2011 SABCS, San Antonio Breast Cancer Symposium, 6-10 December, San Antonio, USA

Genetic differences responsible for outcome in hormone receptor positive early stage breast cancer

Professor Minetta Liu – Georgetown University, Washington, USA

Our primary interest was in trying to understand, in hormone receptor positive early stage breast cancer, why some people, some women with breast cancer developed recurrences very early in their treatment course though some develop it much later in their disease course and, in fact, some never do. If we could, at the time of diagnosis, understand why and predict what would happen to those women, maybe we could actually do something about it to make those potential recurrences never recurrences.

We began by looking at baseline biopsies obtained from women who were newly diagnosed with early stage hormone receptor positive breast cancer and first of all identified that there are clear genetic patterns in those women that have breast cancers that recur early versus late versus never. We really focussed on the early versus late distinction. More importantly, we went beyond trying to predict if someone would recur early or late by actually looking at the molecular differences between these two patient populations to see if we can figure out how we can, again, affect the underlying biology of these tumours.

So this is very early in our work but we’ve identified clear differences: number one and number two, we’ve identified important genes that look like they play a role in these recurrences so we hope to manipulate them.

What differences were found?

In the early recurrence population, for example, we saw Src, map kinases genes that came up; in late recurrences we saw EGFR, the epidermal growth factor receptor, the oestrogen receptor and, interestingly enough, the androgen receptor as well. And these are druggable targets, we have agents that affect most of these already so we hope to bring those agents earlier in treatment and try to investigate whether or not we can actually make a difference.

So we need to validate this further, we need to, importantly, look at those women with tumours that never recur because that’s really the goal. So if we can identify that biology and see if we can again manipulate the other tumours to act more like that and we’re going to start certainly with rat models. To do this in animals but in parallel conduct some clinical trials again because there are already agents out there that we can combine with endocrine therapy, again to see if we can do better.

So, as a standard of care we use tamoxifen or aromatase inhibitors depending on the patient and the situation. The question would be can we use these drugs that are already out there in other clinical trials and be intelligent about how we combine them and how we study them in the patient population that we use to, again, make steps forward a little bit faster.