Health Benefits of Aspirin: Breast, Ovarian and Cervical Cancer

Aspirin use lowers breast & ovarian cancer risk

Postmenopausal women who regularly use aspirin and other analgesics (known as painkillers) have lower estrogen levels, which could contribute to a decreased risk of breast or ovarian cancer.

"We observed some significant inverse associations between concentrations of several estrogens and the use of aspirin, aspirin plus non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and all analgesics combined," said Margaret A. Gates, Sc.D., research fellow at the Channing Laboratory at Brigham and Women's Hospital and Harvard Medical School.

"Our results suggest that among postmenopausal women, regular users of aspirin and other analgesics may have lower estrogen levels than non-users," Gates added.

These study results are published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.

Gates and colleagues examined the association between use of aspirin, NSAIDs and acetaminophen and concentrations of estrogens and androgens among 740 postmenopausal women who participated in the Nurses' Health Study.

Frequency of all analgesic use was inversely associated with estradiol, free estradiol, estrone sulfate and the ratio of estradiol to testosterone.

Average estradiol levels were 10.5 percent lower among women who regularly used aspirin or non-aspirin NSAIDs. Similarly, free estradiol levels were 10.6 percent lower and estrone sulfate levels were 11.1 percent lower among regular users of aspirin or other NSAIDs. Among regular users of any analgesic (aspirin, NSAIDs or acetaminophen), levels of these hormones were 15.2 percent, 12.9 percent and 12.6 percent lower, respectively, according to Gates.

Michael J. Thun, M.D., M.S., vice president emeritus of epidemiology and surveillance research at the American Cancer Society, said the question of whether regular use of aspirin and other NSAIDs is causally related to reduced breast cancer risk is important, but still unresolved.

Thun believes these study results do not confirm whether aspirin-like drugs caused the reduction in circulating estradiol. However, the results do provide evidence that aspirin and other NSAIDs might reduce circulating levels of estradiol by about 10 percent, according to Thun, who is an editorial board member of Cancer Epidemiology, Biomarkers & Prevention, and was not associated with this study.

"Hopefully these findings will motivate a trial to determine whether the association between aspirin use and hormone levels is causal," he said. "Until then, we have a possible mechanism for a potentially important, but as yet unproven chemopreventive benefit."

Gates agreed and said that additional research, like a randomized trial of NSAID use and hormone levels, is needed to confirm these results and to determine whether the decrease in hormone levels translates to a reduced risk of breast or ovarian cancer. If an inverse association between analgesic use and risk of breast or ovarian cancer is confirmed, then this research may have important public health implications.

"Although the overall risks and benefits would need to be weighed, analgesics could be implemented as a chemopreventive and may decrease the risk of several cancers," she said.

Breast Cancer Patients Who Take Aspirin Reduced Risk of Metastasis and Death by Half

An analysis of data from the Nurse’s Health Study, a large, ongoing prospective observational study, shows that women who have completed treatment for early-stage breast cancer and who take aspirin have a nearly 50 percent reduced risk of breast cancer death and a similar reduction in the risk of metastasis.

“This is the first study to find that aspirin can significantly reduce the risk of cancer spread and death for women who have been treated for early-stage breast cancer, " said Michelle Holmes, MD, DrPH, associate professor of medicine and epidemiology at Harvard Medical School & Harvard School of Public Health and the study's lead author. “If these findings are confirmed in other clinical trials, taking aspirin may become another simple, low-cost and relatively safe tool to help women with breast cancer live longer, healthier lives."

Investigators report it is not yet clear how aspirin affects cancer cells, but they speculate it decreases the risk of cancer metastasis by reducing inflammation, which is closely associated with cancer development. Prior studies have also suggested that aspirin inhibits cancer spread: one study found that people with colon cancer who took aspirin lived longer than those who did not, and laboratory studies have also shown that aspirin inhibited the growth and invasiveness of breast cancer cells.

In this analysis, researchers evaluated data from the Nurses' Health Study, which included 4,164 female nurses in the United States (ages 30 to 55 in 1976) who were diagnosed with stage I, II, or III breast cancer between 1976 and 2002 and were followed through June 2006. They examined patients’ use of aspirin for one or more years after a breast cancer diagnosis (when patients would have completed treatment such as surgery, radiation therapy, and/or chemotherapy) and the frequency of metastasis and breast cancer death. (The authors emphasized that patients undergoing active treatment should not take aspirin due to potential interactions that can increase certain side effects.)

