MRI of Little Benefit to Most Women With Breast Cancer

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November 24, 2011 — For the majority of women with breast cancer, there is no evidence that magnetic resonance imaging (MRI) improves outcome, according to a study published in the November 19 issue of the Lancet.

There is limited evidence that screening women for breast cancer with MRI is beneficial or that its routine use before breast-conserving surgery improves patient selection, reduces surgical procedures, or lowers the risk for local cancer recurrences, say the researchers.

However, MRI screening is of benefit in women at genetically high risk, lead author Monica Morrow, MD, who is chief of the breast service and professor of surgery at the Memorial Sloan-Kettering Cancer Center in New York City, told Medscape Medical News.

It is also better than other methods for assessing response to neoadjuvant chemotherapy and identifying the primary tumor in patients who present with axillary adenopathy, Dr. Morrow said.

"For very high-risk women — that is those who have BRCA mutations or a family history suggestive of such mutations — I think there is good evidence that MRI screening is an advantage, but that's a very small population of women," Dr. Morrow told Medscape Medical News.

"In patients with breast cancer, the use of MRI has become very common in the United States. When it started a number of years ago, people made the assumption that finding more cancers, which MRI does, is bound to benefit patients," Dr. Morrow said.

"Now we have actual outcome data that look at whether or not that assumption is true, and the amount of outcome data has been increasing over time. It seemed like a good time to put that together and review it, along with the evidence from trials of screening," she said.

In this review, which represents the first paper in the Lancet series on breast cancer, Dr. Morrow and her team conducted an electronic literature search of articles published from May 1, 2001 to May 25, 2011 in PubMed, Embase, and Cochrane.

The strongest evidence of benefit for the use of MRI as a screening tool was found in women with BRCA mutations and in women with a family history of breast cancer. MRI has better sensitivity than mammography for the detection of invasive breast cancer, which results in the detection of smaller cancers and the occurrence of fewer interval cancers.

However, none of the prospective randomized trials of breast cancer screening with MRI — either in women in general or in women at high risk — had survival as an end point. So whether the benefits seen translate into a survival advantage is still unknown, Dr. Morrow explained.

MRI for Surgical Planning

 

The researchers also found little evidence that MRI improves the short-term or long-term outcomes of breast-conserving surgery.

They cite 2 randomized trials — MONET (Eur J Cancer. 2011;47:879-886) and COMICE (Lancet. 2010;375:563-571) — that showed that screening patients with MRI did not lead to any decrease in surgical procedures.

Radiologist Stamatia Destounis, MD, from the University of Rochester Medical Center in New York, who was approached for comment by Medscape Medical News, said that the surgeons at her hospital find MRI very helpful for surgical planning.

Dr. Destounis explained that MRI has enabled clinicians to find incidental contralateral cancers. She cited a study demonstrating that MRI can detect cancer in the contralateral breast that is missed by mammography at the time of the initial breast cancer diagnosis (N Engl J Med. 2007;356:1295-1303).

"Dr. Morrow said that there have been no studies that found MRI helpful for contralateral breast cancer diagnosis at the time when one side is diagnosed, but we in radiology do have those articles. We are growing our MRI practice because we find that this is a very helpful tool," she said.

Dr. Destounis agrees that long-term outcome results with MRI are lacking.

"This is true. We don't have randomized trials that follow, long-term, what happens to the patient who gets MRI prior to surgery and the patient who does not.... But I think that people are working on the premise — and this is the premise that all radiologists work from — that if we identify something as early as possible, then the outcome will be better because the disease is small enough to be treated with surgery. It's not invasive. It's not metastatic. That is our premise."

By: Fran Lowry

Coffee Linked to Lower Endometrial Cancer Risk

November 22, 2011 — Drinking at least 4 cups of coffee per day is associated with a lower risk for endometrial cancer, according to new data from the Nurses' Health Study.

Youjin Je, a doctoral candidate in the lab of Edward Giovannucci, MD, ScD, from the Department of Nutrition and Epidemiology at the Harvard School of Public Health in Boston, Massachusetts, and colleagues published their findings online November 22 in Cancer Epidemiology, Biomarkers & Prevention.

