ASPIRIN CAN REDUCE CANCER MORTALITY AND METASTASES RISK

Evidence from 3 new studies demonstrates that aspirin can reduce the risk for cancer-related mortality and can reduce or prevent the risk for distant metastasis.

Peter M. Rothwell, MD, PhD, professor of clinical neurology at the University of Oxford, United Kingdom, was lead author on all 3 studies.

In the first study, published online March 21 in the Lancet, comparing daily aspirin with no aspirin to prevent vascular events, aspirin use reduced the risk for nonvascular death in all 51 trials examined (1021 vs 1173 deaths; odds ratio [OR], 0.88; P = .003). When data from 34 trials were examined (n = 69,224; 89% of total cohort), there were fewer deaths from cancer in the aspirin than in the control group (562 vs 664 deaths; OR, 0.85; P = .008).

Dr. Rothwell and colleagues note that even though the decreased risk for major vascular events in these trials was initially offset by a higher risk for major bleeding, both of these effects diminished over time, leaving only the reduced risk for cancer after 3 years.

"In view of the very low rates of vascular events in recent and ongoing trials of aspirin in primary prevention, prevention of cancer could become the main justification for aspirin use in this setting," they write.

Compelling But No Recommendations Yet

In an accompanying editorial, Andrew T. Chan, MD, MPH, and Nancy R, Cook, ScD, both from Harvard Medical School in Boston, Massachusetts, note that although these results are compelling, they do have limitations.

These analyses exclude the largest randomized trials in primary prevention, the editorialists point out. The Women's Health Study (WHS) of 39,876 women treated with alternate-day aspirin 100 mg over 10 years and the Physicians' Health Study (PHS) of 22,071 men treated with alternate-day aspirin 325 mg over 5 years were not included in the current study because of possible differences in the biologic effect between alternate-day and daily aspirin intake. However, in these 2 studies, aspirin was not associated with a lower risk for colorectal cancer or overall cancer incidence or mortality.

Another limitation, say the editorialists, is that the researchers only used 6 randomized trials to analyze low-dose aspirin in the primary prevention of cancer.

In these 6 trials (n = 35,535), aspirin was shown to lower the incidence of cancer after 3 years in women (132 vs 176; OR, 0.75; P = .01), in men (192 vs 245; OR, 0.77; P = .008), and in both (324 vs 421; OR, 0.76; P = .0003).

A third limitation is that because the included studies were designed to examine cardiovascular end points, there was no information about cancer screening or surveillance.

Finally, some of the analyses were limited by the quality of available data; some estimates pooled individual-level data with published results.

But "caveats notwithstanding, Rothwell and colleagues show quite convincingly that aspirin seems to reduce cancer incidence and death across different subgroups and cancer sites, with an apparent delayed effect," they write. For most individuals, "the risk–benefit calculus of aspirin seems to favor aspirin's long-term anticancer benefit. These findings are consistent with observational findings and our understanding of the stepwise progression of carcinogenesis."

These data might not be the final word on aspirin, as far as making a population-based recommendation, the editorialists caution, because the WHS and PHS remain "significant counterbalancing trials that have not shown a cancer benefit with alternate-day aspirin up to 10 to 12 years."

Another factor to be considered is the adverse events from daily aspirin. Even though there is a "convincing case" that the vascular and anticancer benefits of aspirin outweigh the harms of major extracranial bleeding, less serious adverse effects on quality of life, such as less severe bleeding, are not accounted for in these analyses, Drs. Chan and Cook write.

Nonetheless, until data from forthcoming trials and longer-term follow-up from the WHS and PHS become available, this "impressive collection of data moves us another step closer to broadening recommendations for aspirin use," they conclude.

Metastasis in Randomized Trials

In the second study, also published online March 21 in the Lancet, Dr. Rothwell and colleagues analyzed data from 5 large randomized trials of daily aspirin (75 mg or more daily) for the prevention of vascular events in the United Kingdom. The cohort consisted of 17,285 trial participants, 987 of whom had a new solid cancer diagnosed during a mean follow-up of 6.5 years.

