NEOADJUVANT CHEMOTHERAPY FOR ALL WOMEN UNDER 35?

Neoadjuvant chemotherapy might be particularly critical for very young women with certain early breast cancers because of biologic differences in their tumors, according to research presented here at the 35th Annual San Antonio Breast Cancer Symposium.

"I would personally approach all young women with these cancers by suggesting neoadjuvant chemotherapy," said lead investigator Sibylle Loibl, MD, PhD, from the University of Frankfurt in Germany. "Some people think they don't need chemotherapy at all, but I think they do," she explained.

"Breast cancer in the very young woman seems to be different.... There is something behind age that drives the biology of the cancer and makes it more chemo-responsive," she noted.

In a meta-analysis of 8 trials involving 8949 patients, Dr. Loibl and her colleagues found that women younger than 35 years were more likely to achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy than women 36 to 51 years (23.6% vs 17.5%) and than women older than 51 years (13.5%; P < .0001).

Additionally, those with a pCR saw benefits in both disease-free survival and local recurrence-free survival, she said.

The superior pCR rate in young women after chemotherapy was driven by better pCR in 2 types of tumors: triple-negative tumors and luminal-like tumors, she added.

Specifically, women 35 years and younger achieved higher rates of pCR in triple-negative tumors than women 36 to 51 years (45% vs 35%) and than women older than 51 years (25%; P = .004).

Similarly, women 35 years and younger achieved higher rates of pCR in luminal-like tumors than women 36 to 51 years (approximately 11% vs 8%) and than women older than 51 years (6%; P = 0.013).

She said she expects the findings will influence clinical practice.

"I think the luminal-like patients, when they're very young, will be treated more often now with chemo. For women with triple-negative tumors, it's reassuring; we can tell them you have an almost 50% chance that everything will be gone and you'll have an excellent survival," she said.

All subjects in the meta-analysis received neoadjuvant anthracycline/taxane–based chemotherapy, and some received trastuzumab.

Generally, "in younger women, we tend to be more aggressive with chemotherapy," said Carlos Arteaga, MD, PhD, associate director of clinical research and director of the breast cancer program at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, during a meeting press conference.

"The importance of this study is that it suggests there are some biological differences that go beyond luminal B that we have to study," he said.

Dr. Loibl and Dr. Arteaga have disclosed no relevant financial relationships. Study coauthor Gunter von Minckwitz, MD, PhD, reports being a consultant/advisor for sanofi-aventis, Roche, Amgen, AstraZeneca, Boehringer, and Eisai; and conducting scientific studies/trials for Amgen, Pfizer, GSK, sanofi-aventis, Roche, Novartis, BMS, Celgene, Cephalon, Boehringer Ingelheim, and Eisai. Coauthor Carsten Denkert, MD, reports receiving grant/research support from Siemens Medical Solutions and Sividon Diagnostics; consulting for Celgene, Amgen, and Sividon; and being a shareholder in Sividon Diagnostics. Coauthor Christian Jackisch, MD, reports being on the speaker's bureau for Roche and GSK. Coauthor Michael Untch, MD, reports receiving grant/research support from and being a consultant for Bristol-Myers Squibb and Amgen.

The Weight-Loss Nutrient You're Not Eating

Fiber: Weight-loss superfood?The U.S. often isn't the first nation to come to mind when you think of countries with healthy eating habits to adopt, but it turns out we may be influencing how our friends across the Atlantic dine.

The "all things fiber" trend taking over American supermarkets is also on the rise in Spain, Germany, Poland, and the U.K., where 62 percent of people say consuming enough fiber is important, a new European report found. Fiber even trumps calories, as only 56 percent said reducing calories was important.

This study intrigued me because while there are a number of foods with fiber added on the market-everything from pasta to yogurt-the latest nutrition data indicates that the average intake in the United States is less than half the recommended 14 grams per 1,000 calories (which works out to roughly 25 grams a day for women and 38 for men). And when I talk to my clients, most don't know much about this nutrient, other than it's generally good for you.

In a nutshell, fiber is a type of carbohydrate that your body can't digest or absorb, and there are two primary types: soluble and insoluble. Soluble is the soft, sticky type found in oats, barley, beans, and the "meat" of fruits, which helps to lower cholesterol and soften waste so it can pass through your system more easily. Insoluble is the tough type, found in whole wheat and the skin, stalks, and seeds of fruits and veggies, that helps to push waste through the GI tract and improve bowel regularity.

Fiber also has a number of weight-control benefits, which I've often touted on this blog. First, it fills you up, but because you don't break it down and absorb it into your bloodstream, you don't have to worry about burning off fiber in order to prevent it from getting socked away in your fat cells.

There is also some research showing that for every gram of fiber you eat, you eliminate about seven calories. That means if you gobbled 30 grams a day, it would essentially "cancel out" 210 of the calories you ate, which could result in shedding up to 20 pounds in a year's time.

Lastly, fiber has been found to slow the digestion and absorption of other carbs, which results in a slower, steadier rise in blood sugar and a delay in the return of hunger.