"Coffee consumption may be related to endometrial cancer development due to the potential role of caffeine," Dr. Giovannucci and colleagues write. "Several epidemiologic studies have reported an inverse association between coffee intake and endometrial cancer risk, but data from prospective studies are limited."

Therefore, the researchers prospectively examined the link between drinking coffee and endometrial cancer risk, using prospective data from the Nurses' Health Study.

The analysis included data from 67,470 women aged 34 to 59 years in 1980. Cumulative average coffee intake was determined by questionnaire. During 26 years of follow-up, researchers documented 672 cases of endometrial cancer.

However, drinking 4 or more cups of coffee per day was associated with a 25% relative risk reduction compared with consuming less than 1 cup daily (multivariable rate ratio, 0.75; 95% confidence interval [CI], 0.57 - 0.97; P _trend = .02). Drinking between 2 and 3 cups of coffee per day was linked with a 7% reduced risk, but the difference did not reach statistical significance (rate ratio, 0.93; 95% CI, 0.76 - 1.14; P _trend = .02).

In terms of absolute risk reduction, women who drank 4 or more cups of coffee reduced their risk for endometrial cancer from 56 cases per 100,000 women to 35 cases per 100,000 women. The investigators saw a similar association when they restricted their analysis to caffeinated coffee consumption. In that case, there was a 30% relative risk reduction in endometrial cancer risk associated with consumption of 4 or more cups compared with less than 1 cup a day.

For decaffeinated coffee consumption, drinking 2 or more cups per day was linked with a 22% relative reduction in risk for endometrial cancer vs drinking less than 1 cup per month, but the difference did not reach statistical significance, perhaps because of the smaller cohort size (relative risk, 0.78; 95% CI, 0.57 - 1.08; P _trend = .58). The researchers saw no association between tea drinking and endometrial cancer risk.

In subgroup analyses, there was a stronger inverse association with high coffee intake among obese women. "Because obese women tend to have insulin resistance, oxidative stress, and relatively low levels of [sex hormone binding globulin], the potential abilities of coffee to improve those conditions may have contributed to a decreased risk of endometrial cancer among obese women," the authors write.

"Coffee has already been shown to be protective against diabetes due to its effect on insulin," noted Dr. Giovannucci in a written release. "So we hypothesized that we'd see a reduction in some cancers as well." According to Dr. Giovannucci, laboratory testing has found that coffee has many more antioxidants than most vegetables and fruits.

By: Emma Hitt, PhD

Does Liposuction Offer More Than a Cosmetic Benefit?

September 30, 2011 (Denver, Colorado) — Patients who receive liposuction or liposuction with abdominoplasty might emerge from those procedures with metabolic profiles less attuned to cardiovascular disease and other complications, a recent study of 322 individuals who presented with a range of body mass indices has found.

According to Eric Swanson, MD, a plastic surgeon in Leawood, Kansas, decreases in circulating triglyceride levels and leukocyte counts in both men and women after fat-reduction surgery have a beneficial impact on the reduction of systemic inflammatory status, and might illuminate the role of subcutaneous fat relative to visceral fat in disease mechanisms and type 2 diabetes.

Dr. Swanson presented data from his prospective study here at Plastic Surgery 2011: American Society of Plastic Surgeons Annual Meeting.

"Patients with normal triglyceride levels experienced no significant change after liposuction," he told Medscape Medical News. "However, patients with levels of greater than 150 mg/dL demonstrated a 43% reduction. In fact, 62% of these patients whose levels were at risk before liposuction had normal levels after liposuction."

Triglyceride levels above 150 mg/dL have been associated with an elevated risk for metabolic syndrome, type 2 diabetes, stroke, coronary artery disease, and peripheral vascular disease.

"We do know that the drop in triglyceride levels we found in these patients actually exceeded what can be accomplished medically," Dr. Swanson explained, "so it may be that there is a therapeutic benefit."

Dr. Swanson and colleagues reviewed data from 270 women and 52 men who scheduled fat-reduction procedures over a 2-year period; 22% were considered obese. In the study, 229 underwent superwet ultrasonic liposuction alone and 89 underwent liposuction combined with abdominoplasty. Among the women, 65% underwent lower-body procedures; among the men, 85% underwent trunk fat procedures. Fasting blood tests were performed preoperatively, and at 1 and 3 months postoperatively.