A total of 400 women experienced metastasis, and 341 of these died of breast cancer. Women who took aspirin two to five days per week had a 60 percent reduced risk of metastasis and a 71 percent lower risk of breast cancer death. Those who took aspirin six or seven days a week had a 43 percent reduced risk of metastasis and a 64 percent lower risk of breast cancer death. The risk of breast cancer metastasis and mortality did not differ between women who did not take aspirin and those who took aspirin once a week.

Researchers also found that women who took non-aspirin non-steroidal inflammatory drugs (NSAIDs) six or seven days a week also had a reduced risk of breast cancer death (a 48 percent reduction), but women who took NSAIDS less frequently and those who used acetaminophen did not experience such a benefit.

While the investigators did not collect data on aspirin dose, they noted that women who took aspirin regularly most likely took it for heart disease prevention; the typical dose for that purpose is 81 mg/day.

Aspirin may reduce risk of breast cancer

Taking aspirin on a daily basis may lower women’s risk of a particular type of breast cancer, according to results published in BioMed Central’s open access journal Breast Cancer Research. In this large study, aspirin use was linked to a small reduction in estrogen receptor-positive breast cancers. However, unlike in some previous research, aspirin and related painkillers were not found to reduce the total risk of breast cancer.

Around 75% of breast cancers are estrogen receptor-positive (ER+), which means the cancer cells have receptors for the female hormone estrogen on their surface. Estrogen helps the cancer cells grow, so drugs that block the action of estrogen are often used to treat ER+ cancer.

It is feasible, in theory, that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) could lower the total risk of breast cancer. They block an enzyme called cyclooxygenase, an activity that could disrupt breast cancer development in a number of ways – for example, by reducing the amount of estrogen produced in the body.

A US research team, led by Gretchen Gierach, studied over 127,000 women enrolled in the National Institutes of Health–AARP Diet and Health Study, which was designed to explore the possible links between diet, health-related behaviours and cancer in older people in the USA. For the current research, the participants were women aged 51–72 with no history of cancer.

Unlike other NSAIDs, aspirin has irreversible effects on cyclooxygenase (COX) enzymes, so the study authors looked for differences in cancer development according to whether women used aspirin or another kind of NSAID.

NSAID use was not linked to total risk of breast cancer in this study. However, when the team considered different cancer subtypes and specific types of NSAIDs, they found that daily aspirin use was associated with a small reduction (16%) in the risk of ER+ breast cancer. A similar link was not seen in cases of ER- breast cancer.

Gierach concludes: “In summary, our results do not support an important influence of NSAIDs on total breast cancer risk. Daily aspirin use, however, appeared to offer some protection for ER+ breast cancer in this population. Our results provide support for further evaluating relationships in prospective studies with well-defined measures of NSAID use by NSAID type and by ER status.”

Regular use of low-dose aspirin may prevent the progression of breast cancer

Regular use of low-dose aspirin may prevent the progression of breast cancer, according to results of a study by researchers at the Veterans Affairs Medical Center in Kansas City, Mo., and the University of Kansas Medical Center.

The study found that aspirin slowed the growth of breast cancer cell lines in the lab and significantly reduced the growth of tumors in mice. The age-old headache remedy also exhibits the ability to prevent tumor cells from spreading.

The lead author of the study, Gargi Maity, a postdoctoral fellow who works in the cancer research unit at the VA Medical Center, presented the team's findings on at the annual meeting of the American Society for Biochemistry and Molecular Biology, which was held in conjunction with the Experimental Biology 2013 conference in Boston. The senior author is Sushanta Banerjee, director of the cancer research unit and a professor at the University of Kansas Medical Center in Kansas City, Kan.

The role of aspirin, or acetylsalicylic acid, in preventing and treating cancer has intrigued researchers since the late 1980s, when an Australian study found that people who regularly used aspirin were less likely to develop colorectal cancer. Aspirin use also has been shown to reduce the risk of squamous cell esophageal cancer and prostate cancer.

Anecdotal evidence indicated that breast cancer was less likely to return in women who took aspirin to lower their risk of heart attack or stroke. But the science behind this relationship is not well understood.

