Jeanne S Mandelblatt’s research while affiliated with Georgetown University Medical Center and other places

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.

Endocrine therapy for breast cancer may reduce the risk of contralateral breast cancer (CBC). However, there are no published estimates quantifying the lifetime outcomes by age at primary diagnosis, regimen, or duration. Here, we adapted an established Cancer Intervention and Surveillance Network (CISNET) model to simulate life histories of multiple US female birth-cohorts diagnosed with stage 0-III ER+/HER2- breast cancer receiving different durations (none, 2.5, 5, 10 years) of two endocrine therapy regimens (aromatase inhibitors or tamoxifen; including ovarian-function suppression for premenopausal women). As expected, greater duration of endocrine therapy led to more avoided CBC cases, as did aromatase inhibitors over tamoxifen, but the numbers varied greatly by the age of diagnosis. The maximum number of CBC were avoided using 10-year aromatase inhibitor regimens (6.0 vs. 11.2 for no adjuvant therapy, per 100 women with ER+/HER2- breast cancer). For the 5-year aromatase inhibitors therapy, women <45 years had the largest reduction in CBC cases (5.0/100), which dropped to 2.7/100 for women at 75+ years. Quantification of the lifetime risk of CBC for specific endocrine therapy types and duration is helpful for weighing therapeutic options. The risk of breast cancer death has a larger weight, but inclusion of the risk of CBC increases the separation between different therapy options.

Cancer-related cognitive impairment (CRCI) is a common side effect of cancer and its treatments. Cancer chemotherapy has been associated with hippocampal dysfunction and memory impairment. We investigated the effects of one chemotherapy agent, doxorubicin, on the transcription factor Ascl1 and proliferation of stem cells in the brain. We used an inducible mouse model designed to express TdTomato in Ascl1-lineage cells. Five to six-month-old Ascl1-CreERT2:ROSA mice were treated peripherally with a single dose of either doxorubicin (10 mg/kg) or DMSO control (n = 9 per group, n = 4–5 per sex). We analyzed brains of mice that had been exposed to doxorubicin for 2 weeks and had induced Ascl1 expression after the first week. We used immunostaining of neurogenesis stage specific markers to evaluate the doxorubicin effects on neuronal differentiation in the dentate gyrus of the hippocampus. Overall, doxorubicin significantly increased Ascl1 expression by 81% at this time point. As measured by Ascl1 double stains with Sox2, GFAP, and NeuroD1, doxorubicin-treated mice experienced an increase in Ascl1-mediated neural proliferation compared to control. A similar significant increase in the number of Ascl1-expressing cells (by 146%) after doxorubicin treatment was observed in the gray matter of the cerebral cortex. Thus, rather than leading to the loss of developing neurons, we found that a single dose of doxorubicin increased their appearance and progression, suggesting that hippocampal losses from chemotherapies may require greater and more sustained damage.

Importance Cancer mortality has decreased over time, but the contributions of different interventions across the cancer control continuum to averting cancer deaths have not been systematically evaluated across major cancer sites. Objective To quantify the contributions of prevention, screening (to remove precursors [interception] or early detection), and treatment to cumulative number of cancer deaths averted from 1975 to 2020 for breast, cervical, colorectal, lung, and prostate cancers. Design, Setting, and Participants In this model-based study using population-level cancer mortality data, outputs from published models developed by the Cancer Intervention and Surveillance Modeling Network were extended to quantify cancer deaths averted through 2020. Model inputs were based on national data on risk factors, cancer incidence, cancer survival, and mortality due to other causes, and dissemination and effects of prevention, screening (for interception and early detection), and treatment. Simulated or modeled data using parameters derived from multiple birth cohorts of the US population were used. Interventions Primary prevention via smoking reduction (lung), screening for interception (cervix and colorectal) or early detection (breast, cervix, colorectal, and prostate), and therapy (breast, colorectal, lung, and prostate). Main Outcomes and Measures The estimated cumulative number of cancer deaths averted with interventions vs no advances. Results An estimated 5.94 million cancer deaths were averted for breast, cervical, colorectal, lung, and prostate cancers combined. Cancer prevention and screening efforts averted 8 of 10 of these deaths (4.75 million averted deaths). The contribution of each intervention varied by cancer site. Screening accounted for 25% of breast cancer deaths averted. Averted cervical cancer deaths were nearly completely averted through screening and removal of cancer precursors as treatment advances were modest during the study period. Averted colorectal cancer deaths were averted because of screening and removal of precancerous polyps or early detection in 79% and treatment advances in 21%. Most lung cancer deaths were avoided by smoking reduction (98%) because screening uptake was low and treatment largely palliative before 2014. Screening contributed to 56% of averted prostate cancer deaths. Conclusions and Relevance Over the past 45 years, cancer prevention and screening accounted for most cancer deaths averted for these causes; however, their contribution varied by cancer site according to these models using population-level cancer mortality data. Despite progress, efforts to reduce the US cancer burden will require increased dissemination of effective interventions and new technologies and discoveries.

