High tumour immune cell levels may help screen HER2-positive breast cancer patients for chemo

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Published: 12 Dec 2014
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Dr Edith Perez - Mayo Clinic, Rochester, USA

Dr Perez talks to ecancertv at SABCS 2014 about her research which found that women with HER2-positive breast cancer who had high levels of immune cells in their tumours had a decreased risk of cancer recurrence after treatment with chemotherapy alone compared with their counterparts who had low levels of tumour-infiltrating immune cells.

Read the news story for more.


You’re looking at stromal tumour infiltrating lymphocytes, S-TILs; what were you doing this for in the context of HER2 positive breast cancer?

We have been very interested in identifying predictive or prognostic markers for patient management over the last several years. So this is one of several studies we have conducted. Over the last few years we’ve become more and more interested in the potential that the immune system itself has something to do with response to therapy. This study that we presented here at San Antonio addresses this issue.

What do the TILs normally do?

When a patient develops a tumour the body tries to react to that tumour. So the body essentially can send TILs, or tumour infiltrating lymphocytes, to either try to kill the tumour or actually stimulate the growth of the tumour. So our idea was to determine if the number of these tumour infiltrating lymphocytes could be correlated to the benefit of therapy.

And the therapy in question could either be chemotherapy or it could be trastuzumab or perhaps both?

That is right, so we tested both possibilities. When the patients received chemotherapy alone or when the patients received chemotherapy in combination with trastuzumab which is now the standard of care.

What did you find with relation to the TILs?

Our results were very interesting and actually rather surprising to us and to the medical community in general. We found that increasing levels of TILs was associated with increased benefit to chemotherapy but we also found that increasing levels of TILs were not correlated with increasing benefit to the addition of trastuzumab. In other words, if a patient’s tumour had very high levels of these TILs we could not demonstrate that there was a clear benefit for adding trastuzumab.

So you might have thought that because TILs are an immune factor they might be correlated with the molecular approach and in fact that wasn’t the case?

Yes, very good point because in our group we have actually looked at other molecular aspects of these tumour specimens and in the next few months that is exactly what we are going to do – correlate our gene profiles with the observation of the number of TILs.

I think I calculated something like a hazard ratio of 0.2. What does that figure mean and where does it come in?

Yes, it means that there’s that degree of benefit for the use of chemotherapy in the patients with the high lymphocytic infiltrate. We have definite evidence, based on the data from our study, that there is an association between high numbers of TILs and benefit to chemotherapy, very impressive.

And you had 945 patients so you’re sure of what you’re saying.

The data are quite solid from the statistical standpoint.

What then are the clinical recommendations that you’d pass on to doctors at this point?

There are some clinical implications for this data and they include the following. Number one, pathologists need to be aware that we, in medical oncology, are starting to pay attention to the number of lymphocytes in the tumour as potential markers of patient outcome. We have been involved in the development of international guidelines to quantify TILs so this material is now available to all physicians to read. Third, it’s a little bit too early to say that patients with high numbers of TILs should not receive trastuzumab but we need to do additional studies in other tumour specimens to validate the findings that we reported in N9831.

Do you think the TILs could find themselves implicated in other aspects of cancer therapy in the future soon?

Yes, I think TILs theoretically could be utilised if we can determine what types of TILs they are. Are they TILs that are trying to enhance tumour growth? Are they TILs that are trying to kill tumour growth? And if that’s the case then we can attempt to do something to modulate the amount of TILs in the tumour area then potentially change the sensitivity to different treatments.

I can’t resist asking you which things, because there are quite a few immune manipulations around at the moment, aren’t there?

That is absolutely right. So there are many potential types of cells that may be there and there are also several ways to modulate the immune system. So our group is very interested in those two areas and we already have studies planned to address those two issues.

So from this particular study that you’ve just reported, what would you boil down out of this as a few words to say to doctors to remember?

High levels of tumour infiltrating lymphocytes are associated with high benefit of systemic chemotherapy in patients with early stage HER2 positive breast cancer. Patients who have high levels of tumour infiltrating lymphocytes at this time have an unclear benefit from the addition of trastuzumab.