RELATED: In addition to fiber, be sure you're eating these eight super nutrients that help you slim down.

But fiber's powers don't stop at weight loss. It may also reduce the risk of death from any cause, according to a recent paper in the Archives of Internal Medicine. Women who ate about 25 grams of fiber a day were 22 percent less likely to die during the nine-year study than those who ate only 10 grams daily. And the risk of death from heart disease, infections, and respiratory diseases was reduced by as much as 50 percent in in the high-fiber eaters, with the greatest benefit seen from consuming grains. Pretty powerful stuff!

To boost your intake and hit the daily target, I recommend bulking up on naturally fiber-rich foods, primarily fruits, veggies, whole grains, beans, and nuts. Just a cup of raspberries, a cup of black bean soup, a medium orange, and an ounce of almonds packs more than 25 grams, so meeting the recommendation doesn't require a drastic change in your diet.

Some good general rules of thumb for upping your intake include:

• Choose more fruits with edible seeds, skins, and membranes, including apples, raspberries, and oranges.
• Reach for veggies with tough stalks and edible skin, such as artichokes and broccoli.
• Opt for whole rather than refined grains. Oats, barley, quinoa, brown and wild rice, and 100% whole-wheat versions of bread, pasta, and crackers are good options.
• Replace meat with beans or lentils at least five times a week.
• Snack on nuts and seeds, or use them to garnish salads, stir-fries, cereal, and yogurt.

Oh, and one more thing: As you increase your fiber intake, be sure to drink plenty of extra water. It's key to help the fiber move through your system. Too little H2O and too much fiber can be a recipe for bloating and constipation, or a pretty uncomfortable tummy ache!

CELL PHONE ADDICTION

Cell phone use and text messaging can become as addictive as any other behavior, such as compulsive shopping, gambling, and overeating, new research shows.

Investigators from Baylor University in Waco, Texas, found that both materialism and impulsiveness drive addictive tendencies toward cell phone use and text messaging.

"People understand substance addictions. They understand that we can take a drug that impacts parts of our brain and reinforces the pleasure principle, so we're addicted to that particular substance. But it's no different with behavioral addiction," said lead investigator James Roberts, PhD, in a video clip in which he discussed the study.

"We get some kind of reward from the use of our cell phone that produces pleasure — a lot of dopamine and serotonin in our brain — that keeps us coming back. So I think, and the research tells us, that behavioral addictions like cell phone addiction are just as real as substance addiction."

The article was published online November 17 in the Journal of Behavioral Addictions.

Materialism, Impulsiveness

The study included 191 business students at 2 US universities who completed a paper and pencil survey administered during class.

The questionnaire took approximately 15 minutes to complete and contained scales that measured materialism, impulsiveness, and mobile phone and instant messaging use.

Addictive tendencies toward mobile phone use and instant messaging were measured by mobile phone technology addiction (MPAT) and instant messaging technology addiction (IMAT) scales; responses were recorded on a 7-point Likert scale.

Mean scores for MPAT and IMAT were 5.06 and 2.52, respectively.

Impulsiveness was measured using Puri's 12-item scale, in which students were asked to rate how well 12 adjectives described them. The mean impulsiveness score was 3.2.

Materialism, best understood as the importance placed on worldly possessions, was measured using Mowen's 4-item scale. For this scale, respondents were asked to rate how accurately 4 personality traits described them.

On each of the respective scales, a higher score reflected a higher level of dependency, impulsiveness, or materialism.

Greater Potential for Addiction?

Results showed that both materialism ( P < .001) and impulsiveness ( P = .029) significantly predicted MPAT scores. Similarly, materialism ( P = .001) and impulsiveness ( P = .029) significantly predicted IMAT scores.

"Note that the impact of materialism on either addictive behavior is large relative to that of impulsiveness," the authors write.

The larger effect that materialism had on cell phone use in the current study relative to texting may also reflect the fact that cell phones are a sign of conspicuous possession.

In contrast, texting may be seen more as a private engagement and does not signal any particular status.

Dr. Roberts noted that whenever people display addictive behavior, it has negative effects on quality of life.

With cell phone and texting addiction, "it's an opportunity cost, so we are crowding out so many more important activities, including family and friends and other pursuits, that might bring us true happiness," he said.

Furthermore, cell phones are becoming "increasingly dangerous," because they offer more and more opportunities to interact with them, so their potential for addiction is greater, Dr. Roberts added.

Caution Warranted

Petros Levounis, MD, Columbia University College of Physicians and Surgeons, New York City, toldMedscape Medical News that gambling and compulsive sexual behavior come closer to the definition of frank addiction than cell phone and texting behaviors.

"We also have a long way to go before we develop reliable diagnostic criteria [for cell phone addiction and texting] to guide us in further research and clinical practice," he added.

On the other hand, Dr. Levounis does believe that the symptoms of those with these new technological addictions "share a lot of similarities with the more classic addictions of alcohol and drug abuse."

Journal editor Zsolt Demetrovics, PhD, Eötvös Loránd University, Budapest, Hungry, agreed that excessive use of cell phones and texting has similar characteristics to other addictions.

