European Multidisciplinary Cancer Congress (EMCC) 2011, 23-27 September, Stockholm

2011 St Gallen Consensus breast cancer recommendations

Professor Richard Gelber – Dana-Farber Cancer Institute, Boston, USA

Professor Aron Goldhirsch – European Institute of Oncology, Milan

Interviewed by Peter Goodwin.

PG:    Tell me, perhaps Professor Goldhirsch first, about the reason they gave you the award.

AG:    Well the award is given for clinical research within our common activity within the groups, the co-operative groups that we represent. Richard and myself, we are working since 1978, together with the International Breast Cancer Study Group, formally the Ludwig Group, and we conducted several co-operative studies, trials, all over the world with a lot of enthusiasm, many groups and many patients.

PG:    Tell me from your own personal point of view, what’s the thing you’re most enthusiastic about because a lot has happened in breast cancer?

AG:    That allows me to connect to the St Gallen because I think that the most important issue is the recognition of the heterogeneity of breast cancer; the fact that breast cancer is not a single disease but rather a variety of diseases which have to be dealt with in a different way, especially therapeutically.

PG:    Dr Gelber, yes.

RG:    This describes the fact of the importance of the co-operative group networks with which we work. So we started with the International Breast Cancer Study Group but as subtypes meant that smaller and smaller cohorts of breast cancer patients had to be recruited to trials, we needed to expand our reach. So about thirteen years ago, Professor Goldhirsch is very modest about this, as a co-developer of the Breast International Group which brought individual co-operative groups, such as the International Breast Cancer Study Group, together for groups all around the world to build a critical mass of investigators to solve these problems.

PG:    And we’ve been hearing from the BIG here at the meeting, haven’t we?

RG:    Exactly.

PG:    Dr Gelber, your biggest enthusiasm, then, before we move on to the St Gallen recommendations.

RG:    I’m a statistician and I have been impressed for the last 35 years of research in breast cancer that the term breast cancer as a heterogeneous disease is getting more specific during the past decades as we understand markers for defining the heterogeneity. I’m enthusiastic about exploring different treatments for different sub-populations.

PG:    And different treatments, indeed, are emerging, some very exciting ones. The St Gallen consensus meeting in 2011 highlighted the diversity of breast cancer and declared, the publication following the meeting, declared a new approach. Could you perhaps, Professor Goldhirsch, begin by telling me what is this new approach?

AG:    The new approach is rather the recognition of the heterogeneity which means we have enhanced methods which explore the genes of the disease and manage to distinguish between various types and dependence of the genes that are on or off during a specific phase of the life of the tumour.

PG:    And gene arrays, for instance, have been used as a way of testing which ones.

AG:    The gene arrays are the testing of the genes which are off and on. So by doing that you can see some subtypes which, if you look better at the subtypes, you can understand that they are likely to respond to different types of treatments. That allocation of the disease type and the specific treatment that it deserves is actually the news.

PG:    Equally, from my reading of the St Gallen recommendations, clinicopathological factors, criteria, are equally important or perhaps part and parcel of the same thing. Could you throw some light on this please, Richard?

RG:    Yes, in the past we recognised the heterogeneity based on clinicopathological features. With the new evidence from gene arrays, these differences are genetically based. Now the gene arrays are available in some parts of the world more than others, the St Gallen conference is a consensus internationally. So we reached consensus from various parts of the world and what we developed is a shorthand using clinicopathological features to mimic the readout of gene expression arrays so that even in the absence of an array readout, individual clinics, based on clinicopathological features, can organise patient treatment according to subtype.

PG:    Well let’s get down to brass tacks, as we say in the north of my country. What actually was decided in St Gallen? It’s a most august meeting, a most trusted meeting, what about the categories, what about the treatments?

AG:    Well the categories were borrowed, in terms of their name, from the intrinsic subtypes obtained by genetic arrays. The subtypes were the following: so-called luminal A, which correspond to tumours which have a very high concentration of cells which are positive for hormone receptors, both hormone receptors, don’t have the HER2 gene amplified or over-expressed and have a very low proliferation. This type is a typically endocrine responsive type of tumour for which we can allocate some specific treatment.

