While several inflammatory cell types participate in cancer development, macrophages specifically play a key role in breast cancer, where they appear to be part of the pathogenesis of high-grade tumors. Tumor-associated macrophages (TAMs) produce factors that promote angiogenesis, remodel tissue and dampen the immune response to tumors. Specific macrophage types contribute to increased metastases in animal models, while human studies show an association between TAMs and tumors with poor prognostic features. Macrophages display a spectrum of phenotypic states, with the tumor microenvironment skewing TAMs towards a 'nonclassical' activation state, known as the M2, or wound healing/regulatory state. These TAMs are found in high-risk breast cancers, making them an important therapeutic target to explore. Improved techniques for identifying TAMs should translate into clinical applications for prognosis and treatment.
African American and Hispanic women develop more triple negative breast cancer at younger ages than Caucasian women. The frequently observed association between race and socioeconomic status (SES) has confounded our understanding of the outcomes disparities seen in these groups. Given the association between inflammatory cells and high-grade, triple negative tumors, we sought to investigate whether differences in the presence of these cells varies by race. We evaluated breast tumor specimens for the presence PCNA+ tumor-associated macrophages (TAMs) in consecutive cases from a county hospital serving primarily un- or under-insured patients. All patients in this cohort had elevated PCNA + TAM levels. Higher PCNA + TAM counts were associated with hormone receptor (HR) negative tumors and non-Caucasian ethnicity. Hispanic women specifically had significantly higher PCNA + TAM counts than Caucasian patients and shorter disease-free survival. These findings implicate immune function in the development of aggressive breast cancer and suggest a possible link between SES and the inflammatory response.
Our findings indicate that breast cancers in Nigerian women have a highly aggressive phenotype (high grade, hormone receptor negative), which is similar to other studies from Africa and other developing nations, as well as from African American women, but is significantly different from Caucasian women in the developed world. The presence of high numbers of TAMs in these tumors raises the possibility of targeting the immune microenvironment for therapeutic interventions.
Objectives To compare utilities for prenatal testing outcomes among women inclined to continue their pregnancy despite abnormal results versus those inclined to terminate and to analyze how differences affect optimal prenatal testing strategies.Method Time tradeoff utilities for 23 outcomes were elicited from 281 women. We compared utilities based on termination inclination and applied them to a decision-analytic framework.Results Of participants, 46.6% indicated that they would 'definitely' or 'probably' continue their pregnancy despite results indicating an intellectual disability. These women assigned higher utilities to abnormal testing results and having a child with an intellectual disability than women who would probably or definitely terminate. Primary cellfree DNA screening had the most quality-adjusted life years for women inclined to continue their pregnancy but yielded an incremental cost-effectiveness ratio (ICER) of $1 685 449. Multiple marker screening with either cell-free DNA or diagnostic testing as follow-up had an ICER of $9037. Primary diagnostic testing resulted in the most quality-adjusted life years for women inclined to terminate, with an ICER of $111 776.Conclusion Women seeking testing vary in prenatal testing outcome preferences and termination inclinations in the context of results indicating an intellectual disability. How they envision utilizing prenatal testing information impacts their optimal testing strategy.
The presence of high numbers of PCNA(+) TAMs and Mac387-positive cells in breast cancers with poor outcomes may implicate a subset of TAMs in breast cancer pathogenesis, and may ultimately serve to develop potential cellular targets for therapeutic interventions.
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