Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitoxantrone (DHAD), an anthracenedione with antineoplastic properties similar to doxorubicin, was tested for therapeutic efficacy and for immunomodulating action on lymphocyte subsets in 16 metastatic breast cancer patients, 12 of whom had been previously treated with chemotherapy. DHAD was given intravenously at a dose of 14 mg/m2 every 21 days. To evaluate total T lymphocytes (CD3), T helper (CD4), and T suppressor/cytotoxic cells (CD8) and the CD4/CD8 ratio, venous blood samples were drawn before and after the first DHAD cycle. Moreover, in 8/16 patients, B lymphocytes (CD20), T suppressor cells (CD8+/CD57+), T cytotoxic cells (CD8+/CD57-), NK (CD16) and IL-2 receptor-expressing cells (CD25) were also measured at the same time. An objective tumor response was achieved in 5/16 (31%) patients and the response rate was significantly higher in patients pretreated with hormone therapy alone than in those pretreated with chemotherapy. No relation was found between clinical response and changes in the CD4/CD8 ratio. Neither the mean number nor the percentage of CD3, CDA and CD8 cells observed after DHAD were significantly different with respect to those seen before. In contrast, the mean number of T suppressor cells, B lymphocytes and CD25-positive cells was significantly lower after than before DHAD administration, whereas no difference was seen in NK cells. These results confirm in humans the immunomodulating properties of DHAD previously described in experimental conditions. However, the DHAD-induced changes in lymphocyte subsets do not seem to be related to the clinical response in breast cancer.
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PMID:Mitoxantrone as a single agent in pretreated metastatic breast cancer: effects on T lymphocyte subsets and their relation to clinical response. 186 50

Tumor-infiltrating lymphocytes (TILs) convey clinically relevant information for primary breast cancers (PBCs). However, limited data characterizing the immunobiology of metastatic breast cancers (MBCs) are available. Here, we examine TILs in surgically resected MBCs relative to their matched PBCs. Tissue microarrays of PBCs and MBCs were labeled for CD3 (total T cells), CD4 (helper T cells), CD8 (cytotoxic T cells), FoxP3 (regulatory T cells), and CD20 (B cells) to characterize TILs. Expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER-2) classified the tumors as luminal (ER(+)/PR(+)/HER-2(-)), triple negative (ER(-)/PR(-)/HER-2(-)), or HER-2(+) (ER(-)/PR(-)/HER-2(+)). These analyses reveal 5 novel findings. First, MBCs overall contained fewer TILs (mean, 35.1 CD3(+) TILs/high-power field [hpf]) than their matched PBCs (mean, 23.6 CD3(+) TILS/hpf), with fewer CD20(+) cells than CD3(+) cells in PBC and MBC (P = .0247). Second, the number of CD3(+), CD8(+), CD4(+), and FoxP3 TILs was decreased in triple-negative MBCs relative to matched PBCs, whereas only CD8(+) TILs were decreased in luminal MBCs relative to matched PBCs. Third, triple-negative MBCs contain fewer TILS (mean, 16 CD3(+) TILs/hpf) than luminal MBCs (mean, 21.7 CD3(+) TILs/hpf). Fourth, brain metastases contained fewer TILs relative to MBC from other sites. Finally, in this series, a CD8(+)/FoxP3(+) T-cell ratio of 3 or greater in PBCs was associated with improved overall survival from diagnosis, whereas a CD8(+)/FoxP3(+) T-cell ratio less than 3 in MBCs at first relapse was associated with improved overall survival. These findings suggest that evaluating the immunologic microenvironment of both PBCs and MBCs may yield important clinical information to guide breast cancer prognosis and therapy.
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PMID:Metastatic triple-negative breast cancers at first relapse have fewer tumor-infiltrating lymphocytes than their matched primary breast tumors: a pilot study. 2370 42

Bone metastases are prevalent in many common cancers such as breast, prostate, and lung cancers, and novel therapies for treating bone metastases are needed. Human immune system-engrafted models are used in immuno-oncology (IO) studies for subcutaneous cancer cell or patient-derived xenograft implantations that mimic primary tumor growth. Novel efficacy models for IO compounds on bone metastases need to be established. The study was performed using CIEA NOG (NOG) mice engrafted with human CD34+ hematopoietic stem cells (huNOG) and age-matched immunodeficient NOG mice. Bone phenotyping was performed to evaluate baseline differences. BT-474 human breast cancer cells were inoculated into the tibia bone marrow, and cancer-induced bone changes were monitored by X-ray imaging. Bone content and volume were analyzed by dual X-ray absorptiometry and microcomputed tomography. Tumor-infiltrating lymphocytes (TILs) and the expression of immune checkpoint markers were analyzed by immunohistochemistry. Bone phenotyping showed no differences in bone architecture or volume of the healthy bones in huNOG and NOG mice, but the bone marrow fat was absent in huNOG mice. Fibrotic areas were observed in the bone marrow of some huNOG mice. BT-474 tumors induced osteoblastic bone growth. Bone lesions appeared earlier and were larger, and bone mineral density was higher in huNOG mice. huNOG mice had a high number of human CD3-, CD4-, and CD8-positive T cells and CD20-positive B cells in immune-related organs. A low number of TILs and PD-1-positive cells and low PD-L1 expression were observed in the BT-474 tumors at the endpoint. This study reports characterization of the first breast cancer bone growth model in huNOG mice. BT-474 tumors represent a "cold" tumor with a low number of TILs. This model can be used for evaluating the efficacy of combination treatments of IO therapies with immune-stimulatory compounds or therapeutic approaches on bone metastatic breast cancer.
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PMID:Human Immune System Increases Breast Cancer-Induced Osteoblastic Bone Growth in a Humanized Mouse Model without Affecting Normal Bone. 3121 Nov 47

Immune cells are present in normal breast tissue and in breast carcinoma. The nature and distribution of the immune cell subtypes in these tissues are reviewed to promote a better understanding of their important role in breast cancer prevention and treatment. We conducted a review of the literature to define the type, location, distribution, and role of immune cells in normal breast tissue and in in situ and invasive breast cancer. Immune cells in normal breast tissue are located predominantly within the epithelial component in breast ductal lobules. Immune cell subtypes representing innate immunity (NK, CD68+, and CD11c+ cells) and adaptive immunity (most commonly CD8+, but CD4+ and CD20+ as well) are present; CD8+ cells are the most common subtype and are primarily effector memory cells. Immune cells may recognize neoantigens and endogenous and exogenous ligands and may serve in chronic inflammation and immunosurveillance. Progression to breast cancer is characterized by increased immune cell infiltrates in tumor parenchyma and stroma, including CD4+ and CD8+ granzyme B+ cytotoxic T cells, B cells, macrophages and dendritic cells. Tumor-infiltrating lymphocytes in breast cancer may serve as prognostic indicators for response to chemotherapy and for survival. Experimental strategies of adoptive transfer of breast tumor-infiltrating lymphocyte may allow regression of metastatic breast cancer and encourage development of innovative T-cell strategies for the immunotherapy of breast cancer. In conclusion, immune cells in breast tissues play an important role throughout breast carcinogenesis. An understanding of these roles has important implications for the prevention and the treatment of breast cancer.
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PMID:The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer. 3289 93