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Metastatic breast cancer blood test performs well

Thursday 14 March 2013

A blood test to see how well women are responding to breast cancer treatment could be on its way, The Daily Telegraph reports. It describes the test as a ‘liquid biopsy’.

The Telegraph reports on a small US study that compared tests designed to monitor the size of metastatic breast cancer. Metastatic breast cancer is cancer that has spread out of breast tissue and into other parts of the body. It is currently incurable but can be controlled with treatment in an attempt to prolong survival.

This study looked at a new blood test designed to detect fragments of tumour DNA in the blood, to see if it could accurately assess how well women were responding to chemotherapy.

The study found that the level of fragments of tumour DNA in the blood of these women corresponded well with the level of disease as shown by CT scans. It found that the results of this blood test were more accurate than other blood tests looking at other biological markers of cancer.

These results are encouraging, but more research on larger groups of women is needed to see what role the test could have, and how it could supplement or improve monitoring using scans.

At present it is not possible to say whether the new test would have any impact on the treatment of metastatic breast cancer, or whether it would have any effect on important outcomes, such as survival. These things would need to be considered through further research to establish whether the blood test could become widely available as the media suggests.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and the Cancer Research UK Cambridge Institute, and other institutions in the US. It was funded by Cancer Research UK among other resources.

The study was published in the peer-reviewed New England Journal of Medicine, and has been made freely available to download (open access).

The reporting of this study by both the Telegraph and the Daily Mail is too optimistic. They base their estimates of the test’s availability on the understandably enthusiastic comments of one of the researchers.

The test, which is still at the experimental stage, aims to monitor how well metastatic breast cancer (that is, cancer that has already spread to other parts of the body) is responding to chemotherapy. It is not known whether or how soon the test will become available for use in clinical practice.

It also does not apply to all breast cancer or to cancer in general, as the newspapers suggest.

Perhaps most importantly, there is nothing to suggest from the current study that using this biological marker to measure tumour response could save ‘thousands of lives’ as suggested in the Mail’s article.

Currently, metastatic breast cancer cannot be cured. The goal of treatment is to slow the spread of the cancer and try to maintain quality of life. This new test may help to supplement scans to monitor how the disease is progressing, but it is currently difficult to see how it could save lives.

What kind of research was this?

This was a study in women with metastatic breast cancer who were being treated with chemotherapy at a single centre in the US. Researchers assessed the women using different tests to see how the disease was progressing. The women all had radiological (CT scan) images of the breast tumours, in addition to having blood tests to:

  • look at levels of a particular protein in the blood (CA 15-3) that has previously been shown to be raised in metastatic breast cancer
  • look at DNA from the tumour that was circulating in the blood
  • look at the number of tumour cells circulating in the blood

The researchers say that the best way to manage metastatic breast cancer is to monitor how the tumour responds to treatment. They say that the tumour marker CA 15-3 has been extensively studied, but there is a need to find improved tumour “markers” to assess the level of tumour in the body. Measuring levels of tumour DNA fragments in the blood has not been so widely investigated.

This study aimed to compare radiological imaging (the ‘gold standard’ non-invasive method of looking for tumours) with measuring CA 15-3 and with measuring DNA fragments in the blood.

What did the research involve?

The researchers recruited a total of 52 women who were undergoing treatment for metastatic breast cancer at the study centre and were eligible for the study.

Laboratory methods were first used to study the DNA sequence within the cells of breast cancer tissue specimens from the women, and to see which women had particular mutations or variations in the DNA that could be looked for in the blood.

The researchers needed to identify DNA changes that were present in the tumour cells but not in the women’s normal cells. Thirty of the women were found to have suitable tumour-specific DNA sequences. Researchers took blood samples from these women at intervals of around three weeks over a two-year period.

The women’s blood samples were measured for the DNA fragments, for CA 15-3 levels and for any circulating tumour cells (one or more tumour cells per 7.5ml of blood). The women were also monitored with CT scans.

The researchers looked at how well the different tumour markers (CA 15-3, circulating tumour DNA fragments and tumour cells) related to the change in ‘tumour burden’ (the total size of cancerous cells inside the body as judged by CT scan) of the women over time in response to their treatment.

What were the basic results?

Of the 30 women with suitable DNA sequences for testing, circulating tumour DNA fragments were detected in 29 (97%). The one woman in whom tumour DNA fragments were not detected had a ‘low burden’ of metastatic disease (that is, she had only a small volume of enlargement of certain lymph nodes in her chest) and her disease did not progress during the study.

Circulating DNA fragments were detected in 115 of the 141 blood samples (82%) tested. Data allowing comparison of CA 15-3 levels with circulating tumour DNA fragments were available for 114 blood samples from 27 women.

CA 15-3 could be detected in 21 of these women (78%) and in 71 of the 114 blood samples (62%). By contrast, DNA fragments could be detected in 26 of these 27 women (96%) and in 94 of 114 blood samples (82%). Of the 43 blood samples without elevated CA 15-3 levels, 27 (63%) had measurable levels of tumour DNA.

Circulating tumour cells could be detected at one or more time points in 26 of 30 women (87%). Of 126 blood samples tested, 50 (40%) had no detected circulating tumour cells, 76 (60%) had levels above one or more cells per 7.5ml of blood and 46 (37%) had levels above five or more cells per 7.5ml.

In comparison, tumour DNA fragments were detected in 29 of the 30 women (97%) and in 106 of 126 samples (84%).

The researchers found that, compared with measuring CA 15-3 or circulating tumour cells, measuring tumour DNA fragments showed the most consistent relationship with changes in tumour burden, as identified on CT imaging. Progressive disease was demonstrated on CT in 19 women during the study and this corresponded with increases in DNA fragments in 17 of them.

How did the researchers interpret the results?

The researchers describe their study as a ‘proof-of-concept analysis’ that shows that looking at fragments of tumour DNA circulating in the blood is an informative and highly sensitive biological marker of metastatic breast cancer.


This is valuable research looking at different biological markers of metastatic breast cancer and how well they reflect changes in the burden of disease.

The study in 30 women who were receiving chemotherapy found that looking for fragments of tumour DNA in the blood of these women corresponded well with the level of disease as shown by CT imaging.

Looking for tumour DNA fragments also showed better correlation with disease than looking for a different tumour marker of metastatic breast cancer (CA 15-3) or looking for tumour cells circulating in the blood.

The study will need to be followed by research in larger numbers of women with metastatic breast cancer to see what complementary role this test may have alongside standard radiological imaging. If further research provides positive results, it could be a useful tool for assessing disease progression and how well a woman is responding to treatment.

This test is still at the research stage and it is not possible at the current time to say when – and if – the blood test will be used in real clinical practice. It is also not possible to say whether the test will help doctors to prolong, improve or save lives, as the newspapers suggest.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Blood test shows if breast cancer therapy is working and allow treatment to be tailored to each individual sufferer

Daily Mail, 14 March 2013

Cancer blood test 'on NHS in two years'

The Daily Telegraph, 13 March 2013

Links to the science

Dawson SJ, Tsui DWY, Murtaza M, et al.

Analysis of Circulating Tumor DNA to Monitor Metastatic Breast Cancer

The New England Journal of Medicine. Published online March 13 2013