Aspirin use reduced the risk for cancer with distant metastasis (hazard ratio [HR] for all cancers, 0.64; P = .001). The risk for cancer with distant metastasis was reduced by 36%, and the risk for adencarcioma was reduced by 46% (P = .0007). Among patients with adenocarcinoma who did not have metastasis at their initial diagnosis and who remained on trial treatment up to or after diagnosis, the use of aspirin reduced the risk for metastasis on subsequent follow-up by about 70%.

Aspirin lowered the cancer mortality rate among patients who developed adenocarcinoma, especially in those without metastasis at diagnosis (HR, 0.50; P = .0006). Aspirin also lowered the overall risk for fatal adenocarcinoma (HR, 0.65; P = .0002), but not the risk for other fatal cancers (HR, 1.06; P = .64). These effects were independent of confounders such as age and sex, but the absolute benefit was greatest in smokers, the authors note.

Observation vs Randomized

The third study, published online March 21 in the Lancet Oncology, looked at the effect of aspirin on metastases, but with a different approach. The authors compared the effect of aspirin on the 20-year risk for cancer-specific mortality between observational studies and randomized trials.

They conducted this comparison because although randomized trials can clearly establish the risk for colorectal cancer, other solid tumors, and metastasis, such trials lack the statistical power to establish effects on less common cancers and on cancers in women.

Observational and case–control studies can provide these data if the results are shown to be reliable.

Overall, results from observational studies were similar to those from randomized trials, and showed that regular aspirin use lowered the long-term risk for several cancers and for distant metastasis.

In 6 eligible randomized trials, the aspirin group had a consistently lower 20-year risk for death from colorectal cancer than the control group (OR, 0.58; P = .0002). In the 26 case–control studies, any use of aspirin was associated with a lower risk for colorectal cancer (pooled OR, 0.67; P < .0001).

In 17 case–control studies, the regular use of aspirin was associated with a reduced risk for colorectal cancer (pooled OR, 0.62; P < .0001). In the randomized trials, there was good correlation between the effect of daily aspirin use and the 20-year risk for death from colorectal cancer (OR, 0.58; P = .0002).

The authors observed the same consistent reductions in risks for esophageal, gastric, biliary, and breast cancers, and estimates of the effect of aspirin on individual cancers in case–control studies were highly correlated with those seen in randomized trials (P = .0006). The largest effects were observed for gastrointestinal cancers.

In 5 studies, the regular use of aspirin was associated with a reduced proportion of cancers with distant metastasis (OR, 0.69; P < .0001); in 7 studies, it was not associated with a reduction in regional spread (OR, 0.98; P = .71). This was consistent with the findings from the randomized trials.

The authors note that "there is an urgent need for more data for effects on metastasis when aspirin is started after diagnosis of cancer."

More data are also needed for the effects of nonaspirin nonsteroidal anti-inflammatory drugs, they write, adding that "new case–control studies...have the potential to provide data quickly for each of these issues, with reasonable reliability and good statistical power."

All 3 studies were unfunded. Dr. Rothwell reports a financial relationship with several pharmaceutical companies with an interest in antiplatelet agents, including AstraZeneca, Bayer, Boehringer Ingelheim, sanofi-aventis, Bristol-Myers Squibb, and Servier; and being on the executive committee of the ARRIVE Trial. Coauthor F. Gerald R. Fowkes, FRCPE, from the Centre for Population Health Sciences, University of Edinburgh, United Kingdom, reports receiving research support and honoraria from AstraZeneca, Bayer, sanofi-aventis, and Bristol-Myers Squibb. Dr. Chan reports serving as a consultant to Bayer HealthCare and Millennium Pharmaceuticals. Dr. Cook reports being an investigator for the WHS.

NEW COLORECTAL CANCER SCREENING GUIDELINESS

A new American College of Physicians (ACP) guidance statement recommends individualized assessment of risk for colorectal cancer (CRC) in all adults. The new recommendations and an accompanying patient summary appear in the March 6 issue of the Annals of Internal Medicine.

"The [ACP] encourages adults to get screened for [CRC] starting at the age of 50," ACP President Virginia L. Hood, MBBS, MPH, FACP, said in a news release. "Only about 60 percent of American adults aged 50 and older get screened, even though the effectiveness of [CRC] screening in reducing deaths is supported by the available evidence."

In the United States, CRC is the second leading cause of cancer-related deaths for both men and women. The new ACP guidelines aim to educate physicians and patients regarding the benefits and harms of CRC screening, based on a review of current guidelines from other professional organizations.

