title: [Immunotherapy opportunities in breast cancer].
abstract: The prognostic value of tumor infiltrating lymphocytes in breast cancer has long been recognized by histopathologists. These observations were reaffirmed by recent immunohistochemistry and gene expression profiling studies that also revealed an association between greater chemotherapy sensitivity and extensive lymphocytic infiltration in early stage breast cancers treated with neoadjuvant chemotherapy. These results suggest that local anti-tumor immune response can at least partially control cancer growth and may mediate the antitumor effects of chemotherapy. However, until recently, there was no direct clinical evidence to demonstrate that enhancing anti-tumor immune response could lead to clinical benefit in breast cancer patients. The recent development of clinically effective immune checkpoint inhibitors made it possible to test the therapeutic impact of augmenting the local anti-tumor immune response. Two Phase I clinical trials using single agent anti-PD-1 (MK-3475, pembrolizumab) and anti-PD-L1 (MPDL3280A, atezolizumab) antibodies demonstrated close to 20% tumor response rates in heavily pretreated, metastatic, triple negative breast cancers. The most remarkable feature of the responses was their long duration. Several patients had disease control close to a year, or longer, which has not previously been seen with chemotherapy regimens in this patient population. A large number of clinical trials are currently underway with these and similar drugs in the neoadjuvant, adjuvant and metastatic settings to define the role of this new treatment modality in breast cancer.
authors.affiliation: Yale Cancer Center, Yale School of Medicine, Breast Medical Oncology, New Haven, USA. lajos.pusztai@yale.edu.
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
authors.affiliation: Sebészeti és Molekuláris Patológiai Osztály, Országos Onkológiai Intézet, Budapest, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ladányi
authors.affiliation: B Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály, Országos Onkológiai Intézet, Budapest, Hungary.
authors.forename: Borbála
authors.initials: B
authors.lastname: Székely
authors.affiliation: Radiológiai és Onkoterápiás Klinika, Semmelweis Egyetem, Budapest, Hungary.
authors.forename: Magdolna
authors.initials: M
authors.lastname: Dank
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor
chemical_list: D061026:Programmed Cell Death 1 Receptor