Introduction: Promestriene (3-propyl ethyl, 17B-methyl estradiol) is a synthetic estrogen analogue with potential as a topical treatment for vaginal atrophy caused by estrogen deprivation. Topical Promestriene is minimally absorbed with chronic use and has been reported to significantly improve the symptoms of vaginal atrophy. However, to be considered for use for these symptoms in estrogen responsive post-menopausal breast cancer survivors on an aromatase inhibitor, Promestriene would need to show none of the cyto-proliferative properties of estrogen. Methods: We conducted in vitro testing of estrogen responsive breast cancer cell line MCF-7, T-47D, and BT-474 for dose-dependent, estrogen-like functional responses to Promestriene in both estrogen-rich and estrogen-deprived conditions. As assay controls, cultures treated with Fulvestrant, Testosterone, Progesterone and Estradiol were analyzed in parallel. Analysis: Dose dependent Estrogen-like responses in the cell lines were measured as 1) proliferation using flow cytometric analysis of CSFE fluorescence, 2) estrogen receptor expression by flow cytometry, and 3) GREB 1 RNA expression using TaqMan real time PCR quantitative analysis. All cultures were grown to quiescence in RPMI medium supplemented with 10% fetal calf serum. To induce estrogen deprivation, half of the cultures were then held 3 days in media pre-treated and containing anti-estrogen specific antibodies to sequester any residual estrogen from the culture. Data for each culture treatment were analyzed using linear regression analysis and compared using multifactorial or pairwise analyses to determine the significance of estrogen-like responses relative to the estradiol and untreated controls. Results: In estrogen sufficient cultures, Promestriene exhibited no cell proliferative properties on MCF-7, BT-474, or T47-D tumor cells, even at very high concentrations. However, when estrogen in the media was sequestered and culture allowed to quiesce without estrogen receptor stimulation, low dose Promestriene effects on cell proliferation in MCF-7 estrogen responsive cells were not significantly different from low dose estradiol. Low dose Promestriene (2-10pg/ml), unlike comparable doses of estradiol, did not stimulate GREB1 expression in MCF-7 cells. In contrast, T-47D and BT-474 cell lines proliferated and increased GREB- expression in response Promestriene or Fulvestrant treatments. Conclusions: The potential estrogen-like properties of Promestriene to stimulate the growth of estrogen receptor responsive breast cancer cell lines, especially in estrogen-deprived conditions, suggest caution when prescribed for vaginal atrophy in post-menopausal breast cancer survivors on an aromatase inhibitor. Its ability to activate growth and gene expression in ER- breast cancer cells warrants further study. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-07.

Introduction: Hispanic women have lower breast cancer incidence, but a worse five-year survival rate, compared to non-Hispanic white women. As seen in other cancers, this disparity in outcomes may reflect being diagnosed at an advanced stage. Such disparities have been explained by nationwide studies as due to socioeconomic or cultural differences impeding access to quality health care. We reviewed data from the Florida Hospital System (FHS) to discover clinical variables that may influence the survival disparity. Study Population: The eight Central Florida campuses of FHS are major health care providers serving an ethnically diverse population, including 22.9% Hispanics. Over 95% of cases in the Florida Hospital tumor registry are insured patients with one or a combination of Medicaid, Medicare and various types of commercial insurance. With a data set limited to patients with insurance at diagnosis, the FHS patient population provides a uniquely appropriate patient population to differentiate the cause/effect of disparities in clinical outcome of breast cancer from other socioeconomic mitigating factors. Methods: We compared the diagnostic stage, survival and tumor marker tests of Hispanic and non-Hispanic white breast cancer patients diagnosed at the FHS and explored factors that may influence diagnosis, survival and tumor marker tests. Hispanic and non-Hispanic white female patients (≥ 18 yr) who were first diagnosed with a single breast cancer tumor at the FHS between 2001 and 2006 were included. Multiple Logistic regression analyses were used to estimate odds ratios (OR) of late to early stage in relation to ethnicity, age and insurance type. Multiple Cox proportional hazard models and cumulative incidence functions were used to compare death rates between the two ethnicities. Results: A total of 1131 patients were included: 134 identified as Hispanic and 997 as non-Hispanic white. Hispanics were found to be over 10 times as likely as non-Hispanic whites to have Medicaid insurance (OR = 10.15, 95% C.I.: 4.99-20.70). Medicaid patients were more likely to be diagnosed at a late stage than non-Medicaid patients (OR = 4.73; 95% C.I.: 2.16-10.38; p<0.001). As age increased, patients were less likely to be diagnosed at a late stage (OR = 0.86; 95% C.I.: 0.74-0.99; p = 0.038). The death rate was associated with age, insurance type, and stage rather than ethnicity. Hispanic patients had significantly higher percentage of PR positive than non-Hispanic patients (83.1% vs. 72.5%, p = 0.048). No association between ER/HER2 positive and ethnicity was detected. Conclusions: In this study population, there was no significant difference in survival based solely on ethnicity. Our findings support that interventions are needed to enhance the awareness of young people of early screening, and to improve equal access to early screening for people of low socioeconomic status or Medicaid insured patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-12-04.