A search of the National Guideline Clearinghouse revealed 4 guidelines meeting selection criteria: a joint guideline developed by the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology, and individual guidelines from the Institute for Clinical Systems Improvement, the US Preventive Services Task Force, and the American College of Radiology.

Specific ACP recommendations include the following:

1. Clinicians should perform individualized CRC risk evaluation in all adults. Risk factors for CRC incidence and mortality include older age; black race; personal history of polyps, inflammatory bowel disease, or CRC; and family history of CRC.
2. Clinicians should screen for CRC in adults at average risk beginning at 50 years of age, and in adults at high risk beginning at 40 years of age or at 10 years younger than the age at which the youngest affected relative was diagnosed with CRC. In these populations, the potential benefits of reduced mortality from earlier detection of CRC outweigh the potential harms of screening.
3. Patients at average risk may undergo CRC screening with a stool-based test, flexible sigmoidoscopy, or optical colonoscopy. Patients at high risk should undergo screening with optical colonoscopy. The benefits, harms, and availability of the specific screening test, as well as patient preferences, should affect choice of screening test. For adults older than 50 years who are at average risk, the recommended screening interval is 10 years for colonoscopy; 5 years for flexible sigmoidoscopy, virtual colonoscopy, and double contrast barium enema; and annually for fecal occult blood test.
4. Clinicians should stop CRC screening in adults older than 75 years or who have a life expectancy of less than 10 years because the potential harms of screening outweigh the potential benefits. Risks of colonoscopy include bleeding, intestinal perforation, and adverse reactions related to preparation for the procedure.

"We encourage patients to engage in shared decision making with their physician when selecting a [CRC] screening test so that they understand the benefits and harms," said Dr. Hood. "The success of any screening program, especially [CRC] screening, is dependent on the appropriate testing and follow-up of patients with abnormal screening results as well as following up with patients for repeat testing at designated intervals."

25 Easy Ways to Cut 100 Calories

Cut 100 calories and lose weight--without deprivation!

Cutting calories may seem like a daunting task, especially when you're trying to cut hundreds of calories each day to lose the recommended 1-2 pounds per week. Will you go hungry? Will your meals taste like cardboard? Will you have to give up your favorite foods?

Don't worry. When you make small changes, the only difference you'll notice is a drop in the scale! Keep in mind that cutting calories can involve smart substitutions or changes in portion sizes, too. Just remember, start small and work your way up to a new-and healthier-way of eating.

Beverages

1. Drink two 12-ounce light beers this weekend instead of two regular beers. Save 100 calories!

2. Eat a medium orange instead of drinking 12 ounces of fresh orange juice. Save 106 calories!

3. Enjoy 5 ounces of chocolate milk instead of 5 ounces of a chocolate milkshake. Save 110 calories!
Did you know that the protein in chocolate milk can help you ward off hunger? Get more Tips to Stay Full Longer

Breakfast

4. Spread your whole grain waffles with 2 tablespoons of maple syrup instead of 1 tablespoon of margarine or butter. Save 110 calories!

5. Try 1 ounce of maple turkey bacon instead of maple (pork) bacon. Save 118 calories!

6. Ditch the glazed donut and eat a bagel instead. Save 93 calories!

7. Grab a small bagel instead of a medium bagel. Save 99 calories!

8. Top your small bagel with 1.5 ounces of fat-free cream cheese in lieu of regular. Save 108 calories!

Dried fruit is a great way to curb sweet cravings, but it is higher in calories than fresh.

Snacks and Sides

9. Dip 1 cup celery into your favorite salsa or hummus instead of 1 ounce of tortilla chips. Save 125 calories!

10. Snack on 2 ounces pretzels instead of the same size portion of potato chips. Save 94 calories!

11. Bake 2 ounces of oven fries in lieu of 2 ounces of fast food fries. Save 88 calories!

12. Try 1.5 ounces of fresh grapes instead of 1.5 ounces of raisins. Save 98 calories!

13. Swap 1 cup of canned pineapple in heavy syrup for crushed pineapple in juice. Save 119 calories!
More easy ways to Cut Calories Without Dieting

Choose lean proteins like turkey instead of salty, fatty deli meats.
Lunch and Dinner

