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When can we sound the all-clear?

Breast cancer clinicians are familiar with the often-repeated question "When do I get the all-clear Doctor?" from our cancer patients. The question from the patients' point of view is really a simple one: Has the treatment for my breast cancer worked and can I get back to my normal life without worrying about a recurrence of this frightening disease? For clinicians the question really encapsulates one of the greatest limitations of our current technology. Being aware of the natural history of breast cancer with relapses, particular in oestrogen receptor-positive disease, occurring many years after initial therapy, we are unable to answer the question in a satisfactory manner. Patients who may relapse many years later appear to be well and have no clinical or radiological evidence of disease, and yet we know that some patients do harbour dormant disease waiting to progress at some point in the future. We do not know who these patients are, despite advances in our understanding of the biological basis of breast cancer, and at present we cannot detect reliably their dormant disease--if they have it. We also find it extremely difficult to predict when it will recur. Clearly this is a highly unsatisfactory state of affairs since a reliable method for detection of micrometastatic disease would allow those patients free of disease to be reassured that no recurrence would occur in the future and to be discharged from follow-up. Patients with microscopic disease could be offered intensive follow-up or further therapeutic manoeuvres in an attempt to eradicate such micrometastatic disease. Unfortunately, current therapy is given to all patients for the benefit of a few. We cannot tell if it has worked or not, except over a long period of time, and even then late relapses occur.

However, new avenues of research are opening up which may, one day, solve these difficult conundrums. This issue of Advances in Breast Cancer examines some of the new technologies which may, in the very near future, be used to detect microscopic disease and enable us to move into a new era of prognosis, therapy and follow-up.

Goyal et al. examine a new method for detection of tumour DNA within sentinel nodes removed at surgery which does not involve the pathologist! Using polymerase chain reaction technology they discuss a quick and apparently reliable method of real-time assay to detect sentinel axillary lymph node metastases intraoperatively by assessing the homogenate of the nodal tissue. The threshold value for the polymerase chain reaction assay can be set to detect micrometastases or macrometastases and it is commercially available and approved by the FDA and by the European Union. By enabling detection of metastases in lymph nodes in real time during the operation, patients can be spared a second operation, and the method may be applicable to other tumour types such as prostate cancer, melanoma and colorectal cancer.

Another area of great advance is in the detection of micrometastases in the bone marrow of breast cancer patients. Such research has, in fact, been going on for more than 50 years, but it was not until the more recent introduction of antibodies raised against proteins of epithelial origin, confirming the presence of cancer cells within the bone, that the technology has become practical. Rudman et al. discuss the evolution of this technique and the use of the more current methods for detecting circulating tumour cells in the blood of cancer patients. There is even the possibility of detecting the so-called 'cancer stem cell' in bone marrow aspirates or peripheral blood. This will be an active area of research over the next few years in large randomised trials as discussed by Jiao et al. in their article on circulating tumour cells as tumour markers.

In this fast-moving field and with improving technology, it is highly likely that in the future we will have accurate methods of measuring minimal residual disease in our patients, and this could be one of the greatest advances for 20 years, allowing us to reassure patients who have no disease, and treat better those who are not disease free.

Peter Barrett-Lee

Breast Unit, Velindre NHS Trust, Cardiff, UK
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Author:Barrett-Lee, Peter
Publication:Advances in Breast Cancer
Article Type:Editorial
Geographic Code:4EUUK
Date:Sep 1, 2008
Previous Article:Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
Next Article:Real-time RT-PCR for the diagnosis of sentinel lymph node metastasis in breast cancer.

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