Cholesterol-Lowering Therapy May Boost Breast Cancer Endocrine Therapy Benefits

Cholesterol-lowering medication might have a role in reducing breast cancer recurrence among postmenopausal women undergoing endocrine therapy

medwireNews: Combining adjuvant endocrine therapy with a cholesterol-lowering medication (CLM) could further reduce the risk of recurrent breast cancer, indicate Breast International Group (BIG) 1-98 study findings from postmenopausal women treated for operable, invasive hormone receptor-positive disease.

CLM has been hypothesized to have an anticancer impact by both lowering levels of the cholesterol metabolite 27-hydroxycholesterol, which can alter tumour growth via oestrogen receptor (ER) binding, and by reducing cholesterol availability during tumour growth.

 “Thus, assessment of both statins and other CLMs is necessary when evaluating the potential impact of systemic cholesterol reduction on breast cancer outcomes”, explain Signe Borgquist, from Lund University in Sweden, and co-workers.

Cholesterol levels were reported at 6-month intervals for 5944 CLM-naive participants of the phase III study, 697 of whom initiated CLM during a 5-year course of endocrine therapy. CLM was used by 5% of patients assigned to receive tamoxifen  monotherapy, 18% of patients given letrozole monotherapy, 15% of those given tamoxifen followed by letrozole and 14% given letrozole followed by tamoxifen.

Patients who began CLM during endocrine treatment had significantly better disease-free survival than those who did not (hazard ratio [HR]=0.79) after adjusting for tumour features and treatment, the researchers report.

CLM initiation was also associated with a significantly longer breast cancer-free interval (HR=0.76) and a longer time without distant recurrence (HR=0.74).

Noting that aromatase inhibitor use is associated with hypercholesterolaemia, which may reduce the efficacy of endocrine therapy via the ER binding mechanism, the authors hypothesized that “CLM initiation may be especially relevant for patients receiving letrozole”.

Whereas, they explain, “tamoxifen reduces cholesterol levels and concomitant CLM may have less clinical impact.”

Exploring these relationships further in the monotherapy groups, the team found that concomitant CLM use had no significant influence on the three survival outcomes for patients given tamoxifen monotherapy.

And, as predicted, the researchers identified survival benefits for CLM use with letrozole alone that were “comparable in magnitude to the overall effect of CLM initiation”, although these did not reach statistical significance.

“We recognize, however, that low numbers of patients in these analyses limit the interpretation of these results”, the authors caution in the Journal of Clinical Oncology.

The BIG 1-98 investigators conclude: “The evidence from our observational study warrants consideration of a large prospective randomized clinical trial to confirm the value of CLM concomitant with endocrine treatment of breast cancer.

“Further elucidation of the effect upon outcome of the clinical interaction between CLM and endocrine agents—both widely used by patients with breast cancer—will provide exclusive insight to future trial designs.”


Borgquist S, Giobbie-Hurder A, Ahern TP, et al. Cholesterol, cholesterol-lowering medication use, and breast cancer outcome in the BIG 1-98 Study. J Clin Oncol; Advance online publication 13 February 2017. DOI: 10.1200/JCO.2016.70.3116

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