Among the patients undergoing liposuction alone, mean triglyceride levels decreased 26% (P < .05). Of this group, 37% presented with elevated triglyceride levels prior to surgery; that proportion dropped to 18% after the procedure (P < .001).

Patients who underwent liposuction with abdominoplasty experienced reductions that were less dramatic.

Dr. Swanson asserted that this evidence throws light on discussions concerning the metabolic role of fat under the skin, in comparison to the fat that surrounds internal organs.

"A 2004 study published in the New England Journal of Medicine found no difference in lipid levels after liposuction [N Engl J Med. 2004;350:2549-2557]. But that study was limited by the fact that there were only 15 patients — all obese females and all treated in the abdomen only," he said.

"My study found that there is a substantial reduction in triglyceride levels, probably because not all patients were obese. Thus, the fat reduction relative to total body fat was proportionately greater. For decades, the medical community has viewed visceral fat as more harmful than subcutaneous fat. Many studies have challenged this traditional concept. My study suggests that subcutaneous fat is just as important metabolically as visceral fat."

The findings suggest a need for additional research to quantify the true contribution of subcutaneous fat to various disease etiologies, he said.

Al Aly, MD, professor of surgery at the University of California in Irvine, who was not involved in the research, agreed that the question carries a fair amount of clinical significance.

"Visceral fat has function. You can't just go in there willy nilly and cut out visceral fat," he explained. "We need to leave that alone. I don't think that with this scientific paper we can say noncentral (subcutaneous) fat is more important. All you can say is that it may have a role. We don't know the effect of each on cardiovascular health; we need to look at that a little more carefully because we've ignored subcutaneous fat. I think that's a very important point made by this paper. Some of the assumptions that we've made could be wrong, or need to be altered."

Dr. Swanson also observed a significant decrease in mean white blood cell count 3 months after liposuction only (11%; 7030 to 6250 cells/μL; P < .001) and after liposuction with abdominoplasty (12%; 7220 to 6330 cells/μL; P < .001). Previous investigations have found that individuals with higher mean leukocyte counts (8800 cells/μL) have a significantly greater risk for coronary heart disease than those with levels closer to 5600 cells/μL.

No significant changes were recorded in total cholesterol, low-density-lipoprotein cholesterol, or high-density-lipoprotein cholesterol.

"We know...that lower triglyceride levels and lower white counts tend to be associated with fewer health risks," Dr. Swanson concluded. "However, nobody has actually followed a group of patients after liposuction of a period of years to see if they encounter fewer medical problems. This is the logical next step."

Dr. Swanson and Dr. Aly have disclosed no relevant financial relationships.

Plastic Surgery 2011: American Society of Plastic Surgeons (ASPS) Annual Meeting. Presented September 25, 2011.

By: Rod Franklin

Acetaminophen: Repeated Use of Slightly Too Much Can Be Fatal

November 22, 2011 — Repeated doses of slightly too much acetaminophen (known as paracetamol in the United Kingdom and elsewhere in Europe) can be fatal, according to the results of a large, single-center cohort study published online November 22 in the British Journal of Clinical Pharmacology.

"On admission, these staggered overdose patients were more likely to have liver and brain problems, require kidney dialysis or help with breathing and were at a greater risk of dying than people who had taken single overdoses," senior author Kenneth J. Simpson, MBChB (Hons), MD, FRCP (Edin), from the University of Edinburgh and Scottish Liver Transplant Unit in the United Kingdom, said in a news release.

"They haven't taken the sort of single-moment, one-off massive overdoses taken by people who try to commit suicide, but over time the damage builds up, and the effect can be fatal," he adds.

In the United Kingdom, acetaminophen hepatotoxicity is the leading cause of acute liver failure (ALF). However, the effect of a staggered overdose pattern or delayed hospital presentation on mortality or need for emergency liver transplantation was previously unknown.

Of 663 patients admitted with acetaminophen-induced severe liver injury between 1992 and 2008, 161 (24.3%) had taken a staggered overdose. Compared with patients who took an overdose at a single time, patients with staggered overdose were significantly older and more likely to abuse alcohol.

