Our proposed exploratory study focuses on a significant problem: the absence of data on long-term trends in breast cancer tumor profiles, overall and in relation to race/ethnicity and socioeconomic position. The value of such long-term data is that they can uniquely reveal what aspects of tumor biology are amenable to change. Relevant examples include: (1) the long-term rise and recent fall of breast cancer incidence, following sharp decreases of hormone therapy use after publication of the Women's Health Initiative results in 2002, with US declines varying by estrogen receptor (ER) status, socioeconomic position and race/ethnicity, and (2) our new study documenting that between 1992 and 2005, the US white/black odds ratio for ER+ tumors among breast cancer cases likewise rose and fell. These findings, along with new work on the epigenetic regulation of breast tumor evolution and biomarkers, suggest that: (a) the biological expression and social patterning of breast cancer, far from being fixed, can change, and (b) analyzing data on long-term trends has important implications for both understanding the causes of and reducing racial/ethnic and socioeconomic disparities in breast cancer incidence, survival, and mortality. In this R21, we accordingly propose to assess the feasibility of conducting an R01 on long-term trends in breast cancer tumor profiles, overall and by race/ethnicity and socioeconomic position, by determining: (1) if current biomarker assays can be used on tumor specimens extending back to the 1940s, and (2) if, in the selected study population, the proportion of cases for whom we can locate both tumor blocks and medical charts is sufficient for the envisioned R01. The source of the breast tumor specimens will be the United States (US) and New Zealand (NZ), two countries with uniquely long-term cancer registry data and well- documented racial/ethnic and socioeconomic disparities in breast cancer incidence, survival, and mortality.
Our Specific Aims accordingly are:
Aim 1 : Determine the feasibility of locating breast cancer patients' tumor specimens and medical charts, spanning from the 1940s to 2010, from: (a) Kaiser Permanente (KP) Division of Research (Oakland, CA), whose tumor records and patient database extends back to 1947, and (b) The New Zealand Cancer Registry, established in 1948;
Aim 2 : Determine whether current assays for breast cancer biomarkers can validly be employed with specimens dating back to the 1940s, as obtained from Kaiser Permanente (1947-2010);
Aim 3 : Determine if results for Aims 1 and 2 support the feasibility of developing an R01 to study long-term trends in prevalence of - and racial/ethnic and socio- economic disparities in - breast cancer tumor profiles (using the KP and NZ data);
and Aim 4 : Disseminate results by publishing scientific manuscripts and, if warranted, use results to prepare an R01 to conduct the first long-term and cross-country (US and NZ) analysis of trends in breast cancer tumor profiles and racial/ ethnic and socioeconomic disparities in these biomarkers, with major implications for prevention and treatment.
To address a major gap in knowledge regarding long-term trends in breast cancer tumor profiles, overall and in relation to race/ethnicity and socioeconomic position, our proposed exploratory study will assess the feasibility, using data from the United States and New Zealand, of: (1) locating breast cancer patients'tumor specimens and medical charts, dating back to the 1940s up through 2010, and (2) using current biomarker assays on the older as well as more recent tumor specimens, so as to determine (3) if it is feasible to conduct a well-designed and sufficiently large cross-country investigation of long-term trends in breast cancer tumor profiles and racial/ethnic and socioeconomic disparities in these biomarkers. The value of these long- term data is that they can uniquely reveal what aspects of tumor biology are amenable to change. Knowledge produced by the proposed study has the potential to change significantly concepts, methods, and preventive interventions regarding US socioeconomic and racial/ethnic disparities in breast cancer, thereby addressing priorities of both the NIH Office of Behavioral and Social Sciences Research and the Health Disparities Research agenda of the National Cancer Institute's Center to Reduce Cancer Health Disparities.