Adding a statin to endocrine therapy tied to improved breast cancer outcomes

By Reuters Staff

NEW YORK (Reuters Health) – Starting cholesterol-lowering therapy with adjuvant endocrine therapy was associated with clinical outcome for patients with ER-positive breast cancer in the BIG 1-98 clinical trial, researchers have found.

Based on this observational evidence, they say a large prospective randomized clinical trial should be considered to confirm the value of cholesterol-lowering medication in concert with endocrine treatment of breast cancer.

“The possible anticancer effects of cholesterol-lowering medication (CLM), including statins, may indirectly affect tumors through the systemic lowering of cholesterol levels and accompanying reduced levels of the cholesterol metabolite 27-hydroxycholesterol (27HC). 27HC acts as an estrogen receptor (ER) ligand and has been shown to regulate ER-dependent tumor growth,” Dr. Signe Borgquist of Lund University in Sweden and colleagues explain in a report online February 13 in the Journal of Clinical Oncology.

They investigated the impact of CLM in combination with endocrine therapy on breast-cancer outcomes in the BIG 1-98 trial of postmenopausal women with early-stage, ER-positive breast cancer. As part of the trial, 318 women were randomly assigned to letrozole monotherapy, 106 to tamoxifen monotherapy, 189 to sequential tamoxifen-letrozole and 176 to sequential letrozole-tamoxifen.

Prior exposure to CLM at the start of endocrine therapy (compared with no prior exposure) was associated with improved disease-free survival (adjusted hazard ratio 0.82; 95% confidence interval, 0.68 to 0.99), breast cancer recurrence (HR, 0.83; 95% CI, 0.65 to 1.06), distant recurrence-free interval (HR, 0.81; 95% CI, 0.61 to 1.09).

Starting CLM during any endocrine therapy was also associated with improved disease-free survival (HR, 0.79; 95% CI, 0.66 to 0.95), breast cancer-free interval (HR, 0.76; 95% CI, 0.60 to 0.97), and distant recurrence-free interval (HR, 0.74; 95% CI, 0.56 to 0.97).

In analyses of the two monotherapy arms, women treated with tamoxifen alone did not appear to benefit from starting a cholesterol-lowering drug. However, the “low numbers of patients in these analyses limit the interpretation of these results,” the researchers say.

“Several registry-based studies have reported protective associations between CLM (statins in particular) and outcomes among women with ER-positive breast cancer,” Dr. Borgquist and colleagues point out.

However, to the best of their knowledge, “this study is the first to support the beneficial effect of CLM on breast cancer outcome that is based on a large, international, prospectively conducted, randomized clinical trial of modern adjuvant endocrine therapy in postmenopausal women with ER-positive breast cancer.”

“Future studies assessing CLM use among patients with breast cancer who are receiving endocrine treatment may enrich our understanding of factors that influence the effectiveness of endocrine therapy and the role of CLM in treating breast cancer,” they write.

SOURCE: http://bit.ly/2lJezrG

J Clin Oncol 2017.

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