Author: Megan Brooks
Iniitiating statins within 3 years of diagnosis of early-stage breast cancer was associated with a modest but clinically meaningful 10% lower risk of dying from breast cancer and an 8% lower risk of dying from any cause, a recent Danish registry study suggests.
The researchers calculated that 59 patients would need to take statins to prevent one additional breast cancer death at 10 years.
“Clinically, this means that if a patient is prescribed statins after diagnosis for cardiovascular reasons, there is no reason to stop them — in fact, there may be added benefit,” first author Sixten Harborg, MD, Department of Oncology, Aarhus University Hospital, Aarhus, Denmark, told Medscape Medical News.
Harborg added that, “while we are not recommending statins as part of cancer treatment yet, the results are encouraging, especially as we wait for randomized trial data from the MASTER trial,” which is evaluating the addition of the statin atorvastatin to standard adjuvant therapy in early breast cancer.
Plausible Anticancer Effects
Statins have demonstrated benefits beyond lowering cholesterol and preventing cardiovascular events. The drugs have anti-inflammatory properties and can inhibit cell growth as well as enhance or suppress immune activity. Preclinical studies have suggested that elevated cholesterol may fuel tumor growth in breast cancer, and that statins can inhibit cancer cell proliferation, induce apoptosis, and mitigate metastasis.
However, physicians often discontinue statins following a breast cancer diagnosis over a “misconception that they are irrelevant in the context of malignant disease,” Harborg and colleagues noted in their paper online, published in JAMA Network Open.
In the current analysis, Harborg and colleagues evaluated the association between post-diagnosis statin initiation and breast cancer mortality using an emulated target trial approach — an advanced statistical method that uses observational data to mimic the design and analysis of a randomized controlled trial.
Using Danish registry data, the researchers identified 66,952 women with stage I-III breast cancer, none of whom had prior invasive breast cancer or had taken a statin within 1 year before enrollment.
To emulate a target trial of statin use after a breast cancer diagnosis, theresearchers created a clone of each patient — one assigned to a statin-initiation strategy and one to a nonstatin group — with censoring based on statin use during a 3-year grace period. This cloning approach ensured that both groups were identical at baseline, with censoring rules applied based on whether and when patients started statin therapy within a 3-year window. Participants were followed for up to 10 years or until death, emigration, or deviation from their assigned treatment strategy.
Over a median follow-up of 9 years, 4851 women began statin therapy. During more than 600,000 person-years of observation, 9130 participants died from breast cancer and 19,679 from any cause.
The 10-year risk for breast cancer mortality was lower in statin initiators than in noninitiators — 11.8% vs 13.5% (risk difference, 1.7%). Overall, 59 patients would need to receive a statin to prevent one additional breast cancer death (hazard ratio [HR], 0.90).
A similar difference in all-cause mortality was reported among statin users — 23.3% vs 24.5% (risk difference, 1.2%; HR, 0.92).
The survival advantage was greatest in women who started statins soon after diagnosis. Those initiating a statin within 12 months had a 28% lower risk of dying from breast cancer (HR, 0.72) than noninitiators. Similarly, patients who initiated statins within 24 months after diagnosis had a lower risk for breast cancer mortality (HR, 0.83) and all-cause mortality (HR, 0.87).
The statin benefit was consistent across most subgroups, including those with node-positive breast cancer, those with estrogen receptor (ER)-positive or ER-negative tumors, as well as those receiving different combinations of surgery, radiotherapy, chemotherapy, or endocrine therapy.
The findings are “intriguing” and point to the “potential” role for statins in patients with breast cancer, said Naomi Y. Ko, MD, MPH, medical oncologist and section chief of the breast oncology program at NYU Langone Perlmutter Cancer Center in New York City, who wasn’t involved in the research.
While it’s “certainly plausible” that statins can improve breast cancer outcomes, Ko said, “the challenge with the study is that the group that had the statins already had better prognosis, given that they had smaller tumors and lower grade tumors. Those characteristics alone would give them an improved prognosis.”
Ko highlighted the need to individualize statin use among patients. If, for instance, a patient is on a statin with an indication of high cholesterol, “I will support her taking those medications,” Ko said. Additionally, because aromatase inhibitors can raise cholesterol levels, it’s important to check cholesterol levels after starting these drugs and if there is an indication to start a statin, “I support it.”
Overall, the study helps increase awareness of the possible benefits of statins among patients with early breast cancer, but “I certainly would need to see more research before I would support universal treatment with statins for all breast cancer patients,” Ko said.
The study was supported by Aarhus University, the Novo Nordisk Foundation, Director Michael H. Nielsens Memorial Grant, Fabricant Einar Willumsens Memorial Grant, Astrid Thaysens Grant for Medical Research, Eva and Henry Frænkels Memorial Grant, ESMO Merit Travel Grant Award, and the Danish Cancer Society. Harborg and Ko had no disclosures.