The VA study found that aspirin may interfere with cancer cells' ability to find an aggressive, more primordial state. In the mouse model the researchers used, cancer cells treated with aspirin formed no or only partial stem cells, which are believed to fuel the growth and spread of tumors.

Banerjee, a professor of medicine in division of hematology and oncology, says first-line chemotherapy treatments do not destroy stem cells. Eventually, the tumor will grow again. "If you don't target the stemness, it is known you will not get any effect," he says. "It will relapse."

In lab tests, aspirin blocked the proliferation of two different breast cancer lines. One of the lines tested is often called triple-negative breast cancer, a less common but more difficult treat form of the disease. "We are mainly interested in triple negative breast cancer, because the prognosis is very poor," Banerjee says.

Triple-negative breast cancers, which will be addressed in a special thematic program at the ASBMB annual meeting, lack receptors for estrogen, progesterone and Her2. Aspirin also may improve the effectiveness of current treatments for women whose breast cancers are hormone-receptor positive. In the team's study, aspirin enhanced the effect of tamoxifen, the usual drug therapy for hormone-receptor positive breast cancer.

Aspirin is used in the treatment of a number of different conditions. Banerjee says its ability to attack multiple metabolic pathways is what makes it potentially useful in the fight against cancer. "Cancer is not a single-gene disease," he says. "Multiple genes are involved."

Aspirin is a medicine with side effects, including gastrointestinal bleeding. Researchers will continue to explore if the positive effects of regular use of the drug outweigh the risks. In 2012, the National Cancer Institute asked scientists to design studies that would illuminate the mechanisms by which aspirin and drugs with other uses appear to reduce the risk of cancer or improve the prognosis for those diagnosed with the disease. Banerjee says his lab will apply for one of the grants.

Aspirin may slow recurrence in breast cancer patients

New findings published today in the journal Cancer Research reveal that some postmenopausal overweight breast cancer patients who use common anti-inflammatory drugs like aspirin or ibuprofen have significantly lower breast cancer recurrence rates.

Researchers from the Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio and the University of Texas at Austin began by examining blood serum from CTRC breast cancer patients, said CTRC oncologist Andrew Brenner, M.D., Ph.D.

Studying Blood Serum

They placed the serum in a culture of fat cells that make estrogen, and then placed the serum on breast cancer cells. The serum from overweight and obese patients caused the cancer cells to grow much more aggressively than the serum from patients who were not overweight.

"It looks like the mechanism is prostaglandins, which have a role in inflammation, and there's more of it in the obese patient serum," Dr. Brenner said.

Based on those findings, the researchers did a retrospective study on patients from the CTRC and the START Center for Cancer Care. They were segregated into those taking COX2 inhibitors (aspirin or ibuprofen) and those who did not.

Finding a Lower Recurrence Rate

"Patients who were on COX2 inhibitors tended to have a lower recurrence rate," Dr. Brenner said.

Anti-inflammatory use reduced the recurrence rate of ERα positive breast cancer by 50 percent and extended patients' disease-free period by more than two years. ER positive breast cancers, cancers that grow in response to exposure to the hormone estrogen, are among the most common form of the disease, accounting for approximately 75 percent of diagnoses.

Cancer researcher Linda deGraffenried, Ph.D., from The University of Texas at Austin, designed the study, working closely with Dr. Brenner and Murali Beeram, M.D., a cancer specialist from the START Center.

The investigators caution that these results are preliminary.

"Overweight or obese women diagnosed with breast cancer are facing a worse prognosis than normal-weight women," said Dr. deGraffenried, who is also adjunct assistant professor in the Department of Cellular and Structural Biology at the Health Science Center.

Facing a Different Disease

"We believe that obese women are facing a different disease. There are changes at the molecular level. We want to reduce the disease-promoting effects of obesity." Based on those results, the CTRC has launched a pilot anti-inflammatory trial in a joint venture with UT Austin, and the research partners are seeking funding for a larger study.

"We would like to identify which women are most likely to benefit from interventions like adding NSAIDs to treatment regimens," Dr. deGraffenried said.

