Resistin: An inflammatory cytokine with multi-faceted roles in cancer.

Systemic and organ-confined inflammation has been associated with cancer development and progression. Resistin, initially described as an adipocyte-derived cytokine in mice, is mostly expressed by the macrophages in humans. It has potent pro-inflammatory properties, and its elevated serum levels are detected in cancer patients. Aberrant expression of resistin receptors is also reported in several malignancies and associated with aggressive clinicopathological features. Several lines of evidence demonstrate that resistin, acting through its different receptors, promotes tumor growth, metastasis, and chemoresistance by influencing a variety of cellular phenotypes as well as by modulating the tumor microenvironment. Racially disparate expression of resistin has also attracted much interest, considering prevalent cancer health disparities. This review discusses the aberrant expression of resistin and its receptors, its diverse downstream signaling and impact on tumor growth, metastasis, angiogenesis, and therapy resistance to support its clinical exploitation in biomarker and therapeutic development.

Inflammation, immunosuppressive microenvironment and breast cancer: opportunities for cancer prevention and therapy.

Breast cancer is the most commonly diagnosed malignancy and a leading cause of cancer-related death in women worldwide. It also exhibits pronounced racial disparities in terms of incidence and clinical outcomes. There has been a growing interest in research community to better understand the role of the microenvironment in cancer. Several lines of evidence have highlighted the significance of chronic inflammation at the local and/or systemic level in breast tumor pathobiology. Inflammation can influence breast cancer progression, metastasis and therapeutic outcome by establishing a tumor supportive immune microenvironment. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation. Targeting of immune and inflammatory pathways has met tremendous success in some cancers underscoring the importance of research to further our understanding of these systems in breast cancer. This knowledge can be helpful not only in the development of novel prevention and therapeutic strategies, but also help in better prediction of therapeutic responses in patients. This review summarizes some of the significant findings on the role of inflammation in breast cancer to gain collective molecular and mechanistic insights. We also discuss ongoing efforts and future outlook to exploit the existing knowledge for improved breast cancer management.

Patient and Tumor Disparities in Breast Cancer Based on Insurance Status.

This study seeks to determine whether uninsured breast cancer patients are more likely to present with advanced disease relative to insured patients. We retrospectively reviewed newly diagnosed breast cancer patients over a 27-month period. Patients were sorted based on insurance status at diagnosis. Demographic and tumor-specific data were collected and analyzed using nonparametric testing. We identified 276 breast tumors in 260 patients. Out of the 260 patients, 71 patients (27.3%) were uninsured and were more likely to be black (P < 0.05), present with a breast-specific complaint rather than an abnormal mammogram (P < 0.05), and present with more advanced disease (52% stage II or worse vs 26.6% in the insured population; P < 0.01). Percentage of invasive carcinoma and tumor biology were independent of insurance status. Insured patients were more likely to receive surgery as first therapy (76.5 vs 46.0%, P < 0.01), whereas uninsured patients were more likely to receive chemotherapy suggesting multimodality treatment. Uninsured patients had a longer time to therapy initiation (56.0 days vs 44.5 days, P < 0.05). Our study confirms that uninsured patients present with higher stage disease are more likely to have breast-specific complaints and are more likely to require chemotherapy as first-line treatment confirming the under-utility of screening mammography within our uninsured patients.

Current operative management of breast cancer: an age of smaller resections and bigger cures.

Surgical resection was the first effective treatment for breast cancer and remains the most important treatment modality for curative intent. Refinements in operative techniques along with the use of adjuvant radiotherapy and advanced chemotherapeutic agents have facilitated increasingly focused breast cancer operations. Surgical management of breast cancer has shifted from extensive and highly morbid procedures, to the modern concept obtaining the best possible cosmetic result in tandem with the appropriate oncological resection. An ever-growing comprehension of breast cancer biology has led to substantial advances in molecular diagnosis and targeted therapies. An emerging frontier involves the breast cancer microenvironment, as a thorough understanding, while currently lacking, represents a critical opportunity for diagnosis and treatment. Collectively, these improvements will continue to push all therapeutic interventions, including operative, toward the goal of becoming more focused, targeted, and less morbid.

