osteoporosis. We have measured pyridinoline (Pyr) and deoxypyridinoline (Dpyr) cross-links sequentially in 36 breast cancer patients with bone metastases, to determine if the measurement of these analytes predicts response at an earlier stage than radiological assessment. Response was assessed by UICC criteria. Seventeen women responded to hormonal therapy, whilst 19 developed progressive disease. Both Pyr and Dpyr increased sequentially in women with progressive disease with changes becoming apparent by 8 weeks (P < 0.03). In responding women, cross-link levels did not change significantly. Pyr and Dpyr were more sensitive and specific than the standard serum tumour marker CA 15-3. Urinary cross-link measurements provide a novel objective method of assessing response to treatment in women with bone metastases. Initial elevated urinary cross-link markers identify patients who tend not to respond to changes in hormonal therap

Cellular mechanisms of bone resorption in breast carcinoma

The cellular mechanisms that account for the increase in osteoclast numbers and bone resorption in skeletal breast cancer metastasis are unclear. Osteoclasts are marrow-derived cells which form by fusion of mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have determined whether circulating osteoclast precursors are increased in number or have an increased sensitivity to humoral factors for osteoclastogenesis in breast cancer patients with skeletal metastases (± hypercalcaemia) compared to patients with primary breast cancer and age-matched normal controls. Monocytes were isolated and cocultured with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D3[1,25(OH)2D3] and human macrophage colony stimulating factor (M-CSF) on coverslips and dentine slices. Limiting dilution experiments showed that there was no increase in the number of circulating osteoclast precursors in breast cancer patients with skeletal metastases (± hypercalcaemia) compared to controls. Osteoclast precursors in these patients also did not exhibit increased sensitivity to 1,25(OH)2D3 or M-CSF in terms of osteoclast formation. The addition of parathyroid hormone-related protein and interleukin-6 did not increase osteoclast formation. The addition of the supernatant of cultured breast cancer cell lines (MCF-7 and MDA-MB-435), however, significantly increased monocyte-osteoclast formation in a dose-dependent fashion. These results indicate that the increase in osteoclast formation in breast cancer is not due to an increase in the number/nature of circulating osteoclast precursors. They also suggest that tumour cells promote osteoclast formation in the bone microenvironment by secreting soluble osteoclastogenic factor(s). © 2001 Cancer Research Campaign http://www.bjcancer.co

A Review on the Mechanical Modeling of Composite Manufacturing Processes

© 2016, The Author(s). The increased usage of fiber reinforced polymer composites in load bearing applications requires a detailed understanding of the process induced residual stresses and their effect on the shape distortions. This is utmost necessary in order to have more reliable composite manufacturing since the residual stresses alter the internal stress level of the composite part during the service life and the residual shape distortions may lead to not meeting the desired geometrical tolerances. The occurrence of residual stresses during the manufacturing process inherently contains diverse interactions between the involved physical phenomena mainly related to material flow, heat transfer and polymerization or crystallization. Development of numerical process models is required for virtual design and optimization of the composite manufacturing process which avoids the expensive trial-and-error based approaches. The process models as well as applications focusing on the prediction of residual stresses and shape distortions taking place in composite manufacturing are discussed in this study. The applications on both thermoset and thermoplastic based composites are reviewed in detail

Adjuvant treatment for breast cancer

Adjuvant treatment for breast cancer is given following primary surgical management and aims to reduce the risk of recurrence (both local and distant) as well as improve survival rates. Radiotherapy is delivered to reduce local recurrence risk. Whole breast radiotherapy is considered standard treatment following breast-conserving surgery for invasive cancer and is also considered after mastectomy depending on pathological risk factors. Systemic therapies (such as chemotherapy, endocrine treatment and biological therapy) reduce the risk of distant metastases and improve overall survival. The decision to advise adjuvant treatment is complex (taking into account both prognostic and patient factors) and is made with the patient following a multidisciplinary team meeting. It is now common practice to employ benefit-risk calculators in the clinical setting to aid treatment decision making. Recent major advances in both systemic treatments and radiotherapy techniques have led to more personalized treatment for patients with the aim to reduce breast cancer mortality even further

Adjuvant treatment for breast cancer

Adjuvant treatment for breast cancer is given following primary surgical management and aims to reduce the risk of recurrence (both local and distant) as well as improve survival rates. Radiotherapy is delivered to reduce local recurrence risk. Whole breast radiotherapy is considered standard treatment following breast-conserving surgery for invasive cancer and is also considered after mastectomy depending on pathological risk factors. Systemic therapies (such as chemotherapy, endocrine treatment and biological therapy) reduce the risk of distant metastases and improve overall survival. The decision to advise adjuvant treatment is complex (taking into account both prognostic and patient factors) and is made with the patient following a multidisciplinary team meeting. It is now common practice to employ benefit-risk calculators in the clinical setting to aid treatment decision making. Recent major advances in both systemic treatments and radiotherapy techniques have led to more personalized treatment for patients with the aim to reduce breast cancer mortality even further

Breast tumour volume and blood flow measured by MRI after one cycle of epirubicin and cyclophosphamide-based neoadjuvant chemotherapy as predictors of pathological response.

Objectives: Better markers of early response to neoadjuvant chemotherapy (NACT) in patients with breast cancer are required to enable the timely identification of non-responders and reduce unnecessary treatment side-effects. Early functional imaging may better predict response to treatment than conventional measures of tumour size. The purpose of this study was to test the hypothesis that the change in tumour blood flow after one cycle of NACT would predict pathological response. Methods: In this prospective cohort study, dynamic contrast-enhanced MRI was performed in 35 females with breast cancer before and after one cycle of epirubicin and cyclophosphamide-based NACT (EC90). Estimates of tumour blood flow and tumour volume were compared with pathological response obtained at surgery following completion of NACT. Results: Tumour blood flow at baseline (mean ± SD; 0.32 ± 0.17 ml/min/ml) reduced slightly after one cycle of NACT (0.28 ± 0.18 ml/min/ml). Following treatment 15 patients were identified as pathological responders and 20 as non-responders. There were no relationships found between tumour blood flow and pathological response. Conversely, tumour volume was found to be a good predictor of pathological response (smaller tumours did better) at both baseline (area under the receiver operating characteristic curve 0.80) and after one cycle of NACT (area under the receiver operating characteristic curve 0.81). Conclusion & advances in knowledge: The change in breast tumour blood flow following one cycle of EC90 did not predict pathological response. Tumour volume may be a better early marker of response with such agents