When asked why they repeatedly ingested more than the recommended dose of acetaminophen, patients with staggered overdose most often cited pain relief as their rationale (58.2%).

Compared with patients who took an overdose at a single time, those who took staggered overdoses had lower total ingested doses and lower serum alanine aminotransferase (ALT) levels on admission. 

Nonetheless, they were more likely to be encephalopathic and to require renal replacement therapy or mechanical ventilation.

Although mortality was higher in staggered overdoses than in single-time overdoses (37.3% vs 27.8%; P = .025), the staggered overdose pattern was not an independent predictor of mortality. For staggered overdoses, sensitivity of the King's College poor prognostic criteria was reduced (77.6%; 95% confidence interval [CI], 70.8% - 81.5%).

Delayed presentation to medical services more than 24 hours after single-time overdose occurred in 44.9% of those in whom accurate timings could be determined, and was independently associated with death or liver transplantation (odds ratio [OR], 2.25; 95% CI, 1.23 - 4.12; P = .009).

In their logistic regression analysis, the investigators controlled for signs and symptoms, such as hepatic encephalopathy and prothrombin time, as well as various demographic factors.

"Staggered overdoses or patients presenting late after an overdose need to be closely monitored and considered for the paracetamol antidote, N-acetylcysteine [NAC], irrespective of the concentration of paracetamol in their blood," Dr. Simpson said.

Because both these groups are at increased risk of developing multiorgan failure, they should be considered for early transfer to specialist liver centers.

Limitations of this study include reliance on patient recall regarding the time of last ingestion, total paracetamol dose, and suicidal intent; limited data regarding the use of concomitant P450 enzyme inducers or recent fasting; and selection bias for the more severe cases of acetaminophen toxicity in Scotland.

"[T]his large cohort study demonstrates the deleterious effects of delayed presentation and staggered overdose pattern upon outcome following paracetamol-induced acute liver injury," the study authors conclude. "Both delayed presentation > 24 hours and staggered overdoses are strongly associated with multiorgan injury and the need for [liver transplantation]. Patients presenting with these overdose patterns should be treated as high risk for progression to ALF, and should receive NAC in their presenting hospital whilst awaiting serial ALT and PT levels."

By Laurie Barclay

The Pill and Prostate Cancer: Is There a Link?

November 16, 2011 — Countries where oral contraceptive use among women is high appear to have correspondingly higher rates of prostate cancer, according to a study published online November 14 in BMJ Open.

Several recent studies have suggested that estrogen exposure increases the risk for prostate cancer, David Margel, MD, from the Princess Margaret Hospital, University of Toronto, Ontario, Canada, told Medscape Medical News.

This could be because the residue of estrogen ends up in the water supply and the food chain, he said.

"We believe that this is due to an environmental effect," Dr. Margel said. "These oral contraceptives contain a small amount of estrogenic compounds, which are not biodegradable and are excreted in the urine. Although each woman takes these compounds at very minimal doses, when millions of women take them, and for a long period of time, there may be some effect on the environment."

Together with coauthor Neil E. Fleshner, MD, head of the division of urology at the University of Toronto Health Sciences Center, Dr. Margel decided to examine this association in an ecological study.

They used data from the International Agency for Research on Cancer to examine age-standardized rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report to determine the proportion of women taking the birth control pill or using other means of contraception, including condoms, intrauterine devices (IUDs), and vaginal barriers.

They then analyzed the data for 87 countries, and correlated the percentage of oral contraceptive use with the number of new cases of prostate cancer and the number of deaths due to prostate cancer in each country.

They found that the use of IUDs, condoms, and other vaginal barriers was not associated with an increased risk for prostate cancer.

However, throughout the world, oral contraceptive use was associated with a significantly increased incidence of prostate cancer (r = 0.61; P < .05) and death from prostate cancer (r = 0.53; P < .05).

The researchers controlled for each country's wealth, but found no correlation between wealth and prostate cancer risk or mortality. However, "wealth may be associated with prostate cancer, because the wealthier the country, the higher the likelihood of screening for prostate cancer, and with screening comes more prostate cancer," Dr. Margel said.