Matrix-producing carcinoma: a rare variant of metaplastic breast carcinoma with heterologous elements.

Matrix-producing carcinoma (MPC) of the breast is a rare variant of the uncommon group of malignancies categorized as metaplastic breast carcinomas with heterologous elements. The major criterion for a diagnosis of MPC is the presence of invasive breast carcinoma with the direct transition to a cartilaginous or osseous stromal matrix without an intervening spindle cell component. The cellular origin of MPC remains unclear. It has been suggested that tumor cells in MPC have combined epithelial and mesenchymal features. Several reports have suggested that the tumor cells originate from myoepithelial cells. The prognosis of patients with MPC was originally described as similar to invasive mammary carcinomas of no special type (NST) of the same stage, but a more recent study has shown a worse prognosis than same-stage NSTs.

Epigenetic silencing contributes to the loss of BRMS1 expression in breast cancer.

Breast Cancer Metastasis Suppressor 1 (BRMS1) suppresses metastasis of human breast cancer, ovarian cancer and melanoma in athymic mice. Studies have also shown that BRMS1 is significantly downregulated in some breast tumors, especially in metastatic disease. However, the mechanisms which regulate BRMS1 expression are currently unknown. Upon examination of the BRMS1 promoter region by methylation specific PCR (MSP) analysis, we discovered a CpG island (-3477 to -2214), which was found to be hypermethylated across breast cancer cell lines. A panel of 20 patient samples analyzed showed that 45% of the primary tumors and 60% of the matched lymph node metastases, displayed hypermethylation of BRMS1 promoter. Furthermore, we found a direct correlation between the methylation status of the BRMS1 promoter in the DNA isolated from tissues, with the loss of BRMS1 expression assessed by immunohistochemistry. There are several studies investigating the mechanism by which BRMS1 suppresses metastasis; however thus far there is no study that reports the cause(s) of loss of BRMS1 expression in aggressive breast cancer. Here we report for the first time that BRMS1 is a novel target of epigenetic silencing; and aberrant methylation in the BRMS1 promoter may serve as a cause of loss of its expression.

Metaplastic breast carcinoma with osseous differentiation: a case report.

Metaplastic breast carcinoma is a rare entity with the distinguishing feature of having epithelial and mesenchymal tissue types incorporated within one tumor. This is a case report of a patient found to have a rare metaplastic breast carcinoma with prominent osseous differentiation. Radiologic and pathologic correlation is provided.

Fibromatosis: the breast cancer imitator.

Fibromatosis of the breast is a rare benign tumor that should be included in the differential diagnosis for breast cancer. It is usually indistinguishable from malignancy on ultrasound, mammography, physical examination, and on gross evaluation. Distinction is easily made by histologic findings. This benign tumor does not metastasize, but is locally aggressive and tends to recur postoperatively, which accounts for considerable morbidity. We present two cases and a discussion from the perspective of the radiologist, the surgeon, and the pathologist.

Infiltrating syringomatous adenoma of the nipple: a case report and 20-year retrospective review.

Infiltrating syringomatous adenomas are rare lesions of the nipple that were first described in 1983. The exact origin of these lesions is uncertain, although derivation from eccrine structures of the nipple has been postulated because the lesions are microscopically reminiscent of other tumors of eccrine origin, such as syringomatous carcinoma. The lesions are usually infiltrative, showing an expansile pattern of proliferation into adjacent tissues of the nipple and underlying breast. Involvement of the epidermis, however, has not been described. The lesions behave in a benign fashion, with no evidence of regional or distant metastasis in any of the reported cases. Complete local excision appears to be sufficient therapy, with only incompletely excised cases showing recurrence. We report an additional case of infiltrating syringomatous adenoma of the nipple and review the medical literature related to this lesion published in the 20 years since its initial description.