352 Background: Frailty contributes to healthcare expenditures. Cancer and its therapies can further increase or accelerate the rate of frailty. Addressing geriatric deficits contributing to frailty of older cancer survivors (ages 65+) could potentially reduce health expenditures. However, little is known about how frailty affects health expenditures during the continuing survivorship period, a period after initial treatment but before the end-of-life. Given that older adults with cancer can live for years, it is important to examine health expenditures during this period by levels of frailty. Methods: We used the 2-year longitudinal panels of the Medical Expenditure Panel Survey, a nationally representative survey, to identify cancer survivors who are likely in the continuing survivorship period. We created 5 cohorts who were surveyed in 2016, 2017, 2019, 2020, and 2021, and in the previous year. In each cohort, we selected older individuals with an invasive cancer diagnosis in both previous and current years who did not die in the current year. We pooled the cohorts to estimate annual healthcare expenditures, representing a cancer population of 11,802,386 in the US (n=2,206). We constructed a deficit accumulation frailty index using survey items and divided patients into 3 categories: robust, pre-frail, and frail. We used generalized linear regression to estimate the associations of frailty with annual healthcare expenditures during the continuing survivorship period for older adults, controlling for age, sex, race/ethnicity, marital status, immigration background, insurance coverage, family size, family income, and education. Costs were inflated to 2023 US dollars. Results: The per person annual healthcare expenditure among older adult survivors of all cancer types was 13499.13, 24698.77, and $34352.23 for those who were robust (75.2%), pre-frail (12.0%), and frail (12.8%), respectively, and being pre-frail and frail was associated with higher expenditures (P<0.001). In analyses by cancer type, being frail (vs. robust) was associated with higher expenditures for bladder (P<0.05), breast (P<0.01), cervical (P<0.01), and prostate (P<0.01) cancers. Pre-frail breast cancer patients also incurred more costs than those who were robust (P<0.01). Conclusions: Increased frailty was associated with higher annual healthcare expenditures among older cancer survivors during the continuing survivorship period. Addressing geriatric deficits and intervening to maintain function and prevent frailty progression during survivorship care could improve quality of life and reduce healthcare expenditures.

Background Black individuals with cancer have a higher prevalence of comorbidities and a worse cancer prognosis than other racial groups in the US. As part of a quality improvement project, we aimed to demonstrate feasibility of self-monitoring and community health worker (CHW) support among managing comorbidities for Black individuals with breast or prostate cancer. Methods In a single arm, pre-post study, we enrolled patients with diabetes and/or hypertension who identified as Black and were diagnosed with 1) stage 0-IV breast cancer, or 2) prostate cancer and on long-term androgen-deprivation therapy. Participants received a home-monitoring device linked to a mobile app and worked with a CHW over six months to track their blood pressure (BP) and/or blood glucose (BG). PROMIS surveys assessed support and self-efficacy. Results Between May 2021–December 2022, 61 patients with breast or prostate cancer comorbid with hypertension (79 %) or hypertension and diabetes (21 %) enrolled. Once weekly self-recording of BP and BG was achieved in 92 % of individuals (with hypertension) and 77 % of individuals (with diabetes and hypertension). Participants (n = 47) who reported ≥4 readings in Months 1 and 6 demonstrated improved BP control (mean reduction = 4.07 mmHg); too few BG readings were collected to assess change. We observed a slight decrease in PROMIS scores for informational (mean 3.2, sd 8.0) and instrumental support (mean 3.6, sd 8.3). Conclusions A self-monitoring and CHW intervention is a feasible approach to monitor hypertension among Black cancer patients. Modifications are needed to improve BG monitoring and patient reported outcomes.

The central premise of this article is that a portion of the established relationships between social determinants of health and racial/ethnic disparities in cancer morbidity and mortality are mediated through differences in rates of biological aging processes. We further posit that using knowledge about aging could enable discovery and testing of new mechanism-based pharmaceutical and behavioral interventions (“gerotherapeutics”) to differentially improve the health of minoritized cancer survivors and reduce cancer disparities. These hypotheses are based on evidence that lifelong differences in adverse social determinants of health contribute to disparities in rates of biological aging (“social determinants of aging”), with minoritized groups having accelerated aging (ie, a steeper slope or trajectory of biological aging over time relative to chronological age) more often than non-minoritized groups. Acceleration of biological aging can increase the risk, age of onset, aggressivity and/or stage of many adult cancers. There are also documented negative feedback loops whereby the cellular damage caused by cancer and its therapies act as drivers of additional biological aging. Together, these dynamic intersectional forces can contribute to differences in cancer outcomes between minoritized vs non-minoritized survivor populations. We highlight key targetable biological aging mechanisms with potential applications to reducing cancer disparities and discuss methodological considerations for pre-clinical and clinical testing of the impact of gerotherapeutics on cancer outcomes in minoritized populations. Ultimately, the promise of reducing cancer disparities will require broad societal policy changes that address the structural causes of accelerated biological aging and ensure equitable access to all new cancer control paradigms.