I was asked to talk about neoadjuvant chemotherapy in breast cancer simply because last year we had to read and comment on the Early Breast Cancer Collaborative Group’s publication in The Lancet comparing patients who have been entered into primary chemotherapy versus adjuvant chemotherapy trials. The data showed that there is a 5.5% increase in local recurrence out at fifteen years with primary chemotherapy. The data also showed that there was no apparent difference in overall survival but of course the meta-analysis didn’t really have the power to detect a small difference in survival.
What was discussed during the session?
The main issues for us surgeons are that primary chemotherapy really needs to be revisited based on this data. It is now more generally offered and more widely offered, particularly because it is perceived that patients who are triple negative and patients who are node positive should all receive primary chemotherapy at the outset and there is no level 1 evidence supporting that practice. There is evidence, however, that primary chemotherapy should be offered to patients who would like to avoid mastectomy but, of course, in many countries sadly mastectomy is offered because of the surgeon for surgical reasons. So we would have a much greater impact on practice if we were to ensure that patients who are suitable for breast conservation are offered it at the outset.
Nevertheless, there is a swing seen in the EBCTCG data towards breast conservation, a swing of 16%. So there is a 16% benefit in terms of breast conservation observed in the patients who received primary chemotherapy, neoadjuvant chemotherapy.
How can we demonstrate and show that breast conservation is the better way to go?
It all boils down to training and understanding of the published literature to date. The underlying hypothesis, of course, is that given the very eminent surgeon, Bernard Fisher, has stated several decades ago that breast cancer should really be regarded as a systemic disease and that prognosis is predetermined. He was only partially right because a good proportion, roughly two-thirds of patients, are cured really by surgery alone and we need to remind ourselves of that. So primary chemotherapy is a useful tool, it should be used in patients who would like to avoid mastectomy if they are not suitable for breast conservation to start off with because it is able to downsize patients. The other apparent indications for neoadjuvant chemotherapy are not backed by level 1 evidence, sadly.
There is a growing interest, as I mentioned, in using primary chemotherapy in patients who are node positive because it is believed that if you downsize the axilla you can avoid axillary clearance. My concern is that there is no level 1 evidence supporting that premise. Of course, the fact that by doing so in patients with significant disease in the axilla, by implication it means leaving behind nodes that are apparently on imaging they are normal but leaving them behind and leaving them untreated. There is no evidence that you can do that, even in patients who have had a pathological complete response to the axilla. That is really stating the obvious but I think we need to be very careful and we need to be doing clinical trials to evaluate that potential benefit. We need to prove it before we can start generalising it.