In contrast to the treatment of melanoma or lung cancer, for instance, immunotherapy in the form of checkpoint inhibitors does not yet form part of the standard toolkit in the treatment of breast cancer. This has a number of causes, explains Marleen Kok. "To start with, breast cancer is a disease with a relatively favourable prognosis for which many effective forms of treatment already exist. This makes the need for research into new treatments, including immunotherapy, less urgent than it originally was for metastatic melanoma or lung cancer. But at least as significant is the fact that breast tumours form a less straightforward target for checkpoint inhibitors than do melanomas and lung tumours. After all, these inhibitors work by strengthening the body's existing immune response against the tumour, and this is exactly what may be absent in many breast tumour cases. In the absence of a strong endogenous immune response to the tumour, there isn't much for checkpoint inhibitors to do. What isn't there, can't be strengthened."
This does not, however, imply that the use of checkpoint inhibitors could never be successful in the treatment of breast cancer. "In the studies that have been carried out into the use of checkpoint inhibitors for breast cancer, a small percentage of the patients did, in fact, show a long-term response," Kok notes. "For triple negative breast tumours in particular, clinically relevant results were obtained in the first-line use of checkpoint inhibitors." It is not so strange that it was the triple negative breast tumours that responded comparatively well to checkpoint inhibitors: "Triple negative breast tumours generally contain relatively large numbers of tumour-specific cytotoxic lymphocytes, so-called TILs," Professor Christine Desmedt (KU Leuven, Belgium) explained in an earlier lecture at the 17th Bossche Mamma Congress. "And the presence of TILs in the tumour is a good indicator of success in treatment using checkpoint inhibitors."
For instance, in the KEYNOTE-173 study, in which women with triple negative breast cancer were given neoadjuvant treatment with the checkpoint inhibitor pembrolizumab (plus chemotherapy or placebo), the degree of pathologically complete response (pCR) to the neoadjuvant treatment was correlated with the number of TILs in the tumour. "The tumours of patients showing a pCR contained a relatively large number of TILs, both at the start of neoadjuvant treatment, but particularly during this treatment." Desmedt showed that in the metastatic setting, too, a clear correlation existed between the number of TILs and survival rates during/after treatment with a checkpoint inhibitor.