12IN - Modulation of immune response in breast cancer and clinical implications

Date 29 September 2014
Event ESMO 2014
Session Cancer immunotherapy in breast cancer: Dream or reality?
Topics Breast Cancer, Metastatic
Cancer Immunology and Immunotherapy
Presenter Sherene Loi
Citation Annals of Oncology (2014) 25 (suppl_4): iv6-iv7. 10.1093/annonc/mdu292
Authors S. Loi
  • Division Of Cancer Medicine, Peter MacCallum Cancer Centre, 3002 - Melbourne/AU

Abstract

Body

Abstract:

Recently, the emergence of effective immunotherapies has become a reality for cancer patients. Immunity has two seemingly paradoxical effects on cancer. On the one hand, immunity prevents against the development of potential tumours, a concept is known as immunosurveillance. On the other hand, immunity can shape the nature of developing tumour through immunological pressure, by selecting out the non-immunological variants. This combination is termed “cancer immunoediting” and describes the ability of some tumours to grow whilst actively avoiding destruction by the immune system. Recent newly-developed therapies that serve to release tumour-mediated immunosuppression, through inhibition of T effector cell negative regulators such as cytotoxic T-lymphocyte antigen-4 (CTLA4) and programmed death 1 (PD-1), have been reported to be effective in metastatic melanoma and lung cancer. Whilst immunotherapies have been traditionally for solid tumour types considered “immunogenic” such as melanoma and renal cell carcinoma, our evidence suggests that certain subtypes of breast cancer may also be amendable to immune approaches. In the triple negative (TNBC) and HER2-overexpressing (HER2+) subtypes, immune surrogates have been correlated with prognosis now in a number of large clinical trial datasets. As clinical trials have carefully collected prospective data on survival, correlations between biomarkers and outcome are considered more robust using these samples. In particular, there is a strong correlation between lymphocytic infiltration and a good outcome in TNBC. In HER2+ disease, innate and adaptive immune responses seem to be important for mediating responses to anti-HER2 therapy. Oncogenic signalling seems to have a role in potentiating immunosuppression in tumours. At present it is unknown if inhibition of T effector cell negative regulators such as anti- CTLA4 and anti-PD 1 will be effective in the treatment of TNBC and HER2+ disease. These phase II trials are about to start. If these compounds are shown to be effective, a new paradigm in the treatment of breast cancer will begin.

Disclosure:

The author has declared no conflicts of interest.