14. Build a sandwich with 1.5 ounces of deli turkey breast instead of an equivalent of hard salami.Save 119 calories!

15. Forget broccoli-cheddar soup. A 7- ounce portion of vegetable soup is better. Save 119 calories!

16. Enjoy 12 ounces of steamed rice (choose brown rice when possible) as an alternative to fried rice. Save 96 calories!

17. Unwrap your 13-inch tortilla wrap and make a sandwich on a 3-ounce whole grain bagel instead.Save 96 calories!
These swaps are a great way to kick-start a weight-loss plan. Learn How to Start Eating Healthier

Condiments and Sauces

18. Dip your salad in a side of ranch dressing (2 teaspoons) instead of pouring 2 tablespoons of dressing on the salad. Save 97 calories!

19. Skip the 5 ounces of Alfredo sauce and eat 7 ounces of marinara sauce. Save 129 calories!

20. Add flavor with 3 ounces of hot sauce-not 1 ounce of bleu cheese dressing. Save 117 calories!

21. Try either cheese or croutons on your salad-not both Save 72-116 calories!

Eat ice cream with a teaspoon in a small bowl, and a half-cup portion will feel like more.

Sweets and Desserts

22. Serve ice cream in a dish instead of a waffle cone. Save 121 calories!

23. Try a healthier peanut granola bar instead of a peanut candy bar. Save 94 calories!

24. Finish dinner with 1 cup of low-fat frozen yogurt instead of regular ice cream. Save 121 calories!

25. Substitute 5 ounces of apple pie with 5 ounces of baked apple crisp. Save 85 calories!

Cutting 100 calories here and there is an easy way to form healthier eating habits without feeling deprived or hungry. With just a few of these tricks up your sleeve, you'll be on your way to reaching your goals in no time!

LYNCH SYNDROME AND CANCER RISK

Mutations in genes that fix mismatched DNA have a well known association with colon and endometrial cancers, and now it appears they may also put people at extra risk for breast cancer and pancreatic cancer.

The mutations, known collectively as Lynch syndrome, "are very rare," according to Dr. Mark Jenkins, from the University of Melbourne. Researchers don't know exactly how common Lynch syndrome is, in part because people aren't generally tested unless they have a family history of colon or endometrial cancer.

Dr. Jenkins, senior author of a paper online Monday in the Journal of Clinical Oncology, said that at most one in 1,000 people probably has the condition.

Still, "the consequences for them are quite severe because the risks of cancer for them are quite high," Dr. Jenkins told Reuters Health.

His colleague Dr. Aung Ko Win led a team of researchers from Australia, New Zealand, Canada and the United States who followed 446 people with the gene mutations and 1,029 of their mutation-free relatives who were tested because someone in their family had colon or another cancer.

At the start of the study, none of the participants had been diagnosed with cancer themselves.

Among people with a family history of colon cancer, 4% of those with mismatch repair gene mutations were diagnosed with the disease during the next five years, compared to less than 0.5% of their mutation-free relatives.

Dr. Jenkins and his colleagues calculated that over five years, people with Lynch syndrome had 20 times the normal risk of colon cancer. Their risk was also 10-fold higher for pancreatic cancer, and four-fold higher for breast cancer.

People with the mutations also seemed to be at increased risk of endometrial, ovarian, stomach, bladder and kidney cancers.

In contrast, their relatives without the mutations didn't have an increased risk of any type of cancer, compared to expected rates of new diagnoses.

The link between Lynch syndrome and breast cancer in particular is still a controversial one, according to Dr. Albert de la Chapelle, a cancer geneticist from The Ohio State University in Columbus.

"It could be that there really is a slightly increased risk to get breast cancer," said Dr. de la Chapelle, who has worked with some of the authors before but wasn't involved in the new report.

But the conclusions, he said "are based on very small numbers," for example just 12 cases of breast cancer in mutation carriers and non-carriers combined.

Dr. Jinru Shia, from Memorial Sloan-Kettering Cancer Center in New York, told Reuters Health that the breast cancer result "goes along with our anecdotal experience" at her hospital.

The findings don't mean that everyone who tests positive for Lynch syndrome should get frequent screening for all cancers that were tied to the gene mutations, researchers agreed.

"Currently, screening is recommended for bowel cancer for people with this mutation, and we know that that screening works. For other cancers, there's less evidence that screening is effective," Dr. Jenkins said.

