Neo-adjuvant therapy in breast cancer

Neo-adjuvant chemotherapy is a widely accepted practice for patients with large operable or locally advanced tumours. Its main advantage lies in shrinking the primary tumour, reducing the amount of tissue to be removed at surgery. For some women, this turns an inoperable tumour (i.e. a large or locally advanced cancer) into an operable one, improving her chances of a better outcome.
Neo-adjuvant therapy may also reduce the need of a mastectomy to remove a tumour given the relative size of the cancer and her breast to that of a lumpectomy if the tumour is shrunk with neo-adjuvant therapy. Of course, the size threshold for needing a mastectomy depends on breast size, as well as the position of the cancer within the breast. Even in the case of lumpectomies, less tissue may need to be removed if the tumour is shrunk first. This leads to a better cosmetic effect. However, the one limiting factor is that neo-adjuvant therapy is not good at getting rid of ductal carcinoma in situ (DCIS), so that some women may still need a mastectomy due to the extent of the DCIS rather than the size of the primary tumour.
For women who present young with a BRCA1/2 mutation, and therefore favour a double, prophylactic mastectomy if they were gene positive, the advantage of having neo-adjuvant therapy first lies in delaying the surgery to give time for testing, if the test result would alter the surgery required (some women who are shown not to be BRCA1/2 positive may still choose to have a double mastectomy, but others would not).
We most often think of neo-adjuvant therapy as meaning drugs, but there are times (particularly for locally advanced) where giving radiotherapy before rather than the conventional after surgery can facilitate that surgery.
In terms of overall survival, no evidence shows that the chances of surviving breast cancer are influenced by the order of therapy, i.e. the same treatment given before or after surgery seems to have the same long-term outcomes.
Research-wise, the neo-adjuvant setting is a great way to measure what drugs do to a cancer - both in terms of how well they shrink it, but also biologically. The I-SPY programmes in the USA are part of this approach, using the neo-adjuvant technique to better understand new drugs. Some think that changing therapy because the first treatment does not work during neo-adjuvant could be better for the patient, although no hard data exists to support this idea.
As to the choice of therapy - if chemotherapy is going to be given anyway, it is best to use chemo as it tends to cause tumours to shrink faster. If herceptin is being considered, then it is good to add it to the appropriate part of the chemo. This is increasingly a standard of care even if not clearly approved by EMEA! However, hormone therapy is much less toxic for post-menopausal women, especially for those with a lower grade cancer. It is often as effective in terms of tumour shrinkage also, but takes longer - patients probably need up to nine months of therapy before maximal shrinkage. The pathological complete response rate is lower to hormones, but that should not be too discouraging - patients needs five years of adjuvant therapy to get maximal benefit, so it is not surprising that one sixth of treatment does not eradicate as many cancers as all the chemotherapy does!
You may agree or disagree with such opinions. As all this and a lot more will be discussed as part of the Clinical Science Symposia, I urge you to come to the Neo-adjuvant Therapy in Breast Cancer Session on Wednesday 21 March (16.00 to 17.30), and have your say.


**ECCO Communications