He stressed that these findings are observational and do not indicate a cause-and-effect relation between oral contraceptive use and prostate cancer.

Importantly, "we are in no way telling women to get off the Pill," he added.

"In the future, to help us understand this phenomenon, we want to look at water supplies and test the estrogenic levels. We also want to look at prostate tissue to see if there are differences in estrogenic levels between those with prostate cancer and those without," Dr. Margel said.

For now, the study is just meant to cause people to take note of a potential harmful effect that the use of estrogen-disruptive compounds might be having.

"We hope this provokes other people to become interested in this topic, not only for oral contraceptives but for other endocrine-disruptive compounds that may be in the environment and may affect our health," Dr. Margel said. "We don't have a solution; we just hope that this will open up more research in this area."

Hypothesis-Generating Study

 

"This study is hypothesis generating, but in terms of the evidence the authors present to support estrogen as a potential cause of prostate cancer, it is too early to say," said Jian-Min Yuan, MD, PhD, epidemiologist and newly appointed associate director of the University of Pittsburgh Medical Center (UPMC) Cancer Institute in Pennsylvania.

"They used aggregate data for each country's use of oral contraceptives to correlate with aggregate data of prostate cancer rates, but these are just correlations. There are no underlying biological mechanisms, at least not as yet, to show that oral contraceptives are a cause," explained Dr. Yuan, who also heads the cancer epidemiology, prevention, and control program at UPMC, and is professor of epidemiology at University of Pittsburgh's School of Public Health.

Dr. Yuan added that rates of prostate cancer in developing countries appear low, but this probably has nothing to do with the use, or lack thereof, of the Pill.

"There could be some kind of biological mechanism that we just don't understand yet. The belief that estrogen causes prostate cancer could be tested in animal models," Dr. Yuan noted.

Weighing in with his opinion about the study, Edwin van Wijngaarden, MD, from the University of Rochester Medical Center, in New York, told Medscape Medical News that the notion that men with more exposure to endocrine-disrupting chemicals, presumably from the drinking water, are at higher risk for prostate cancer seems speculative.

"All these data can tell you is that, on average, countries with higher oral contraceptive use have a higher prostate cancer incidence. This relationship could have many explanations, even at the country level, as they only controlled for gross domestic product per capita," Dr. van Wijngaarden said.

Like Dr. Yuan, Dr. van Wijngaarden believes that the study has generated an interesting hypothesis, "which is the only thing papers like this can do." However, he said, "it is far removed from being able to say that oral contraceptive use and prostate cancer are linked on a population level, let alone causally on an individual level."

By: Fran Lowry

Panel Recommends Universal Cholesterol Screening for Kids

November 13, 2011 (Orlando, Florida) — An expert panel is recommending that all children, regardless of family history, undergo universal screening for elevated cholesterol levels [1]. The panel recommends that children undergo lipid screening for nonfasting non–HDL-cholesterol levels or a fasting lipid panel between the ages of 9 and 11 years followed by another full lipid screening test between 18 and 21 years of age.

The guidelines, from the Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, appointed by the National Health, Lung, and Blood Institute (NHLBI) and endorsed by the American Academy of Pediatrics (AAP), also recommend measuring fasting glucose levels to test for diabetes in children 10 years of age (or at the onset of puberty) who are overweight with other risk factors, including a family history, for type 2 diabetes mellitus.

"The goal of the expert panel was to develop comprehensive evidence-based guidelines that address the known risk factors for cardiovascular disease to assist all primary pediatric care providers in both the promotion of cardiovascular health and the identification and management of specific risk factors from infancy into young adult life," write panel chair Dr Stephen Daniels (University of Colorado School of Medicine, Denver) and colleagues in Pediatrics.

The level of evidence supporting the "strongly recommended" cholesterol screening recommendation is graded B, meaning that it is based on consistent evidence from observational studies, genetic natural history studies, or diagnostic studies with minor limitations. However, as some critics have pointed out, there are no randomized, controlled, clinical trials showing that the treatment of elevated cholesterol levels in children has a long-term clinical impact on cardiovascular outcomes, as well as no data showing that the use of lipid-lowering drugs is safe in children this young or when used for decades.