Meanwhile, Dr. Jenkins said the results are encouraging for the family members of people with Lynch syndrome who are themselves mutation-free and "don't need to worry" about any extra cancer risk.

That's been a concern because researchers have thought other genes, besides the four Lynch syndrome mutations, could be influencing cancer risks in those families.

"Now, one can say with confidence that those who turn out not to have the mutation, that their risk is the average risk," Dr. de la Chapelle told Reuters Health.

CANCER TREATMENT DURING PREGNANCY

Because cancer during pregnancy is a rare occurrence, with an incidence ranging from 0.02% to 0.10%, there is a scarcity of research to guide women and their physicians on treatment. Now, some experts have offered reassurance that it is possible to appropriately treat the mother without terminating the pregnancy.

Pregnancy should be preserved whenever possible with breast and gynecologic cancers, according to 2 separate review articles published in the February 11 issue of the Lancet. The most common malignancies diagnosed during pregnancy are gynecological (primarily uterine or cervical, and less frequently ovarian) and breast cancers; pregnancy does not have a deleterious effect on the prognosis of either.

Although prognosis and treatment success depends on the individual patient, it is possible to provide standard therapy to the mother while safeguarding the fetus.

Decisions about treatment for cancer in a pregnant woman can be difficult because of the conflict between the wellbeing of the mother and that of her unborn child, note Philippe Morice, MD, from the Institut Gustave Roussy, Villejuif, France, and colleagues in a comment accompanying the review papers.

They point out that the physician must define "when and how far to push back usual treatment limits to satisfy the patient's [ethical, legal, and/or personal beliefs]," but also must provide accurate information and consider the oncologic risks.

"The main goal is to offer pregnant patients the same optimum management (and therefore similar predicted survival) as nonpregnant patients," they write. Therefore, physicians must clearly define the real oncologic risk for each patient. Physicians need to stop thinking about cancer and pregnancy in general; instead, they need to focus on the particular cancer and its known characteristics.

Except for leukemia, true oncologic emergencies in pregnant women are rare, Dr. Morice and colleagues point out. This is fortunate because "time is required to deliberate and to draw up a personalized treatment plan that the patient will view as clear and balanced."

Treating cancer during pregnancy is still associated with unacceptable outcomes, such as the termination of pregnancies and the choice of an inadequate strategy for treatment of a tumor, they write.

"The treatment of every pregnant woman, and by extension every woman of childbearing age, should include a wider reflection on how to preserve the pregnancy or subsequent fertility, or both," Dr. Morice and colleagues explain. "Preservation of fertility in young women with cancer (an entirely new specialty, oncofertility) is every patient's right."

Pregnancy During Breast Cancer

In the review article on breast cancer during pregnancy, Frédéric Amant, MD, from the Multidisciplinary Breast Cancer Center, Leuven Cancer Institute, Katholieke Universiteit Leuven, Belgium, and colleagues note that a multidisciplinary focus and a cautious approach to radiotherapy are needed. A diagnostic strategy designed to reduce the burden of fetal radiation exposure needs to be established in a multidisciplinary setting.

Terminating the pregnancy does not improve the breast cancer prognosis, explained Dr. Amant. "We believe that fear of the toxic effects of chemotherapy should not be a reason for termination of pregnancy, and fear should not be a reason to delay maternal treatment or to induce prematurity," he told Medscape Medical News.

The therapeutic strategy should also be discussed within a multidisciplinary setting, and should adhere as closely as possible to standard protocols for nonpregnant women, say the authors, but fetal safety must also be considered.

Dr. Amant added that sometimes oncologists underestimate the long-term consequences of prematurity. "We believe children suffer more from prematurity than from antenatal exposure to chemotherapy," he said.

Until now, it was "easy to terminate pregnancy because the long-term effects were not known," said Dr. Amant. "With the current data, I believe it becomes unethical to terminate pregnancy when cancer is diagnosed."

A study recently published by Dr. Amant and colleagues showed that fetal exposure to chemotherapy was not associated with increased central nervous system, cardiac, or auditory morbidity. In addition, exposure did not appear to be associated with impairments to general health or growth, and cognitive development was age-adequate.

He added that if this trend is confirmed in more children with a longer follow-up, "I believe termination will be more difficult to defend."

