medwireNews: Research suggests that women who use hormone-modulating breast cancer treatments (HMTs) such as tamoxifen or aromatase inhibitors (AIs) may experience a reduced risk for neurodegenerative disease (NDD).
“As we advance in our abilities to prevent, treat, and cure cancer, discussions around optimal care will need to include understanding the long-term outcomes of therapy selection for age-related NDDs,” explain Roberta Diaz Brinton, from the University of Arizona in Tucson, USA, and co-investigators.
“The fact that breast cancer is the second most common cancer in women (after skin cancer) and that women are disproportionately affected by AD [Alzheimer’s disease] and related dementia provides us with an opportunity to reduce the global disease burden of NDDs.”
The team analyzed information for 57,843 US breast cancer patients aged 45 years or older. The women were registered in the Humana insurance claims database between 2007 and 2017, and followed up for a mean of 5.5 years.
Around a third (31.3%) of these patients received tamoxifen, raloxifene, nonsteroidal AIs (anastrozole or letrozole), or a steroidal AI (exemestane), the researchers say in JAMA Network Open.
Propensity score-matched analysis revealed that women who received HMT were significantly less likely to be diagnosed with a NDD than those who did not, at 12.5% versus 14.3% and a relative risk (RR) of 0.89.
The difference in NDD diagnosis was largely explained by the diagnostic rates of AD (4.9 vs 6.0%, RR=0.82) and dementia (10.4 vs 11.8%, RR=0.88); by contrast, there was no significant association between HMT use and non-AD dementias, such as vascular dementia.
Noting that the analysis controlled for cerebrovascular and respiratory diseases, the authors suggest that there may be “a potential specific biological mechanism associated with estrogen loss in the brain in the pathophysiology of AD.” But they caution that the results may also be “due to a stronger association of cerebrovascular and respiratory disease with non-AD dementia.”
When patients were stratified by age, there was no significant difference in the risk for NDD or AD between women aged 65–69 years who did and did not receive HMT, whereas increasing age overall was associated with greater risk reduction for all NDDs in women taking HMT.
Further analysis indicated that tamoxifen (RR=0.84) and AIs (RR=0.83) were the HMTs associated with the greatest reductions in NDD.
Indeed, the researchers say that the impact of selective estrogen receptor modulators was “exclusively due to tamoxifen and not to raloxifene” and therefore may explain why earlier studies focused on raloxifene failed to show an association with AD.
While exemestane was associated with a greater reduction in the risk for AD or any dementia than anastrozole or letrozole, the team emphasizes that “both types of aromatase inhibitors exerted a protective association compared with patients with breast cancer who were not receiving any HMT.”
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JAMA Netw Open 2020; 3: e201541