Cholesterol-Lowering Medications Complement Endocrine Therapy in Breast Cancer

Including anti-cholesterol agents during adjuvant endocrine treatment can prevent breast cancer recurrence in hormone receptor—positive early-stage breast cancer. These are the findings of an observational study published in the Journal of Clinical Oncology that analyzed phase 3 data from the BIG 1-98 trial.

Between 1998 and 2003, the Breast International Group (BIG) enrolled 8010 postmenopausal women with early-stage, estrogen receptor—positive invasive breast cancer. Patients in the 2-arm part of the study received either 20 mg tamoxifen daily or 2.5 mg letrozole (an aromatase inhibitor) daily, for 5 years. The 4-arm option included 2 sequential arms of tamoxifen for 2 years and then letrozole for 3 years or, letrozole for 2 years followed by tamoxifen for 3 years.

Study end points were disease-free survival (DFS), breast cancer—free interval (BCFI), and distant recurrence–free interval (DRFI). Total cholesterol levels were measured at baseline, when the patient enrolled in the study, and then every 6 months for up to 5.5 years.

The authors observed an influence of tamoxifen on serum cholesterol levels, which reduced during tamoxifen treatment and rose back up once treatment stopped—irrespective of whether tamoxifen was administered alone, prior to, or after letrozole. However, letrozole did not have any effect on cholesterol levels.

Only a small proportion (8%) of the 7963 patients who received at least 1 dose of the study therapy, reported prior exposure to a cholesterol-lowering drug when they started endocrine treatment. These patients were typically older, nonsmokers, had diabetes, a cardiac medical history, smaller tumors, and fewer positive lymph nodes at diagnosis. Compared with the remaining 92% of patients not exposed to anti-cholesterol medication, these patients had,

• 18% reduction in DFS hazard (DFS hazard ratio [HR]_adj, 0.82; 95% CI, 0.68 to 0.99)
• 17% reduction in disease recurrence (BFCI HR_adj, 0.83; 95% CI, 0.65 to 1.06)
• 19% lower hazard of distant recurrence (DRFI HR_adj, 0.81; 95% CI, 0.61 to 1.09

Of the majority of patients who started on a cholesterol-lowering drug for the first time during the trial, 5% who were receiving tamoxifen had started on these drugs by 5 years of treatment, which was much higher than those receiving letrozole. These anti-cholesterol agents, the authors found, improved all 3 outcomes being evaluated: DFS (HR_adj, 0.79; 95% CI, 0.66 to 0.95; P = .01), BCFI (HR_adj, 0.76; 95% CI, 0.60 to 0.97; P = .02), and DRFI (HR_adj, 0.74; 95% CI, 0.56 to 0.97; P = .03).

For patients in the monotherapy arms, initiating anti-cholesterol medication had no significantly beneficial effect for patients receiving either tamoxifen or letrozole.

The results indicate that baseline use of anti-cholesterol medication improves outcomes in patients with breast cancer receiving endocrine treatment. However, patients receiving the aromatase inhibitor letrozole seemed to benefit more than others if they received cholesterol-lowering drugs during endocrine treatment.

Reference

Borgquist S, Giobbie-Hurder A, Ahern TP, et al. Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 study [published online February 13, 2017]. J Clin Oncol. doi: 10.1200/JCO.2016.70.3116.