Breast Cancer: Early diagnosis using materials immortalisation

在英国，每年有55000新确诊的乳腺癌病例(全世界有170万例)，英国每年因乳腺癌而付出的经济代价是15亿英镑。早期和准确的诊断对于最有效的治疗和降低成本至关重要。目前的诊断不足的特点是：(I)乳房X光摄影的假阳性率为80%，(Ii)某些乳腺癌的过度治疗，以及(Iii)不明确的组织病理学导致不确定的预后。这一建议将产生对受累组织的物理化学的新的理解，并因此将确定潜在的新的生物标志物和诊断方法。我们将采用一种新的、多学科的方法进行疾病诊断，并将资深临床医生的专业知识与材料科学家结合起来研究组织物理化学。我们还将利用一种独特的、回溯性的抽样方法，使我们能够获得前所未有的患者数量。这项工作的成功结果将对了解疾病和发展准确的乳腺癌诊断产生重大影响。乳腺组织内的钙化被用作恶性肿瘤的主要标志，尽管生物来源的钙化的沉淀机制仍然存在相当大的争议。相比之下，磷灰石在降水时吸收外来环境离子的能力是毋庸置疑的。因此，形成点的组织生理学的化学特征在钙化过程中变得不朽。体内钙化相的沉淀是由组织化学的轻微改变引发的，对于乳房组织来说，这发生在癌症的一开始。因此，我们的主要假设是，磷灰石钙化的物理化学特征可能被用作癌症的新生物标志物。该项目的主要目的是确定和了解乳腺组织钙化的基础物理化学特征，以便将来能够开发出体内准确的诊断探针。该项目将(A)确定代表多种肿瘤亚型的存档标本群用于材料分析，(B)开发高分辨率钙化表征的尖端物理方法，以及(C)将钙化物理化学与临床诊断和预后联系起来。这项工作的成功结果将对了解疾病和发展准确的乳腺癌诊断产生重大影响。

Within the UK there are >55000 new cases of breast cancer diagnosed every year (world-wide >1.7 million) and the economic cost of breast cancer to the UK is >£1.5bn per annum. Early and accurate diagnoses are critical for the most effective treatments and reduced costs. Current diagnostic inadequacies are characterised by (i) an >80% false positive rate for mammography, (ii) significant overtreatment of some breast cancers, and, (iii) equivocal histopathology leading to uncertain prognoses.This proposal will generate a new understanding of the physicochemistry of involved tissues and, as a result, will identify potential new biomarkers and diagnostic methods. We will adopt a new, multidisciplinary approach to disease diagnosis, and combine the expertise of senior clinicians with material scientists to study tissue physicochemistry. We will also exploit a distinct, retrospective approach to sampling that will enable access to unprecedented patient numbers. Successful outcomes from this work will have significant impacts for understanding disease and development of accurate breast cancer diagnostics.Calcifications within breast tissues are used as a primary marker of malignancy although the precipitation mechanism of biologically derived calcifications remains a matter of considerable debate. In contrast, the capacity of apatites to incorporate 'foreign', environmental ions at the time of precipitation is incontrovertible. Thus chemical features of tissue physiology at the point of formation become immortalised within calcifications. Precipitation of calcific phases in vivo is triggered by slight modifications to tissue chemistry and this, in the case of breast tissue, occurs at the very onset of the cancer.Our primary hypothesis then is that apatite calcification physicochemical characteristics may be employed as novel biomarkers of cancer. The primary aim of this project is to determine and understand the underpinning physicochemical characteristics of breast tissue calcifications to enable future development of in vivo, accurate diagnostic probes. The project will (a) identify archived specimen populations representing a wide range of tumour subtypes for material analyses, (b) exploit cutting edge physical methods of high resolution calcification characterisation and, (c) relate calcification physicochemistry to clinical diagnosis and prognosis.Successful outcomes from this work will have significant impacts for understanding disease and development of accurate breast cancer diagnostics.