This article is more than 5 years old. Information may no longer be current.
Cholesterol-lowering medication may reduce breast cancer recurrence risk
Click Here to Manage Email Alerts
Cholesterol-lowering medication decreased risk for recurrence in patients with hormone receptor–positive early-stage breast cancer when administered during adjuvant endocrine therapy, according to results of an observational study.
“Patients with breast cancer undergoing adjuvant endocrine treatment seem to benefit from concomitant medication with cholesterol-lowering drugs in terms of improved RFS,” Signe Borgquist, MD, PhD, from the division of oncology and pathology at Lund University in Sweden, told HemOnc Today.
Preclinical studies have shown cholesterol-lowering medication may attenuate signaling through the ER by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol.
Thus, Borgquist and colleagues hypothesized that cholesterol-lowering medication in combination with endocrine therapy may improve breast cancer outcomes.
The researchers used data from the Breast International Group 1-98 clinical trial after 8 years’ median follow-up from initiation of adjuvant endocrine therapy.
In that trial, 8,010 postmenopausal women diagnosed with early-stage ER–positive invasive breast cancer from 1998 to 2003 were randomly assigned to one of two options:
- two-arm option, in which 20 mg tamoxifen was compared with 2.5 mg letrozole for 5 years; or
- four-arm option, in which two sequential arms of tamoxifen for 2 years followed by letrozole for 3 years were compared with letrozole for 2 years followed by tamoxifen for 3 years.
Patients provided data on systemic levels of total cholesterol and cholesterol-lowering medication use at baseline and every 6 months up to 5.5 years. Researchers sought to determine cholesterol levels over time according to endocrine therapy, the association of prior cholesterol-lowering medication exposure at the beginning of endocrine therapy on breast cancer outcomes, time to initiation of cholesterol-lowering medication according to assigned endocrine therapy, and the effects of cholesterol-lowering medication initiated during endocrine therapy on breast cancer outcomes.
“Similar associations have been suggested in observational studies previously; however, our results are important because we have evaluated the associations in a randomized control trial setting where data quality is considered high,” Borgquist said.
In total, 637 patients (8%) had prior exposure to cholesterol-lowering medication at the start of endocrine therapy. These patients showed improved DFS (HR = 0.82; 95% CI, 0.68-0.99) and breast cancer recurrence risk (HR = 0.83; 95% CI, 0.65-1.06) compared with those not exposed to cholesterol-lowering medication.
A total of 7,326 patients were not exposed to cholesterol-lowering medication at the start of endocrine therapy. Of these, 789 (10.8%) initiated cholesterol-lowering medication during endocrine therapy, which included letrozole monotherapy (n = 318), sequential tamoxifen and letrozole (n = 189), sequential letrozole and tamoxifen (n = 176) and tamoxifen monotherapy (n = 106). By 5 years of treatment, approximately 5% of patients who received tamoxifen initiated cholesterol-lowering medication, compared with 18% of the letrozole arm, 15% of the tamoxifen–letrozole arm, and 14% of the letrozole–tamoxifen arm.
Marginal structural Cox models showed the initiation of cholesterol-lowering medication during endocrine therapy was associated with improved DFS (HR = 0.79; 95% CI, 0.66-0.95), breast cancer–free interval (HR = 0.76; 95% CI, 0.6-0.97) and distant recurrence–free interval (HR = 0.74; 95% CI, 0.56-0.97).
In analyses of the two monotherapy arms, initiation of cholesterol-lowering medication did not add benefit to clinical outcome for DFS (adjusted HR = 0.99; 95% CI, 0.56-1.74), breast cancer-free interval (adjusted HR = 0.85; 95% CI, 0.42-1.74) or distant RFS (adjusted HR = 0.57; 95% CI, 0.24-1.35) in the tamoxifen-only arm. In addition, there was a nonsignificant trend toward a benefit in DFS (adjusted HR = 0.66; 95% CI, 0.40-1.08), breast cancer–free interval (HR = 0.77; 95% CI, 0.40-1.48) and distant recurrence–free interval (adjusted HR = 0.7; 95% CI, 0.31-1.59) in the letrozole-only arm.
“The evidence from our observational study warrants consideration of a large prospective randomized clinical trial to confirm the value of cholesterol-lowering medication concomitant with endocrine treatment of breast cancer,” the researchers wrote. “Further elucidation of the effect upon outcome of the clinical interaction between cholesterol-lowering medication and endocrine agents — both widely used by patients with breast cancer — will provide exclusive insight to future trial changes.” – by Melinda Stevens
For more information:
Singe Borgquist, MD, PhD, can be reached at Lund University, Division of Oncology and Pathology, Clinical Sciences, Barngatan 2B, 221 85 Lund, Sweden; email: single.borgquist@med.lu.se.
Disclosures: Borgquist reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts