Breast Cancer Deaths Lower With Statin Therapy, Taiwanese Data Hint

Statin use is linked to better survival in breast cancer, observational data from Taiwan suggest. Yet researchers only saw a difference for all-cause and cancer-related deaths, not CV death.

The results, from a propensity-score-matched analysis of more than 14,000 patients, were published recently in JAMA Network Open.

It’s well established that statins can “reduce blood cholesterol, mitigate atherosclerosis, and improve cardiovascular outcomes,” Wei-Ting Chang, MD (Chi-Mei Medical Center, Tainan, Taiwan), and colleagues note. The drug class also has drawn attention for its pleiotropic effects, most notably its ability to reduce inflammation. In the cancer realm, it’s been proposed that statins could be antiproliferative as well.

This isn’t the first study to tie statin therapy to cancer survival, but “in contrast to Western patients with breast cancer, Asian patients are relatively younger at diagnosis, and a large proportion are premenopausal and have few cardiovascular risk factor,” Chang et al explain.

Daniel Lenihan, MD (Saint Francis Healthcare System, Cape Girardeau, MO), immediate past president of the International CardioOncology Society, said that while the concept of statins possibly holding benefit in cancer isn’t new, people outside the cardio-oncology space still “might sort of raise an eyebrow” at the idea.

It’s “very plausible” that statins could be making this much of a dent in cancer-related death, Lenihan told TCTMD, citing a 2012 paper by Cleveland Clinic researchers that showed, retrospectively, that women with breast cancer treated with anthracycline-based chemotherapy had better heart failure-free survival if they were on statin therapy. Though more proof-of-concept than definitive, he added, “it was a very meaningful initial report.”

That work has been followed by other studies with mixed results, but survival signals of better cancer outcomes also have been seen in other cancer types, like multiple myeloma, Lenihan said.

Then there’s the added fact that the chemotherapy used to treat cancer can have the side effect of harming the heart. Here, too, it’s been suggested statins could help.

In late 2022, the small, randomized PREVENT trial failed to show a cardioprotective effect of statins in breast cancer and lymphoma patients with no existing indication for statin therapy. On its heels in early 2023, however, came another small but randomized trial, STOP-CA, which suggested that atorvastatin might protect against ventricular dysfunction in lymphoma patients receiving chemotherapy with anthracyclines.

Tomas G. Neilan, MD (Massachusetts General Hospital, Boston), principal investigator for STOP-CA, commenting on the current analysis for TCTMD, stressed that his perspective is that of a cardiologist. This study from Taiwan, by virtue of looking at cancer outcomes, is more tied to oncology, he noted.

With that caveat, “I think most of us would agree that there are no data to suggest that statins have an adverse impact on cancer outcomes, and there’s some nice plausibility that statins may be beneficial from a cancer-outcome perspective. But all the data that may suggest a beneficial role have been retrospective, observational” studies, with the few existing, small trials showing no effects, said Neilan.

W. Gregory Hundley, MD (Virginia Commonwealth University, Richmond), principal investigator of PREVENT, agreed the current report joins a long line of others supporting statins’ link to cancer survival. It appears “statins may amplify the effectiveness of cancer treatments,” Hundley commented to TCTMD. And there is no evidence of negative impact, in breast cancer at least, on survival from the initial disease or risk of recurrence, he added.

Cancer-Related Death but Not CV Death

Using the Taiwanese National Health Insurance Database and National Cancer Registry, Chang and colleagues identified 63,530 female patients with breast cancer between 2012 and 2017. Among them, 12.2% had been taking statins 6 months prior to their diagnosis.

There were no differences in cancer stage, cancer treatments, or socioeconomic status by status use. On the whole, the women on statins tended to be older (mean age 65 vs 54 years); had more coronary artery disease (17% vs 3%), hypertension (66% vs 19%), and diabetes (51% vs 7%); and were more likely to be taking an ACE inhibitor/ARB (47% vs 10%) or antiplatelet therapy (21% vs 3%).

The researchers used propensity-score matching to account for imbalances in year of diagnosis, age, cancer stage, anticancer therapies, comorbidities, socioeconomic status, and use of cardiovascular drugs before enrollment, so that they were able to compare 7,451 statin users and 7,451 nonusers. In the matched analysis, 15.63% of patients died. The cancer-related death rate was 11.09%, as compared with a cardiovascular death rate of just 0.85%.

Statin use was associated with a lower risk of all-cause death (adjusted HR 0.83; 95% 0.77-0.91), a difference driven by cancer-related death (adjusted HR 0.83; 95% CI 0.75-0.92). There was no relationship between statin use and cardiovascular death.

Contrary to STOP-CA, there was no sign that statins were exerting a protective effect against chemotherapy-induced heart damage, with no significant differences seen between the statin and no-statin groups in the risks of heart failure, arterial events (acute MI and ischemic stroke), or venous events (pulmonary embolism and deep vein thrombosis).

Overall, “our findings provide evidence to support the use of statins in patients with breast cancer; however, randomized studies are necessary,” the researchers conclude.

As for why there was no reduction in CV death risk, Lenihan said this may be simply because these deaths are undercounted. “If you have a cancer and are being treated for cancer, they’re going to follow the cancer really closely. If someone dies for some other reason, they don’t really explore what the reason is,” he pointed out. The mean age of the women studied was also relatively young—mid-60s—when deaths from CVD would have been rare.

Neilan, for his part, observed that the two groups studied—statins and no statins—weren’t equally matched from a cardiovascular perspective, which can be hard to fully adjust for, and that the event rates were “relatively low, so I would urge caution in the interpretation of that.”