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SAN ANTONIO -- Inflammatory breast cancer grew significantly more slowly in women who had a history of treatment with statin drugs, findings from a large retrospective review showed.

Overall, statin use was associated with significant improvement in progression-free survival (PFS). Analysis by type of statin showed that outcomes with hydrophilic agents drove the results, Naoto Ueno, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, reported here at the San Antonio Breast Cancer Symposium.

Patients who used hydrophilic statins had a median PFS of almost 5 years, compared with 2.47 years among patients who took lipophilic statins and 1.76 years for women who had no history of statin use.

The benefit did not extend to overall survival, but treatment with hydrophilic statins was associated with about a 6-month improvement in disease-specific survival (DSS) compared with no statin use.

The results add to other evidence that statins favorably affect breast cancer risk or outcomes, but the potential role of the drugs in managing breast cancer has yet to be determined, Ueno said.

"We did this study because there was a paper by a European group that showed that statins will reduce breast cancer incidence," Ueno told 口袋女优. "But once again, that was not tested in a randomized, prospective manner. It's time to test, in a certain patient population, whether statins have any role."

Used primarily to treat lipid disorders, statins have well-documented pleiotropic effects, including anti-inflammatory activity. The drugs' multiple, diverse effects have led to speculation that statins might be beneficial in certain types of cancer.

The speculation has extended to potential differential effects according to the solubility of statins (hydrophilic or lipophilic). A recent Danish study, which Ueno referenced, showed a significant reduction in the risk breast cancer recurrence among users of lipophilic statins (J Natl Cancer Inst. 2011; 103: 1461-1468).

Inflammatory breast cancer is an uncommon but exceptionally aggressive form of breast cancer. The inflammatory nature of the disease results from cancer cells' migration into and eventual obstruction of lymphatic vessels. Ueno and colleagues hypothesized that statins would improve outcomes in patients with inflammatory breast cancer.

The investigators reviewed medical records of 724 patients with diagnoses of inflammatory breast cancer seen at MD Anderson from 1995 to 2011. They compared outcomes according to statin use, including type of statin. Outcomes of interest were PFS, DSS, and overall survival.

The analysis showed numerical advantages for use of hydrophilic statins across all of the endpoints. Median values in years were:

• PFS -- 4.88 (hydrophilic), 2.47 (lipophilic), 1.76 (no statin), P=0.04
• DSS -- 5.10, 3.79, 4.52 (NS)
• Overall survival -- 5.05, 3.79, 4.32 (NS)

In a multivariate analysis adjusted for radiotherapy, hormone-receptor status, and HER2 status, a history of treatment with a hydrophilic statin was associated with 51% reduction in the hazard for progression (HR 0.49, P<0.01).

In a model adjusted for lymphovascular invasion, nuclear grade, and surgical status at 1 year, a history of hydrophilic statin therapy (versus no statin use) was associated with a 20% reduction in mortality risk and a 15% reduction in disease-specific mortality, neither of which achieved statistical significance.

Ueno had no explanation for why the MD Anderson and Danish results differed by type of statin use, although he pointed out that the Danish study was not limited to inflammatory breast cancer. He said the contradiction supports an argument for randomized clinical trials to examine the effects of statin therapy on breast cancer outcomes.

"Even though we evaluated hydrophilic versus lipophilic statins, I think the effects [on cancer] will come down to individual drugs," said Ueno. "Specifically, I think it will come down to whether simvastatin or atorvastatin has more of an effect on cancer."

Ueno and colleagues have written a protocol and are seeking funding for a randomized clinical trial to compare the two statins' effects on breast cancer recurrence and overall survival.

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