In addition to the publication, Daniels and members of the writing committee plan to present their report at the American Heart Association 2011 Scientific Sessions this week.

Not Going to Have a Heart Attack Tomorrow

 

Dr Steven Nissen (Cleveland Clinic, OH), who was not part of the writing committee, called the guidelines "irrational," saying pediatricians have pushed widespread cholesterol screening forward in the absence of evidence supporting pharmacologic interventions if children are found to have elevated LDL-cholesterol levels. Nissen told heartwire that while the guidelines stress dietary and lifestyle intervention in kids with elevated cholesterol levels, the temptation to use the drugs in this population will be too high. "Plus, what is the 20-year risk of cardiovascular disease in a patient who is 11 years old?" asked Nissen. "It's zero."

What is the 20-year risk of cardiovascular disease in a patient who is 11 years old? It's zero.

In their recommendations, the expert panel acknowledged that a focus on cardiovascular risk reduction in children and adolescents is tough, because the likelihood of a clinical end point of manifest cardiovascular disease is remote.

Speaking with heartwire , Dr Daphne Hsu (The Children's Hospital at Montefiore, NY) took a different interpretation of the guidelines but acknowledged that pediatricians are forced to infer how risk factors might translate into clinical outcomes 30 to 40 years down the road. Still, she said there are data showing a risk of subclinical atherosclerosis in young patients with elevated cholesterol levels. Moreover, the new recommendations cull together the best data currently available, and based on her assessment of the risks of screening and the potential benefits, the new AAP/NHLBI guidelines make sense. As for the risks, Hsu does not believe that universal screening will lead to an increased use of cholesterol-lowering medications, such as statins.

"If we find a patient has elevated cholesterol levels, we know their risk is not very high, and it is not going to be high enough to warrant treatment, but the screening could be enough to spur changes in behavior," said Hsu. "If they have elevated levels, we can then begin to look for why this is the case, and we can look for ways to change their eating habits, change what they eat, and change how often they exercise."

Hsu said that it was "highly unlikely" that screening would lead to more children being treated with cholesterol-lowering medications, probably less than 1%. She said the greatest benefit would be to children with major lipid disorders who might have been missed with other screening tools. She said the 2008 AAP document on lipid screening and cardiovascular health provides guidance on treatment with pharmacologic agents. Written also by Daniels and Dr Frank Greer (University of Wisconsin Medical School, Madison), along with the Committee on Nutrition, the document says that treatment should be started if LDL-cholesterol levels are higher than 190 mg/dL [2]. The cutoff point for therapy is 160 mg/dL for children with other risk factors, with targets as low as 130 mg/dL or even 110 mg/dL when there is a strong family history of cardiovascular disease, especially with other risk factors, such as obesity, diabetes, metabolic syndrome, and other higher-risk situations.

An Age When They'll Listen to You

 

In her practice, Hsu said she sees firsthand the epidemic of childhood obesity, with many young children having pre-metabolic syndrome. With screening of children aged 9 to 11 years old, she believes they are at a vulnerable age that might be more responsive to recommendations from their family doctor, whereas older children, particularly teenagers, don't like being told what to eat or how much to exercise. She said cholesterol screening can signal potential long-term complications and can serve as an increased wake-up call for families.

"We're not telling the kids or families that they're going to have a heart or stroke tomorrow but instead saying that we want them to live until they're 85 years old," said Hsu. "We want to see them live longer than their grandmother or grandfather."

Nissen, on the other hand, isn't buying the argument, stating there is no evidence-based data showing that young patients or their families change their behavior when presented with evidence of a bad test result, such as increased cholesterol levels. Proponents of other screening modalities have made similar arguments in the past, suggesting that evidence of calcification or stenosis is a motivating factor to move toward heart-healthy behaviors, but the data do not bear this out.

Earlier this year in the Journal of the American Society of Echocardiography, researchers reported that abnormal findings on an office-based carotid ultrasound test changed physician behavior, with doctors changing their use of aspirin and cholesterol-lowering medications, including setting more aggressive lipid and blood-pressure targets [3]. Patients, on the other hand, failed to make changes to their diet or increase physical activity levels and, in some instances, even failed to quit smoking, despite an increased awareness of their cardiovascular-disease risk.

