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Two new studies examining different aspirin doses in different cancers add to the mounting evidence for the drug's beneficial role in reducing cancer risk.

Data from the Nurses' Health studies found that women who regularly took low-dose aspirin had a 23% reduction in risk compared with aspirin non-users (HR 0.77, 95% CI 0.61-0.96), Mollie Barnard, ScD, of Huntsman Cancer Institute at the University of Utah, and colleagues reported.

And a 49% reduction in risk of was observed among those in the Nurses' Health Study and Health Professionals Follow-up Study with a history of long-term twice-weekly use of regular-dose aspirin (adjusted HR 0.51, 95% CI 0.34-0.77), according to Andrew T. Chan, MD, MPH, of Massachusetts General Hospital, and colleagues.

Both sets of hazard ratios reflected multivariable adjustment that included such factors as age, menopausal status, parity, and family history of cancer.

The pair of studies, published in JAMA Oncology, arrive at a time when other findings are questioning aspirin's role in the primary prevention of cardiovascular disease (CVD). In 2015, the U.S. Preventive Services Task Force backed the use of low-dose aspirin for the prevention of CVD and colorectal cancer.

"This is the strongest evidence to date that aspirin use can reduce the risk of HCC," wrote Victoria Seewaldt, MD, of City of Hope Comprehensive Cancer Center in Duarte, California, in an .

Seewaldt said the two studies "have the power to start to change clinical practice," but cautioned that the risk-benefit ratio must be considered when recommending aspirin.

"The potential benefits of aspirin must be weighed against the risk of bleeding, particularly in individuals with chronic liver disease," said Seewaldt. "To reach the full promise of aspirin's ability to prevent cancer, there needs to be better understanding of dose, duration, and mechanism."

Low-Dose Aspirin in Ovarian Cancer

"What really differentiated this study from prior work was that we were able to analyze low-dose aspirin separately from standard-dose aspirin," Barnard said in a . "Our findings emphasize that research on aspirin use and cancer risk must consider aspirin dose."

When Barnard's group looked at current aspirin use at any dose versus non-use, they found no association with ovarian cancer risk (HR 0.99, 95% CI 0.83-1.19). But the low-dose aspirin benefit was seen when they separated out the aspirin dosing (≤100 mg versus standard 325 mg). No reduction in ovarian cancer risk was seen with regular-dose aspirin (HR 1.17, 95% CI 0.92-1.49).

The investigators also noted significant positive trends for increasing cumulative weekly use (P=0.03 for trend) and duration of aspirin use (P=0.02 for trend).

"These findings suggest that the same low-dose, long-term aspirin regimens that are recommended for cardiovascular prophylaxis and colorectal cancer risk reduction can also reduce ovarian cancer risk," wrote Seewaldt in her editorial.

By contrast, use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) was tied to an increase in ovarian cancer risk (HR 1.19, 95% CI 1.00-1.41); no association was seen with acetaminophen use.

The study collected data on NSAID use and ovarian cancer diagnosis from the 1980-2014 Nurses' Health Study (n=93,664) and 1989-2015 Nurses' Health Study II (n=111,834). There were 1,054 incident cases of epithelial ovarian cancer across the two studies.

Standard-Dose Aspirin in HCC

"Regular use of aspirin led to significantly lower risk of developing HCC, compared to infrequent or no aspirin use, and we also found that the risk declined progressively with increasing aspirin dose and duration of use," co-author Tracey Simon, MD, of Massachusetts General Hospital in Boston, said in a .

When compared with no aspirin use, there indeed appeared to be a dose-dependent benefit with aspirin in reducing HCC risk (P=0.006 for trend):

• ≤1.5 tablets of regular-dose aspirin per week (adjusted HR 0.87, 95%CI 0.51-1.48)
• >1.5 to 5 tablets per week (adjusted HR 0.51, 95% CI 0.30-0.86)
• >5 tablets per week (adjusted HR 0.49, 95% CI 0.28-0.96)

And increasing duration of aspirin use (≥5 years) was significantly tied to lower HCC risk (P=0.03 for trend), most notably with ≥1.5 tablets of regular-dose aspirin per week (adjusted HR 0.41, 95% CI 0.21-0.77).

"The long duration of aspirin use could be necessary because primary liver cancer takes many years to grow," Simon said. "Aspirin may act at the earliest stages of cancer development, or even at precancerous stages, by delaying or preventing inflammation or liver fibrosis."

The researchers found no association between use of NSAIDs and HCC risk (adjusted HR 1.09, 95% CI 0.78-1.51).

"Since regular aspirin use carries the risk of increased bleeding, the next step should be to study its impact in populations with established liver disease, since that group is already at risk for primary liver cancer," said Simon.

The researchers conducted a pooled analysis of the Nurses' Health Study, which enrolled over 120,000 women ages 30 to 55; and the Health Professionals Follow-up Study, which enrolled over 50,000 men ages 40 to 75. Both prospective studies were conducted in the U.S.

Between the two studies, 133,371 individuals were included -- those who reported data on their frequency, dose, and duration of aspirin use. There were 108 incident cases of HCC in the 26 years of follow-up.