Wolfson, Emily A

ABSTRACT Background Guidelines recommend primary care practitioners (“PCPs”) engage women ≥ 75 years in shared decision‐making (SDM) around mammography screening. Therefore, we aimed to develop a web‐based conversation aid about mammography screening for women ≥ 75 using output from established simulation models to provide screening outcomes based on > 23,000 combinations of individual women's health and breast cancer risk factors. Methods We used an end‐user centered design approach to develop a prototype web‐based conversation aid incorporating feedback. From July 2023 to April 2024, 10 PCPs from a Boston‐area health system and a safety‐net hospital used the prototype aid during encounters with women ≥ 75 without breast cancer or dementia ( n = 30; 1–5 patients per PCP). We observed aid use and assessed clinician effort to involve patients in SDM using OPTION5 (assesses five components of SDM, scores range 0–100). We surveyed PCPs and patients about the aid's acceptability. Patients completed the SDM‐process scale (scores range 0–4) to rate the SDM quality experienced. Participants' comments were subject to thematic analysis. Results Of 10 PCP ‐participants, seven were female and four were community‐based. Of 30 patient‐participants, 22 (73%) were non‐Hispanic White, 9 (30%) had ≥ 2 Charlson comorbidities and mean age was 78.5 years ( SD 2.8). Nine PCPs agreed that the aid helped them with SDM and was easy‐to‐use; six felt it had too much information; and seven planned to continue using the aid. Patients rated the SDM ‐process highly (scores = 3.0 [ SD 0.9]) and we observed high SDM (mean OPTION5 = 77.9 [ SD 20.6]). Participants felt the aid was “empowering” and “helpful for decision‐making.” After SDM discussions, seven patients intended to stop screening, nine to screen less frequently, and 14 to continue screening regularly. Conclusions We developed a novel conversation aid that supports SDM about mammography screening with women ≥ 75 years. Lessons learned will guide revisions of a final tool for testing in a clinical trial.

Abstract Background: Esophageal Adenocarcinoma (EAC) continues to rise in incidence, with prognosis remaining poor despite advances in multimodality therapy. Several novel target agents are now being explored as an option for treating EAC. One potential target is heat shock protein 90 (Hsp90), a chaperone protein that is involved in many diverse biological processes including cell signaling, proliferation, and survival. Many of the client proteins are known oncoproteins that allow Hsp90 to stabilize cancer cell growth by supporting proliferation and preventing apoptosis. The isoform, Hsp90β, is constituently expressed, while Hsp90α is inducible during times of stress, with expression increased 2-10 fold in cancers. Our hypothesis is that Hsp90 inhibition, in combination with standard chemotherapeutic drugs, will cause EAC cancer cells to be more susceptible to apoptosis and reduce the rate of proliferation. Methods: EAC cell lines, OE19 and OE33, were used to evaluate the effects of Hsp90 inhibitor, AUY-922, in cancer cell growth and apoptosis. ELISA of WST-1 and BrdU were used to determine the effective dosage and assess proliferation. Pathway inhibition was evaluated by Western Blot of Hsp90α and Hsp70. OE19, OE33, and patient samples of EAC tumor and gastroesophageal reflux tissue were used to assess the gene expression of Hsp90 and several client protein pathways by reverse transcription polymerase chain reaction (RT-PCR). Results: The ED50 of AUY-922 was determined to be 30ηM. A combination of chemotherapeutic drugs, cisplatin and 5-fluorouracil (5-Fu), along with AUY-922 showed significantly decreased proliferation compared to untreated and single agent treated cell lines. Western blot demonstrated that Hsp90 was inhibited by AUY-922 treatment, by a decrease in expression of Hsp90α, and an increase in the expression of Hsp70. RT-PCR in the cell line treatment groups showed an impact on many client oncoproteins involved in cancer cell survival and Hsp90 was shown to be upregulated in tumor samples when compared to normal GERD samples. Conclusion: The use of Hsp90 inhibitor, AUY-922, leads to reduced Hsp90 pathway expression, resulting in a degradation of many Hsp90 client proteins involved in cancer genesis. Cell proliferation was decreased with AUY-922 treatment, with the greatest demonstrated effect when used in combination with cisplatin and 5-Fu. Therefore, Hsp90 inhibition may have an application in multimodal EAC chemotherapy. Citation Format: Christina L. Rotoloni, Jaclyn M. LaRosa, Michael J. Porter, Lori A. Kelly, Katherine Nega, Emily Wolfson, Yoshihiro Komastu, Juliann E. Kosovec, Pashtoon M. Kasi, Toshitaka Hoppo, Ali H. Zaidi, Blair A. Jobe. Enhanced efficacy of cisplatin and 5-fluorouracil combination with AUY-922 in esophageal adenocarcinoma cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A48.