"Shouldn't we be counseling children on the benefits of healthy eating and lots of physical exercise even without knowing their LDL-cholesterol levels?" said Nissen. "I don't see how screening changes this at all. We simply have no evidence that patients will change their behavior based on more screening."

The expert panel also provides guidance on the assessment of family history of cardiovascular disease, tobacco exposure, nutrition and diet, growth and overweight/obesity assessments, blood pressure, and physical activity.

By: Michael Fiordan

Family History, Alcohol Intake, and Benign Breast Disease

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November 14, 2011 — A young girl's chances of developing benign breast disease (BBD), a known risk factor for breast cancer (BC), appears to double if the patient has a family history of BBD or BC and also consumes alcohol, according to study data published online November 14 in Cancer.

However, alcohol consumption was not associated with an increased of BBD risk for young girls who did not have a family history of BBD or BC. For these participants, smaller increases in BBD risk were associated with control variables such as height, body mass index, and waist circumference.

The results come from the Growing Up Today Study (GUTS), coordinated at the Washington University School of Medicine in St. Louis, Missouri, and focusing on daughters of participants in the Nurses' Health Study II. The new information adds to existing epidemiological evidence that links alcohol use to heightened risk of breast disease, but is the first study to examine alcohol's effect in adolescent girls.

The authors, led by Catherine S. Berkey, ScD, from the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, studied data from 9037 girls from all 50 states.

When initially enrolled in GUTS in 1996, study participants ranged in age from 9 to 15 years. They completed annual questionnaires from 1996 to 2001, and then again in 2003, 2005, and 2007. The 2005 and 2007 surveys revealed that 67 participants had biopsy-confirmed BBD, and 6741 of the respondents to those surveys reported no BBD.

The researchers initially looked at the effect of family history on risk of BBD, independent of alcohol consumption. Using logistic regression models, they report that the risk for BBD was doubled if a girl's mother and/or a maternal aunt had previously been diagnosed with BC (odds ratio [OR], 2.34; P = 0.01, univariate analysis). The daughters of mothers previously diagnosed with BBD faced a less dramatic risk hike for BBD (OR, 1.59; P = .095, univariate analysis).

Within this cohort, alcohol use (7 drinks per week) exacerbated BBD risk in the girls with a family history. Study participants who drank and had any family history of BC (originating with a mother, aunt, or grandmother) had a greater than 2-fold risk of acquiring BBD (OR, 2.28; P = .01). Those who consumed alcohol and whose mothers previously reported BBD only also reflected a heightened risk for BBD (OR, 1.96; P = .02). In contrast, alcohol was not associated with a statistically significant increase in risk for those who had no family history (OR, 1.22; P = .57.

Risk assessments were aligned with age and with level of alcohol consumption. Study authors reported that "girls with any family history of disease (BC or maternal BBD) and who are in the highest quartile of alcohol consumption for their age (≥1 drink/wk for age 16 years, 2 drinks/wk for 18 years, 3 drinks/wk for 19 years) have significantly greater BBD risk (OR, 2.27; P = .03) relative to girls with no family history who do not drink any alcohol."

The a limitations of the study include the small number of BBD cases within certain family history subgroups (particularly mothers with BC and aunts with BC), as well as the potential for a BBD detection bias, owing to the higher likelihood of BBD diagnoses being conducted on girls with a family history of breast health issues compared with those without a family history of complication.

The researchers concluded that reduction of alcohol use during adolescence can affect BBD risk exposure in girls with a family history of breast-related issues. Moreover, the study supports earlier research related to the effect of alcohol on BC risk elevation in women.

By: Rod Franklin

USPSTF Updates Skin Cancer Prevention Counseling Guidelines

From:

November 8, 2011 — To reduce risk for skin cancer, the US Preventive Services Task Force (USPSTF) recommends counseling persons aged 10 to 24 years with fair skin to minimize exposure to ultraviolet (UV) radiation, according to a USPSTF recommendation statement. However, the USPSTF concluded that current evidence is insufficient to weigh the benefits versus the risks of counseling adults older than 24 years of age.

