Screening MRI Does Not Increase Cancer Detection or Result in an Earlier Stage at Diagnosis for Patients with High-Risk Breast Lesions: A Propensity Score Analysis.

BACKGROUND: Guidelines recommend consideration of screening MRI for patients with high-risk breast lesions (HRLs), acknowledging limited data for this moderate-risk population. METHODS: This study identified patients with atypical ductal/lobular hyperplasia (ADH/ALH), lobular carcinoma in situ, (LCIS) or both evaluated at our high-risk clinic. Patients were categorized as having received screening mammography (MMG) alone vs. MMG and breast MRI (MMG+MRI). Inverse probability weighting based on propensity scores (PS) representing likelihood of MRI use was applied to Kaplan-Meier and Cox regression analyses to determine cancer detection and biopsy rates by screening group. RESULTS: Among 908 eligible patients, 699 (77%) patients with available follow-up data were analyzed (542 with ADH/ALH and 157 with LCIS). Of the 699 patients, 540 (77%) received MMG alone, and 159 (23%) received MMG + MRI. The median follow-up period was 25 months, during which a median of two MRIs were performed. After PS-weighting, the characteristics of each screening group were well-balanced with respect to age, race, body mass index (BMI), menopausal status, breast density, family history, HRL type, and chemoprevention use. The 4 year breast cancer detection rate was 3.6% with both MMG alone and MMG+MRI (p = 0.89). The breast biopsy rates were significantly higher with MMG+MRI (30.5% vs12.6%; hazard ratio [HR], 2.67; p < 0.001). All breast cancers were clinically node-negative and pathologic stage 0 or 1. Among five cancers in the MMG+MRI group, two were MRI-detected, two were MMG-detected, and one was detected on clinical exam. CONCLUSIONS: Screening MRI did not improve cancer detection, and cancer characteristics were favorable whether screened with MMG alone or MMG + MRI. These findings question the benefit of MRI for patients with HRL, although longer-term follow-up study is needed.

Initiation and tolerance of chemoprevention among women with high-risk breast lesions: the potential of low-dose tamoxifen.

PURPOSE: High-risk lesions (HRLs) of the breast are an indication for chemoprevention, yet uptake is low, largely due to concerns about side effects. In 2019, low-dose (5 mg) tamoxifen was demonstrated to reduce breast cancer risk with improved tolerance. We describe chemoprevention uptake in an academic clinic before and after the introduction of low-dose tamoxifen. METHODS: Females age ≥ 35 with HRLs who established care from April 2017 through January 2020 and eligible for chemoprevention were included. Rates of chemoprevention initiation before and after the introduction of low-dose tamoxifen (pre-2019 vs. post-2019) were compared with chi-squared tests. Logistic regression identified demographic and clinical factors associated with chemoprevention initiation. Kaplan-Meier methods determined the rates of discontinuation. RESULTS: Among 660 eligible females with HRLs, 22.7% initiated chemoprevention. Median time from first visit to chemoprevention initiation was 54 days (interquartile range (IQR): 0-209); 31.0% (46/150) started chemoprevention > 6 months after their initial visit. Chemoprevention uptake was not significantly different pre-2019 vs. post-2019 (21.2% vs. 26.3%, p = 0.16); however, post-2019, low-dose tamoxifen became the most popular option (41.5%, 34/82). On multivariable analyses, age and breast cancer family history were significantly associated with chemoprevention initiation. Discontinuation rates at 1 year were lowest for low-dose tamoxifen (6.7%) vs. tamoxifen 20 mg (15.0%), raloxifene (20.4%), or an aromatase inhibitor (20.0%). CONCLUSION: In this modern cohort, 22.7% of females with HRLs initiated chemoprevention with 31.0% initiating chemoprevention > 6 months after their first visit. Low-dose tamoxifen is now the most popular choice for chemoprevention, with low discontinuation rates at 1 year.

Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer Survivors (The AIM Trial): Rationale, Design, and Methods.

Background: Obesity is a significant contributor to breast cancer recurrence and mortality. A central mechanism by which obesity stimulates cancer progression is through chronic, low-grade inflammation in adipose tissue. Exercise interventions to target chronic inflammation has a potential to improve obesity- and breast cancer-related outcomes; however, no studies have investigated the roles of exercise in modulating adipose tissue inflammation in breast cancer survivors. Also, it is unclear which exercise prescription would be optimal to maximize the outcomes. Therefore, we designed a randomized controlled trial (Taking AIM at Breast Cancer: Targeting Adiposity and Inflammation with Movement to Improve Prognosis in Breast Cancer Survivors [AIM] Trial) to examine the mechanisms by which different modalities of exercise impact chronic inflammation as a biomarker of breast cancer prognosis. Methods: The AIM trial is a prospective, three-armed, phase II randomized controlled trial investigating the effects of a 16-week supervised circuit aerobic and resistance exercise (CARE) program versus a traditional aerobic and resistance exercise (TARE) program and attention control (AC) on adipose tissue inflammation in breast cancer survivors. 276 patients who are diagnosed with stage 0-III breast cancer, post-treatment, sedentary, and centrally obese are randomized to one of the three groups. The CARE and TARE groups participate in thrice-weekly supervised exercise sessions for 16 weeks. The AC group are offered the CARE program after the intervention period. The primary endpoint is adipose tissue inflammation assessed by core biopsy and blood draw. The secondary and tertiary endpoints are sarcopenic obesity, physical fitness and function, and patient reported outcomes. The exploratory outcomes are long-term breast cancer outcomes. Discussion: This is the first randomized controlled trial examining the effects of exercise on adipose tissue inflammation in obese, breast cancer survivors. Our findings are anticipated to contribute to a better understanding of exercise modalities and mechanisms on adipose tissue inflammation that can potentially improve breast cancer prognosis. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03091842 identifier [NCT#03091842].