In their review paper, Dr. Amant and colleagues explain that surgery, chemotherapy, and radiotherapy for breast cancer are possible during pregnancy, with the caveat that treatment should be tailored to the individual patient.

Generally, surgery can be conducted safely during any stage of pregnancy and most anesthetic agents seem to be safe for the fetus, they point out. The choice of surgery should follow the same guidelines as those for nonpregnant women, and radiation therapy after a breast-conservation procedure is rarely a concern; most women receive chemotherapy and delay radiotherapy until after delivery.

After the first trimester of pregnancy, chemotherapy can be either adjuvant or neoadjuvant, and the decision to use chemotherapy should follow the same guidelines as for nonpregnant women, the authors report. The goal should also be a term delivery (37 weeks or more), and premature birth should be avoided if possible.

Cervical and Ovarian Cancers During Pregnancy

In the review paper on gynecologic cancers, Dr. Morice and his colleagues from France and the United States focused on the 2 most common and complex gynecologic cancers — cervical and ovarian. As in breast cancer, a multidisciplinary discussion is essential for optimal disease management, note the authors. Physicians need to consider the possibility of saving the fetus and the effect of therapy on the woman's reproductive capacity.

Dr. Morice and colleagues point out that until the 1980s, cervical cancer diagnosed during the first 2 trimesters was managed by ending the pregnancy and radically treating the cervical neoplasm. The current trend is to try to preserve the pregnancy, especially in patients with early-stage disease with no nodal involvement.

The management of cervical cancer depends largely on 4 criteria: the extent of local spread, nodal status, pregnancy trimester, and histologic subtype. The authors explain that in early-stage cervical cancer, during the first and at the beginning of the second trimester, magnetic resonance imaging and laparoscopic lymphadenectomy can be used to help plan a conservative approach.

Among women with small tumors and without nodal spread, postponing treatment until fetal maturity and delivery can be discussed. In these cases, radical trachelectomy and neoadjuvant chemotherapy might be appropriate.

The treatment of patients with locally advanced disease is controversial — neoadjuvant chemotherapy with preservation of the pregnancy or chemotherapy and radiotherapy — and needs to be discussed on a case-by-case basis. Tumor size, radiologic findings, the term of pregnancy, and the patient's wishes must be taken into consideration, the authors note.

The management of ovarian cancer is dependent on histologic type, stage, and pregnancy trimester. In patients with peritoneal spread or high-risk early-stage disease, preservation of the pregnancy might be possible with neoadjuvant chemotherapy, according to Dr. Morice and colleagues.

Chemotherapy is generally necessary to achieve a cure in ovarian cancer, and the risk for a congenital malformation or miscarriage as a consequence is very high during the first trimester. In such cases, "consideration of a therapeutic abortion versus delayed treatment should be discussed with the patient," they write. However, treatment during subsequent trimesters can be given according to the usual standard chemotherapy guidelines for both germ-cell tumors and epithelial ovarian cancer; in most cases, there are generally no irreversible consequences for the fetus.

It is also usually not necessary to induce premature delivery if the cancer is controlled with chemotherapy.

"Clinical studies are needed, particularly for key issues in clinical management, such as an intentional delay in early-stage cervical cancer or radical trachelectomy and neoadjuvant chemotherapy, to establish the balance between the best chance of cure for the patient and preservation of a healthy fetus," Dr. Morice and colleagues emphasize.

Nefertiti duPont, MD, MPH, who was approached by Medscape Medical News for an independent comment, noted that this is "an excellent review of a difficult topic."

"When diagnosed early, gynecologic cancers in pregnancy can lead to good outcomes for the mother and infant," said Dr. duPont, who is assistant professor and director of the High Risk Ovarian Cancer Screening Clinic, Roswell Park Cancer Institute, Buffalo, New York. "The most important issues are close follow-up of the mother during her pregnancy and postpartum course, and long-term follow-up of the infant."

What is also critical is a multidisciplinary team to ensure that the mother and baby have the best possible outcomes, she explained.

Several areas in the review, however, could be strengthened, Dr. duPont noted. "Clinicians should provide psychosocial and emotional support to the mother during diagnosis and treatment," she said. "Also, most studies recommend postponing chemotherapy within 3 weeks of delivery to avoid neonatal myelosuppression."