This evidence-based recommendation statement is an update to the previous 2003 USPSTF recommendations about skin cancer counseling by primary care doctors. At that time, the Task Force concluded that there was no evidence for the benefit of counseling in any age group.

"Skin cancer is the most common malignancy in American populations, and is diagnosed in more than 2 million Americans each year," the USPSTF writes. "Convincing evidence relates UV radiation exposure during childhood and youth to a moderately increased risk of skin cancer later in life; for adults, adequate evidence links UV radiation exposure to a small increase in the subsequent risk of skin cancer.…Individuals with a fair skin type are at greatly increased risk of skin malignancy."

Rationale for Behavioral Counseling

The goal of behavioral counseling is to increase sun-protective behaviors shown to be effective in reducing UV radiation exposure from the sun and from indoor tanning. Recommended interventions include using effective sunscreen, wearing hats or other shade-protective clothing, reducing outdoor activities during midday hours, and avoiding the use of indoor tanning.

Risk for skin cancer is greatly increased among persons with a fair skin type, defined as light pigmentation, light hair and eye color, freckles, and a tendency to sunburn easily. Most studies of interventions to increase sun-protective behaviors have enrolled only persons with a fair skin type.

Adequate evidence suggests that for persons aged 10 to 24 years, counseling interventions available in or referable from primary care can moderately increase the use of sun-protective behaviors. However, evidence is inadequate to assess the effect of counseling on the use of sun-protective behaviors by adults older than 24 years of age.

Evidence is adequate that no appreciable harms are associated with counseling or sun-protective behaviors in youth or adults. Little evidence supports theoretical concerns about sun-protective behaviors increasing the risk for vitamin D deficiency in adults living in northern latitudes.

The USPSTF therefore concluded with moderate certainty that there is a moderate net benefit of counseling for persons aged 10 to 24 years with fair skin. However, the balance of benefits and harms cannot be determined for adults older than age 24 years, because evidence is sparse and of unknown clinical significance.

Specific USPSTF Recommendations

Specific USPSTF recommendations regarding behavioral counseling to prevent skin cancer are as follows:

• To reduce risk for and prevent incidence of skin cancer, the USPSTF recommends counseling children, adolescents, and young adults aged 10 to 24 years who have fair skin about minimizing their exposure to UV radiation (grade B recommendation).
• The USPSTF concludes that current evidence is insufficient to determine the balance of benefits and harms of counseling adults older than age 24 years about minimizing their risks to prevent skin cancer (I statement).

Overall, these recommendations are consistent with those of other professional societies. The American Cancer Society recommends protecting children from the sun because severe sunburns in childhood increase the risk for skin cancer. The American Academy of Family Physicians is updating its recommendations about counseling to prevent skin cancer, although previous statements have been consistent with those of the USPSTF.

The American Academy of Pediatrics has issued comprehensive guidelines to protect children from UV radiation exposure and recommends that pediatricians include sun safety advice in health maintenance visits at least annually.

Clinical Implications

• The USPSTF recommendation applies only to asymptomatic persons with no history of skin cancer.
• The recommendation for counseling persons aged 10 to 24 years is limited to those with a fair skin type because most trials of skin cancer counseling enrolled only persons with that skin type.
• Counseling adults is of uncertain potential benefit because of the unknown effectiveness of counseling interventions to change behavior and because the association between behavior change in adulthood and skin cancer risk is not well demonstrated. The authors suggest that UV exposure after 35 years of age may contribute much less to lifetime skin cancer risk compared with exposure earlier in life.
• Effective interventions are typically of low intensity and can be carried out during the primary care visit. Messages targeting appearance are most effective in late-adolescent females, with techniques including self-guided booklets, a video on photoaging, 30-minute peer counseling sessions, and UV facial photography to demonstrate the extent of skin damage from UV exposure.

"Further randomized, controlled trials are needed to develop effective interventions for infants and small children," the USPSTF concludes. "In addition, a better understanding of the impact of UV exposure during adulthood, in terms of risk of skin malignancies, would be valuable to address the key evidence gap around counseling for that age group. Research is also needed to further develop technologies and vehicles for administering relevant interventions for behavior change."

By: Laurie Barclay, MD