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Breast cancer 'changes' as it spreads

Wednesday 4 November 2009

Research has found that “nearly 40% of breast cancer tumours change form when they spread,” BBC News reported. It said that the finding could mean cancer patients may need changes to their treatment regime.

This research found that some tumours changed the type of proteins they produced when they spread from the breast to the lymph nodes (the area of the body where breast cancer often spreads first). As tumours are more likely to respond to certain treatments depending on which proteins they produce, such changes may have an impact on the effectiveness of some treatments.

However, the study contained relatively few cancer patients with certain types of tumour and it could not assess the effect of the changes on treatment. As such, the results will need to be verified by further research involving more patients and which examines whether the outcome of treatment is affected.

It is too early to know whether reassessing the characteristics of breast cancer tumours that have spread to the lymph nodes would help choose more effective treatment.

Where did the story come from?

The research was carried out by Dr S J Aitken and colleagues from the Breakthrough Research Unit at the University of Edinburgh. It was funded by Breakthrough Breast Cancer, the Scottish Funding Council and Cancer Research UK. The study was published in the peer-reviewed medical journal Annals of Oncology .

In general, the BBC gave a balanced report of this research. It notes that “a clinical trial needs to be carried out to fully evaluate the benefits of testing cancer cells in the lymph nodes before it can be approved for use on the NHS.”

What kind of research was this?

This was a laboratory study that looked at tissue taken from patients with invasive breast cancer. The researchers tested whether certain proteins in breast cancer cells change over time as the cancer spreads. They propose that these changes could affect how tumours respond to treatment.

The proteins in which they were interested were the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The presence or absence of these proteins predicts how well tumours respond to certain non-surgical treatments (called adjuvant treatments). For example, tumours that produce the ER protein are more likely to be susceptible to hormone treatments such as tamoxifen.

These proteins are routinely tested for in breast cancer so that the appropriate treatment can be identified. However, at present it is not known if the proteins that the cancer produces change as the cancer spreads from the breast. If so, this could be one explanation for why treatments sometimes fail.

What did the research involve?

The researchers took breast tissue collected from 385 women who had surgery to remove invasive breast cancers between 1999 and 2002. When breast cancers spread, they often spread to the lymph nodes first. The researchers also had lymph node tissue from 211 of these women in whom the cancer had spread to the lymph nodes.

The researchers used biochemical techniques to measure the levels of ER, PR and HER2 proteins in the tissues they collected. The main technique used antibodies to attach fluorescent chemicals to these proteins. By measuring the level of fluorescence a tissue gave off, the researchers estimated how much of each protein there was.

Tissue that contains more than a certain level of a protein is considered “positive” for that receptor. If it contains less, it is “negative”. The researchers compared the breast and lymph node tissue from individual women to see if these tissues differed in whether they were positive or negative for ER, PR and HER2 proteins.

What were the basic results?

The researchers found that, in just under half (46.9%) of the women tested, the status of at least one of the three receptor proteins changed, either from positive to negative or vice versa:

  • 28.4% of women’s tumours changed their ER status.
  • 23.5% of women’s tumours changed their PR status.
  • 8.9% of women’s tumours changed their HER2 status.

In about 15% of cases, the levels of ER or PR proteins changed fivefold or more. Nine of the 39 (23.1%) breast tumours that were negative for all three proteins became positive for one or more of these proteins when the cancer spread to the lymph nodes.

How did the researchers interpret the results?

The researchers concluded that a significant proportion of breast cancer tumours show changes in their production of ER, PR or HER2 proteins when they spread to the lymph nodes. They suggest that testing for these proteins in cancerous lymph nodes “could be a more accurate measurement for guiding adjuvant therapy”, but that this “requires testing in a clinical trial”.


This study reports that the characteristics of breast tumours may change as they spread through the body. It gives further insight into the behaviour of cancer cells, but its findings will require confirmation in other studies.  Other points of note are:

  • Although the study included samples from a relatively large number of women, comparatively few had certain characteristics (for example, those who tested negative for all three proteins). As such, the findings will need to be confirmed by other studies.
  • The study only looked at lymph node metastases (spread). It cannot show what happens when the cancerous cells spread further throughout the body.
  • Although the findings provide a possible reason why cancer treatments may fail, as the researchers report, their study was too small to look at whether these changes predict treatment failure. Further studies will be needed to assess whether this is the case.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Breast cancer changes with spread.

BBC News, 4 November 2009

Links to the science

Aitken SJ, Thomas JS, Langdon SP, Harrison DJ and Faratian D.

Quantitative analysis of changes in ER, PR and HER2 expression in primary breast cancer and paired nodal metastases.

Annals of Oncology 2009, first published online on October 25