Abstract
Inflammatory cells are emerging markers in various cancers in human trials. The relationship between the inflammatory cells response, cancer grade, and progression has been investigated experimentally in a spontaneous canine model of breast cancer and in the unselected population (18–64 years.o.) under anti-HER2 treatments that represent the most prevalent population in this cancer type. The canine data (N samples = 101) were collected retrospectively for diagnosis in our regional area and evaluated by immunohistochemistry and haemato-chemistry. The inflammatory and immune-related adverse reactions (ADR) in humans were evaluated using EudraVigilance. The “Proportional Reporting Ratio” (PRR) of the mabs was calculated for each ADR with values >2 indicative of high risk. In dogs, we found elevated immunostaining of CD68-macrophages in the lymph node of the aggressive cancer G3 and infiltrating CD20+-lymphocyte. A high density of CD20 + lymphocytes was observed in G1 and a decrease in the density was observed with the histological degree of the tumors. The animals with the sample in G1 showed reduced serum platelet and neutrophil count and elevated lymphocytes and the opposite in severely affected animals. Inflammatory reactions with edema, skin reactions, extravasation, loss of effectiveness, and platelet count decrease (PRR > 13) were found with trastuzumab emtansine in humans, in the absence of immune system reactions. Trastuzumab i.v.-s.c. showed immune system reactions, loss of effectiveness, intolerances with drug withdrawal, technological issues (PRR > 7), and neutrophil count decrease reports. These reactions were less frequently reported for pertuzumab i.v. Case reports of platelet and neutrophil count decrease were not associated with disease progression with a better outcome in humans as in canine breast cancer. Therefore, infiltrating CD68-macrophages are associated with G3, while infiltrating CD20+ and elevated serum lymphocytes in parallel with reduced platelet and neutrophil count play a favorable role in human and canine breast cancer.
Highlights
Cancer is the second leading cause of death after cardiovascular disease
Case reports showed the first case of trastuzumab emtansine-associated pleural and pericardial effusions in a patient with breast cancer in the absence of other etiologies was reported that was associated with severe inflammatory reactions due to trastuzumab emtansine (Lombardi et al, 2021)
We investigated the relationship between the inflammatory cells response, cancer grade, and progression in the canine breast cancer biopsies collected in our regional area for diagnostic purposes and in the unselected population (18–64 years.o.) under anti-HER2 treatments
Summary
Cancer is the second leading cause of death after cardiovascular disease. Considering the entire population, and taking care of non-melanoma skin cancers, the most frequent tumors are those of the udder and rectum, followed by that of the lung and prostate and in the case of skin cancers, the five most frequently diagnosed cancers among men are prostate cancer, lung cancer, colorectal cancer, bladder cancer, kidney cancer, and urinary tract cancer; among women, breast cancer, colorectal cancer, lung cancer, thyroid cancer, and cervical cancer. Immunotherapy has been developed that uses the patient’s immune system, or certain components stimulating the body’s immune system made it more effective in recognizing and destroying cancer cells. This strategy is based on the fact that inflammatory and immune cells play a role in different cancers. Inflammatory responses with the involvement of the cell infiltrates can be expected in human breast cancer patients under treatment with anti-HER2 monoclonal antibodies (mabs) combined with chemotherapy. A higher rate of peripheral neuropathy and liver disfunction was reported following trastuzumab emtansine treatments in the patients that were associated with inflammatory reactions (Battisti et al, 2020)
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