The way forward in breast cancer

The topic of neoadjuvant treatment for breast cancer, and clinical scenarios in which combination therapy is appropriate, was discussed at the Gathering Around Cancer Conference by Dr Ruth O’Regan, University of Rochester Medical Centre, New York, US.

Dr O’Regan also presented trial data and case studies evaluating residual cancer burden following neoadjuvant chemotherapy, although she pointed out this can be subtype-specific.

She synopsised different subtypes of breast cancer and efforts to increase pathological complete response (pCR) rates. In triple-negative breast cancer, around one-third of patients show pCR: “…. In the cohort with pCR, there are still patients relapsing,” said Dr O’Regan.

Dr O’Regan showed data from trials that attempt to address this problem with the use of combination therapies.

The addition of immunotherapy is another welcome treatment advance and she said there is emerging evidence to show stromal tumour-infiltrating lymphocytes (TILs) are prognostic. “If you have very high levels of stromal TILs in the cancer, patients do incredibly well,” she said. “Keep in mind that ‘triple-negative’ is an umbrella term with at least four different subtypes.” She described the standard approaches for drug therapy in each subtype and said: “We know there is significant crosstalk between the oestrogen receptor and HER2 pathways. If you have HER2-positive cancer that starts signalling, it releases co-activators from the oestrogen receptor, blocking ER-regulated gene transcription. Conversely, if you block HER2 on its own, the co-activator remains associated with the oestrogen receptor, and then ER-regulated gene transcription continues, acting as an escape mechanism…. “For ER-negative breast cancer, we are all very comfortable with neoadjuvant therapy and pCR is highly prognostic of outcomes in those patients,” Dr O’Regan concluded. “For ER-positive cancer, it is quite challenging, especially if they are low-grade. It makes sense to give endocrine therapy, but the problem is that you have to give it for so long, and that can pose a problem…. Escalating and de-escalating is the way forward.”