Culturally Tailored Cancer Communication, Education, and Research: The Highways and Back Roads of Appalachia

We have varying experiences with Appalachia, yet we all agree that there is a unique relationship between Appalachians and cancer. Two of us are nurses who have worked with various communities. Two of us grew up here; 1 watched several of her relatives battle cancer in their Appalachian homes. All of us are scholars who want to talk with practitioners and researchers who are developing culturally tailored cancer control interventions. This goal to have a dialogue emerged after we had a series of discussions about cancer in Appalachia, discussions resulting in our developing a list of cultural traits that seem to be related to this region’s high cancer morbidity and morality (Table). For example, in one of our previous publications we describe the association between the traditional Appalachian oral culture and the cancer experience, finding that cancer stories appeared to pass from 1 generation to the next (1). In turn, these stories seem to affect some community members\u27 willingness to be screened. Our essay\u27s purpose is not to justify the elements presented in the Table. Rather, we write to consider the following: What are the advantages and disadvantages of making generalizations about a culture that has already been marginalized by overgeneralizations

Towards an integrated model for breast cancer etiology: The lifelong interplay of genes, lifestyle, and hormones

While the association of a number of risk factors, such as family history and reproductive patterns, with breast cancer has been well established for many years, work in the past 10–15 years also has added substantially to our understanding of disease etiology. Contributions of particular note include the delineation of the role of endogenous and exogenous estrogens to breast cancer risk, and the discovery and quantification of risk associated with several gene mutations (e.g. BRCA1). Although it is difficult to integrate all epidemiologic data into a single biologic model, it is clear that several important components or pathways exist. Early life events probably determine both the number of susceptible breast cells at risk and whether mutations occur in these cells. High endogenous estrogens are well established as an important cause of breast cancer, and many known risk factors appear to operate through this pathway. Estrogens (and probably other growth factors) appear to accelerate the development of breast cancer at many points along the progression from early mutation to tumor metastasis, and appear to be influential at many points in a woman's life. These data now provide a basis for a number of strategies that can reduce risk of breast cancer, although some strategies represent complex decision-making. Together, the modification of nutritional and lifestyle risk factors and the judicious use of chemopreventive agents could have a major impact on breast cancer incidence. Further research is needed in many areas, but a few specific arenas are given particular mention

Association of Estrogen Metabolism with Breast Cancer Risk in Different Cohorts of Postmenopausal Women

Endogenous estradiol and estrone are linked causally to increased risks of breast cancer. In this study, we evaluated multiple competing hypotheses for how metabolism of these parent estrogens may influence risk. Prediagnostic concentrations of estradiol, estrone, and 13 metabolites were measured in 1,298 postmenopausal cases of breast cancer and 1,524 matched controls in four separate patient cohorts. The median time between sample collection and diagnosis was 4.4 to 12.7 years across the cohorts. Estrogen analytes were measured in serum or urine by liquid chromatography-tandem mass spectrometry. Total estrogen levels (summing all 15 estrogens/estrogen metabolites) were associated strongly and positively with breast cancer risk. Normalizing total estrogen levels, we also found that a relative increase in levels of 2-hydroxylation pathway metabolites, or in the ratio of 2-hydroxylation:16-hydroxylation pathway metabolites, were associated inversely with breast cancer risk. These associations varied by total estrogen levels, with the largest risk reductions occurring in women in the highest tertile. With appropriate validation, these findings suggest opportunities for breast cancer prevention by modifying individual estrogen metabolism profiles through either lifestyle alterations or chemopreventive strategies. Cancer Res; 77(4); 918-25. ©2017 AACR

Association of Estrogen Metabolism with Breast Cancer Risk in Different Cohorts of Postmenopausal Women

Endogenous estradiol and estrone are linked causally to increased risks of breast cancer. In this study, we evaluated multiple competing hypotheses for how metabolism of these parent estrogens may influence risk. Prediagnostic concentrations of estradiol, estrone, and 13 metabolites were measured in 1298 postmenopausal cases of breast cancer and 1524 matched controls in four separate patient cohorts. Median time between sample collection and diagnosis was 4.4–12.7 years across the cohorts. Estrogen analytes were measured in serum or urine by liquid chromatographic-tandem mass spectrometry. Total estrogen levels (summing all 15 estrogens/estrogen metabolites) were associated strongly and positively with breast cancer risk. Normalizing total estrogen levels, we also found that a relative increase in levels of 2-hydroxylation pathway metabolites, or in the ratio of 2-hydroxylation:16-hydroxylation pathway metabolites, were associated inversely with breast cancer risk. These associations varied by total estrogen levels, with the largest risk reductions occurring in women in the highest tertile. With appropriate validation, these findings suggest opportunities for breast cancer prevention by modifying individual estrogen metabolism profiles through either lifestyle alterations or chemopreventive strategies