RG:    Hormone therapies.

AG:    Then you have the other types which are luminal B, both the luminal B containing HER2 and not containing HER2, both are endocrine responsive but not sufficiently endocrine responsive. So there we need to add some specific treatment which is above and beyond the endocrine therapy.

PG:    Well the systemic adjuvant treatments that are available, Dr Gelber, what has come out of St Gallen, then, as prime recommendations?

RG:    Continuing on what Aron suggested, luminal A, sufficient for endocrine therapy treatment, patients do well under that care. Luminal B, higher proliferation requires something else. If HER2 is expressed then treatment such as trastuzumab or other anti-HER2 regimens need to be added in order to get maximum benefit. Patients absent either endocrine responsive disease require chemotherapy to get the best approach for patient care.

AG:    So that category of patients who have tumours with no type of marker of responsiveness, no receptors, no HER2, these patients will require in their treatment a chemotherapy as the backbone.

PG:    What do both of you consider to be the biggest steps forward in adjuvant therapy for early breast cancer as you’ve observed over the past few years and, indeed, believed by the St Gallen meeting?

AG:    Saving the right treatment for the right type, that is the key for a currently modern and proper treatment.

RG:    The first consensuses were generally based on tumour burden which is a marker of the biology underlying the situation. Now we’re getting at the root cause of what the disease is and, more importantly, what the targets are for the available treatments so that we don’t give treatment unnecessarily to patients whose disease doesn’t have the target. That’s specifically endocrine therapy for endocrine responsive; anti-HER2 therapy for HER2 positive; chemotherapy as the backbone for the rest.

PG:    Indeed, chemotherapy is still a backbone.

RG:    Absolutely; for certain patient subtypes, absolutely.

PG:    And the role of anthracyclines?

RG:    There are different types of chemotherapy, Aron can speak much more directly to that, but there are different targets within the cells that respond better or worse to different types of chemotherapy, different regimens, different schedules.

PG:    And I did notice there was a big nod in the recommendations towards reducing the aggressiveness of therapy and avoiding collateral damage wherever possible too.

AG:    It is the issue more about the right toxicity to be delivered rather than the entity of the toxicity. So people are starting now to explore whether there are some specific types of cytotoxics that are more reasonably effective in specific subtypes. For instance, the triple negative type of breast cancer might require alkylating agents among which platinum, which was never recognised as a very effective drug for breast cancer, might have a major role there.

PG:    And there’s a case for omitting axillary dissection, isn’t there, too?

RG:    Yes, that was also touched on in the consensus, the surgical contributors to the panel. The consensus discussed it extensively because the recommendations on eliminating axillary dissection are very specific to the types of patients who were enrolled in the trials that suggested it was safe. And there was a great deal of concern about wholesale elimination of axillary dissection, that might actually be harmful.

PG:    And what’s the recommendation, what’s the latest on radiotherapy?

AG:    The radiotherapy, the standard radiotherapy to the entire breast was defined. The current research on partial breast irradiation is still a research item that needs to give its results in the next future and that the youngest patients with breast cancer need a boost beside the radiation therapy. Those were the features with relation to radiotherapy.

RG:    All emerging from clinical trial data of randomised evidence about the issues.

PG:    So we can use radiation in a more refined way now?

RG:    Yes.

PG:    I’d certainly like to congratulate both of you on getting the award but could you round up by giving us some kind of summary of what you think doctors should be taking home from these St Gallen recommendations? What are the key messages?

AG:    The key message for me, as I said in the beginning, is the fact that breast cancer is a heterogeneous disease and therefore requires a differentiated way of dealing with it in therapeutics for this disease.

RG:    For me the key message is that we keep getting better and better at caring for patients with this disease. One of the key recommendations is, within the context of treatments available, patient preference and the influence of the patient on the discussion, the trade-offs of the various treatments, needs to play a role.

PG:    Richard Gelber, Aron Goldhirsch, thank you very much for joining me here on ecancer.tv and it’s great to get the two of you together.

RG:    Thank you very much.

AG:    Thank you very much.