Aspirin works to reduce breast cancer deaths by preventing the cancer spreading to nearby lymph nodes

Researchers have discovered that women who had been prescribed aspirin regularly before being diagnosed with breast cancer are less likely to have cancer that spread to the lymph-nodes than women who were not on prescription aspirin. These women are also less likely to die from their breast cancer.

The study of Irish patients funded by the Irish Health Research Board and Irish Cancer Society and published by the American Association for Cancer Research in the Journal, Cancer Research, analyses records from the National Cancer Registry Ireland (NCRI), and prescription data from the General Medical Service (GMS) pharmacy claims database.

"Our findings suggest that aspirin could play a role in reducing mortality from breast cancer by preventing the cancer spreading to nearby lymph nodes", said Dr Ian Barron, the lead author who carried out the research at Trinity College Dublin, and is now working at Johns Hopkins, USA.

"We analysed data from 2,796 women with stage I-III breast cancer. We found that those women prescribed aspirin in the years immediately prior to their breast cancer diagnosis were statistically significantly less likely to present with a lymph node-positive* breast cancer than non-users. The association was strongest among women prescribed aspirin regularly and women prescribed higher aspirin doses. We now need to establish how and why this is the case".

The findings are consistent with two other major studies. The first is an analysis of cardiovascular trials where pre-diagnostic aspirin** use was associated with a statistically significant reduction in the risk of developing metastases and dying from cancer.

The second is an observation from in vivo breast cancer models, which suggest a possible mechanism by which aspirin may reduce the risk of cancer spreading to other parts of the body. 
 

Aspirin May Reduce Ovarian Cancer Risk

Women who take aspirin daily may reduce their risk of ovarian cancer by 20 percent, according to a study by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health. However, further research is needed before clinical recommendations can be made.

The study was published Feb. 6, 2014, in the Journal of the National Cancer Institute.

It is estimated that over 20,000 women in the United States will be diagnosed with ovarian cancer in 2014, and more than 14,000 will die from the disease. Early stage ovarian cancer may be successfully treated. However, symptoms associated with this disease can mimic more common conditions, such as digestive and bladder disorders, so for this reason and others, it is often not diagnosed until it has reached advanced stages. Late stage ovarian cancer leaves women with limited treatment options and poor prognoses, making preventive strategies potentially important for controlling this disease.

Chronic or persistent inflammation has been shown to increase the risk of cancer and other diseases. Previous studies have suggested that the anti-inflammatory properties of aspirin and non-aspirin NSAIDs (non-steroidal anti-inflammatory drugs), may reduce cancer risk overall. However, studies examining whether use of these agents may influence ovarian cancer risk have been largely inconclusive.

This is the largest study to date to assess the relationship between these drugs and ovarian cancer risk.

Britton Trabert, Ph.D., and Nicolas Wentzensen, M.D., Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics, and their colleagues, analyzed data pooled from 12 large epidemiological studies to investigate whether women who used aspirin, non-aspirin NSAIDs, or acetaminophen have a lower risk of ovarian cancer. These 12 studies (nine from the United States) were part of the Ovarian Cancer Association Consortium. The scientists evaluated the benefit of these drugs in nearly 8,000 women with ovarian cancer and close to 12,000 women who did not have the disease.

Among study participants who reported whether or not they used aspirin regularly: 18 percent used aspirin, 24 percent used non-aspirin NSAIDs, and 16 percent used acetaminophen. The researchers determined that participants who reported daily aspirin use had a 20 percent lower risk of ovarian cancer than those who used aspirin less than once per week.

For non-aspirin NSAIDs, which include a wide variety of drugs, the picture was less clear: the scientists observed a 10 percent lower ovarian cancer risk among women who used NSAIDs at least once per week compared with those who used NSAIDs less frequently. However, this finding did not fall in a range that was significant statistically.

In contrast to the findings for aspirin and NSAIDs, use of acetaminophen, which is not an anti-inflammatory agent, was not associated with reduced ovarian cancer risk.

The results were reported in the February 2014 issue of the Journal of the National Cancer Institute.

This study adds to a growing list of malignancies, such as colorectal and other cancers, that appear to be potentially preventable by aspirin usage. “Our study suggests that aspirin regimens, proven to protect against heart attack, may reduce the risk of ovarian cancer as well. However intriguing our results are, they should not influence current clinical practice. 

