The LISA randomized trial of a weight loss intervention in postmenopausal breast cancer

Abstract

Obesity has been associated with poor breast cancer (BC) outcomes. We investigated whether a standardized, telephone-based weight loss lifestyle intervention in the adjuvant setting would impact BC outcomes. We conducted a multicenter trial randomizing women 1:1 to mail-based educational material alone (control) or combined with a standardized, telephone-based lifestyle intervention that focused on diet, physical activity, and behavior and involved 19 calls over 2 years to achieve up to 10% weight loss. In all, 338 (of 2150 planned) T1-3, N0-3, M0 hormone receptor positive BC patients with body mass index (BMI) ≥24 kg/m 2 receiving adjuvant letrozole were randomized (enrolment ended due to funding loss). The primary outcome was disease-free survival (DFS); secondary outcome was Overall Survival (OS). At 8 years' median follow-up, in a planned analysis, DFS and OS were compared using the Kaplan-Meier method. Baseline BMI and other characteristics were similar between study arms. In all, 22 of 171 (12.9%) in the lifestyle intervention arm versus 30 of 167 (18.0%) in the education had DFS events; the hazard ratio (HR) was 0.71 (95% confidence interval [CI]: 0.41-1.24, p = 0.23). Although loss of funding reduced sample size, we view these hypothesis generating results as compatible with our hypothesis of a potential beneficial effect of a lifestyle intervention on DFS. They provide support for completion of ongoing randomized controlled trials of the effect of lifestyle interventions in BC outcomes.npj Breast Cancer (2020) 6:6 ; https://doi.

Associations of adiposity and weight change with recurrence and survival in breast cancer patients: a systematic review and meta-analysis

“…A Mendelian randomization study showed that higher adiposity was associated with lower survival in estrogen receptor (ER)-positive but not in ER-negative breast cancer patients [6]. Randomized controlled trials of weight loss interventions have been conducted [7,8], but no definitive evidence yet exists on whether these improve survival or reduce recurrence risk [9].…”

The Tumor Promotional Role of Adipocytes in the Breast Cancer Microenvironment and Macroenvironment

“…Several large studies indicate that weight loss is associated with a lower risk of breast cancer, 120,121 suggesting that reversing obesity may reduce breast cancer risk and extend disease-free survival. 122 Although this is great news, one concern is that animal studies have demonstrated obesogenic memory in which adipose tissue inflammation exists even after weight loss. 123 Preventing obesity from occurring in the first place may provide the greatest benefits to cancer incidences.…”

The Breast Cancer Weight Loss trial (Alliance A011401): A description and evidence for the lifestyle intervention

“…At 1 year, participants in these two studies achieved mean losses of 7.2% and 8.6%, respectively (10‐12). The LISA study adapted the DPP lifestyle intervention for women with breast cancer, providing a less intensive intervention, and produced a 5.5% weight loss at 1 year and a trend toward decreased disease‐free survival events in the intervention arm (6,23). The individual, aspirational weight‐loss goal of 10% was selected based on literature that has suggested this is achievable through diet and exercise weight‐loss programs, including in breast cancer survivors, and that it modulates relevant biomarkers related to breast cancer risk and recurrence (12,24‐26).…”