You’ve been looking at male breast cancer and you’ve got a very, very big study with a lot of patients in it. Can you tell me what it is that you did?
Indeed. This is called the International Male Breast Cancer Programme and it’s a worldwide effort to try to characterise this very rare disease. So male breast cancer accounts for only 1% of all breast cancers and so far we have very little knowledge of the disease and patients are managed as an extrapolation of female breast cancer.
Can you give me the back story on just how patients are managed normally? Because there aren’t enough of them for individual centres to really have a lot of expertise.
Not only that but since no prospective randomised study was ever finished because of lack of accrual we actually do not have solid data on how to manage this disease. So this programme basically is set out to understand the biology of the disease, to understand how we could better manage these patients and at the same time review what has been done in the last twenty years.
So what did you do?
For the first part of the programme we had a joint retrospective analysis of all patients treated in the last twenty years in the participating institutions. We ended up having 1,800 eligible patients and those patients had to have a tumour block and that tumour block was centrally assessed. So now we have not just the clinical data centrally collected and analysed but also the biology centrally analysed.
What did you find?
In terms of the clinical data we found that overall patients have not been, let’s say, correctly managed. So not just related to surgery, the vast majority has mastectomy although about 40-50% have small tumours but still there is no tradition of discussing with the patient the possibility of breast conserving surgery. On the other hand, another very important finding is that although 99% of these tumours are ER positive only about 77% of patients receive adjuvant endocrine therapy which is, by itself, a very important finding because it means that these patients are not receiving what is assumed to be one of the best treatments for the disease.
So what has been going wrong in the past then?
I believe it’s mostly because of being a rare disease, of not existing prospective data, that patients are managed a little bit according to the experience of the oncologist. So with this study we hope to provide insights on the biology. It also gives us the possibility of analysing in depth these samples and at the same time we have already launched the second part of the programme which is a prospective registry and we are already developing the third part of the programme which is a randomised trial.
So what insights have you already gained into this disease?
Apart from the clinical part of how the patients have been managed we realised that now that male breast cancer is mostly an ER positive, PR positive and also androgen receptor positive disease. Only about 9% have HER2 positive disease and less than 1% have triple negative disease meaning that if an oncologist receives the pathology report of a male patient and it’s a triple negative or a HER2 positive the first thing to do is to re-discuss with the pathologist and make sure that it’s really indeed the fact.
It sounds as though there are quite a few therapeutic opportunities offered by that characterisation of the tumour then?
Indeed. So one of them certainly can be improved, the administration of adjuvant endocrine therapy, and one of the trials that are being already in late stage of developing is using androgen receptor inhibitor in these patients.
In your study you discovered that in fact over the period of the time covered by the study treatment for male breast cancer has actually improved or outcomes have improved.
The outcomes have improved so the overall survival is substantially improved but that also has to do with the fact that life expectancy in males has improved. The breast cancer specific survival has improved but much less than what we have seen in this last twenty years for the women. On the other hand, some parts of the treatment have improved: over these twenty years more patients are receiving endocrine therapy, more patients are receiving radiation. However, for example, mastectomy rates have not changed over time.
Right. So what are the clinical messages coming out of this? It sounds as if there is potential, what do you advise doctors to be doing?
First of all to be attentive to the biology of the disease, not to forget the importance of adjuvant endocrine therapy in this particular ER positive disease. For the adjuvant setting all the data that we have is for the use of Tamoxifen. It was a bit disturbing to see that a small percentage, but still a substantial percentage, is receiving aromatase inhibitors alone and we actually do not know and the data that we have points for a lower efficacy of these agents. So there are a couple of important messages while we are waiting for randomised data on how to manage these patients.
So if you were to sum up what doctors need to remember from the facts that you’ve discovered in a few words, how would you summarise that?
Discuss with the patient regarding breast conserving surgery; albeit we discuss that with women, we don’t discuss it with men so often. Don’t forget the importance of radiation therapy in these patients that often have node positive disease. And do not forget adjuvant endocrine therapy with Tamoxifen.