Aspirin may decrease risk of aggressive form of ovarian cancer

New research shows that women who regularly use pain relief medications, particularly aspirin, have a decreased risk of serous ovarian cancer—an aggressive carcinoma affecting the surface of the ovary. The study published (October, 2012) in Acta Obstetricia et Gynecologica Scandinavica, a journal of the Nordic Federation of Societies of Obstetrics and Gynecology, reports that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), or other analgesics did not decrease ovarian cancer risk.

Ovarian cancer is the deadliest gynecological malignancy and the fifth-leading cause of death by cancer for women in developed countries. Previous studies report that Denmark has one of the highest incidence and mortality rates at 11 and 7 per 100,000 women, respectively. According to the Centers for Disease Control and Prevention (CDC), each year 20,000 women in the U.S. are diagnosed with ovarian cancer, with 90% of cases occurring in women older than 40 years of age and the greatest number in those 60 years or older.

"Ovarian cancer has a high mortality. Understanding what factors are involved in the development of this disease and investigating preventative interventions for women are vitally important," said lead author Dr. Susanne Kjær with the Danish Cancer Society Research Center. "Our study examined the role of analgesics in development of ovarian cancer."

For the present study, researchers used data from the malignant ovarian cancer (MALOVA) study, a population-based, case-control study investigating this cancer in Danish women between 1995 and 1999.

The team analyzed data from 756 women with epithelial ovarian cancer, classified by type of glandular tumors (adenocarcinomas); 447 were serous, 138 were mucinous, and 171 were other types. A random sample of 1564 women between the ages of 35 and 79 were drawn from the general population as controls. Personal interviews were conducted to determine analgesic drug use.

Findings indicate that women taking aspirin on a regular basis decreased their risk of serous ovarian cancer (odds ratio, OR=.60). Researchers did not find a decrease in ovarian cancer risk in women who regularly used non-aspirin NSAIDs, acetaminophen, or other types of pain relievers.

Dr. Kjær concludes, "Our findings suggest a potential protective effect of analgesic use on ovarian cancer risk, but that benefit should be balanced against adverse effects of pain medication use, such as risk of bleeding and peptic ulcers." The authors recommend that larger studies, which accurately assess dosage, frequency and duration of pain medications, are necessary to understand the impact of analgesic use on ovarian cancer.

In his editorial, also published in this month's issue, Dr. Magnus Westgren from Karolinska University Hospital in Stockholm, Sweden concurs with the study authors that strategies for preventing ovarian cancer are imperative. 

Frequent aspirin use reduces risk of cervical cancer by nearly half

Long-term and frequent use of aspirin is associated with significantly decreased risk of cervical cancer, according to a study led by researchers at Roswell Park Cancer Institute (RPCI) and published in the Journal of Lower Genital Tract Disease.

Aspirin use was associated with a 47% reduced risk of cervical cancer among frequent users -- those who used aspirin seven or more times a week, regardless of duration -- and 41% reduced risk among long-term frequent users -- those with five or more years of frequent use. Acetaminophen use was not associated with decreased risk of cervical cancer. A research team led by Kirsten Moysich, PhD, Professor of Oncology in the Department of Cancer Prevention and Control at Roswell Park, reported the results from the first U.S.-based study to examine the association between regular use of aspirin or acetaminophen.

"Aspirin use remains an attractive cancer-prevention option, due to the fact that most people will be more likely to take a pill rather than make major lifestyle modifications such as quitting smoking, eating a healthy diet and engaging in physical activity. However, people need to talk to their doctor before starting an aspirin regimen," says Dr. Moysich.

The study examined 328 patients with cervical cancer and 1,312 controls, matched on age and decade, who enrolled in a hospital-based case-control study drawn from 26,831 patients who received treatment at Roswell Park Cancer Institute and completed the Patient Epidemiology Data System questionnaire between 1982 and 1998. Participants provided self-reported information on the frequency and duration of aspirin and/or acetaminophen use.

"Further research is needed," adds Dr. Moysich, "on the role of daily, long-term use of aspirin and acetaminophen as both cervical cancer chemopreventive agents and enhancement to standard treatment strategies post-diagnosis."

According to the American Cancer Society, 12,900 new cases of cervical cancer will be diagnosed and 4,100 women will die from the disease in 2015.