A new US study could help improve the use of targeted therapy for this type of breast cancer. We discuss the research and what benefits it could offer to patients.

Friday 23 January 2015      Research blog
Drug trial reduces risk of recurrence in early-stage HER2-positive patients

Results from a study in the US suggest that a new treatment regime could dramatically reduce the risk of recurrence (the chance that the cancer comes back after treatment) in some HER2-positive breast cancer patients. The study, led by Professor Eric Winer at the Dana-Farber Cancer Institute and published in the New England Journal of Medicine, could help improve the use of targeted therapy for this type of breast cancer. 

HER2-positive breast cancer: background

HER2-positive breast cancer is a type of breast cancer where the tumour cells carry much more of the HER2 protein than normal, healthy breast cells.  HER2 helps relay communication signals through the cell which tell it to divide.  It also prevents the cell from going through a process called ‘apoptosis’, where the cell commits suicide should things get out of control.  This combination of promoting cell division and preventing cell death contributes to the growth of HER2-positive tumours.

Somewhere between 15-25% of all breast cancers are HER2-positive and these patients tend to be at a higher risk of recurrence following treatment.  Patients are tested to see if their tumour is HER2-positive or not prior to treatment so that the best treatment can be selected for them.  The drug Herceptin has revolutionised treatment for this type of breast cancer because it specifically targets the HER2 protein, effectively shutting off the signals telling the cells to grow.

However, as with many effective cancer drugs, some patients have or develop resistance to Herceptin and as such are at high risk of their cancer recurring.  Research is ongoing to improve how drugs like Herceptin are used. This new study could be a significant step forward in reducing recurrence for these patients.

Combining drugs

The study set out to investigate the use of Herceptin combined with a low-dose of the chemotherapy drug, paclitaxel, for the treatment of early stage HER2-positive breast cancer patients whose cancer had not yet spread to the lymph nodes

No standard of care with Herceptin exists for these patients because they are often excluded from clinical trials due to their small tumour size.  Although their risk of recurrence is lower than patients whose cancer has spread to the lymph nodes, this group of HER2-positive patients are still at risk, so this trial sought to provide evidence for a single, standard treatment for this group of patients.

The results

Just over 400 patients received the combination therapy post-surgery, receiving both drugs for 12 weeks, followed by nine months of Herceptin on its own.  The researchers followed the patients for three to four years after treatment to assess the rate of recurrence.  They found that the nearly 99% of patients were recurrence free when followed up three years later.  Importantly, the number of serious toxic side effects was also low in these patients.

Although the follow up period is quite short, these results are still promising.  For this specific group of HER2-positive patients it may now be clearer exactly what treatment regime works best.  Normally these patients would receive treatment with Herceptin plus an additional two or three chemotherapy drugs which often causes substantial toxic side effects. It’s promising, then, that using a lower dose of one chemotherapy with Herceptin can sufficiently reduce these side effects whilst offering a high level of protection from recurrence.

No control

The keen eyed amongst you may have noticed that this study doesn’t involve a ‘control’ group.  This would be a group of patients not receiving either Herceptin or paclitaxel to which the results from the treatment group could be compared to.  It’s most likely that this is because it may be deemed unethical to not treat HER2-positive patients with Herceptin when we know how effective it can be.  There is also not a great deal of evidence that Herceptin on its own is effective in these patients so it’s not recommended that treatment regimens without at least one chemotherapy are offered.

Making the most out of drugs

A lot of emphasis is put on understanding the biological characteristics of a patient’s tumour to guide treatment.  This has had a big impact on outcomes for breast cancer patients but it’s important that other factors are also taken into account when making decisions about treatment.  This study highlights how looking at the size, stage and molecular characteristics of patients can improve the effectiveness of treatment.

Herceptin has had a huge impact on the treatment of breast cancer and it’s unlikely that a better targeted treatment will ever be designed.  Research such as this ensures that we make the most out of these drugs so that everyone receives the greatest amount of benefit possible.

Dr Matthew Lam is Breakthrough Breast Cancer's Senior Research Officer