On the other hand, Dr. Demetrovics was uncertain whether overuse of cell phones should be viewed in the same light as a classic addiction.

"To consider something as a disorder or illness, the behavior must impair one's life significantly. And at this moment, we do not see these dramatic consequences in a large population," he told Medscape Medical News.

Nevertheless, Dr. Demetrovics believes it is important to pay attention to these behaviors, especially because they can cause some harm.

"But we should not overdramatize them as serious illnesses," he emphasized.

Weight loss surgery tied to increase in drinking

People who had weight loss surgery reported greater alcohol use two years after their procedures than in the weeks beforehand, in a new study.

"This is perhaps a risk. I don't think it should deter people from having surgery, but you should be cautious to monitor (alcohol use) after surgery," Alexis Conason, who worked on the study at the New York Obesity Nutrition Research Center at St. Luke's-Roosevelt Hospital Center, told Reuters Health.

Researchers said it's possible some patients may turn to drinking if surgery successfully stops their ability to overeat without addressing their underlying issues. Or, the effects of certain types of stomach-shrinking procedures on alcohol tolerance may influence drinking habits.

Still, the new study can't show whether people were drinking in a dangerous way - and there was no clear increase in drug use or smoking after surgery.

"This does not mean that everyone who has gastric bypass surgery has problems with alcohol or becomes an alcoholic," said Conason.

Her team's study involved 155 people getting gastric bypass or gastric banding surgery, mostly women. Participants started the study with an average body mass index, or BMI, of 46 - equivalent to a five-foot, six-inch person who weighs 285 pounds.

Surgery is typically recommended for people with a BMI of at least 40, or at least 35 if they also have health problems such as diabetes or severe sleep apnea.

Alcohol use dropped immediately following surgery, from 61 percent of people who initially reported drinking to 20 percent at one month post-surgery.

But by three months, drinking rates had started to creep back up. And at two years out, people were drinking significantly more often than before their procedures, according to findings published Monday in the Archives of Surgery.

That was primarily the case for those who had gastric bypass surgery, not banding. On a scale from 0 to 10 of drinking frequency, where 0 represented never, 5 was sometimes and 10 always, gastric bypass patients reported an increase from 1.86 before surgery to 3.08 two years later.

CHANGES IN TOLERANCE
Conason said gastric bypass, in particular, has been shown to drastically lower alcohol tolerance - to the point that some post-surgery patients have a blood alcohol content above the legal driving limit after just one drink. For some, that could make drinking more appealing, she added.
The new findings are "proving more support for the idea that we really need to talk to patients about alcohol use, especially those undergoing (gastric bypass)," said Wendy King, an epidemiologist and weight loss surgery researcher at the University of Pittsburgh, who wasn't part of the study team.

According to the American Society for Metabolic and Bariatric Surgery, about 200,000 people have weight loss surgery every year. The procedures cost about $20,000 each.

Although some researchers have questioned the long-term benefits of surgery, one recent study found three-quarters of people who'd undergone gastric bypass had lost and kept off at least 20 percent of their initial pre-surgery weight six years later (see Reuters Health story of September 18, 2012).

One limitation of the new study is that only one-quarter of the initial participants were still in touch to report their current alcohol and drug use at the two-year mark - so the researchers don't know how everyone else fared.

Psychiatrist Dr. James Mitchell, who has studied alcohol use after weight loss surgery at the University of North Dakota School of Medicine and Health Sciences in Grand Forks, said there's also a need for research going out more than two years - to see if alcohol use keeps increasing.

Researchers said people who've had weight loss surgery should talk with their doctors soon if they notice themselves wanting to drink more.

"The health risks of obesity are such that people with severe obesity should not forgo bariatric surgery because of this," Mitchell, who was not involved in the new study, told Reuters Health.

But he said everyone should be warned about this possibility - and people with a history of alcohol abuse should be particularly careful.

"I don't have the impression (doctors) are talking a tremendous amount about these things," Conason said. "I think we should be. I think we should be educating patients about all the potential risks and benefits."

NEW CLASS OF DRUGS FOR OSTEOPOROSIS-CATHEPSIN K INHIBITORS

The investigational agent odanacatib appears to be an effective treatment for postmenopausal osteoporosis that persists after 3 years of alendronate therapy, according to a phase 3 trial presented here at ACR 2012.

Treatment with odanacatib significantly improved bone mineral density (BMD) at the femoral neck, hip, trochanter, and lumbar spine, compared with placebo, in postmenopausal women previously treated with alendronate. In addition, the novel agent was generally safe and tolerable.

The phase 3 trial was stopped early after an independent data and safety monitoring committee determined that odanacatib had a favorable risk/benefit profile.

"Odanacatib is a cathepsin K inhibitor that inhibits bone resorption while maintaining bone formation, whereas bisphosphonates reduce bone resorption and bone formation," said lead author Roland Chapurlat, MD, from Hôpital Edouard Herriot in Lyon, France.

"In this study of women with low bone mass after alendronate treatment, we saw no issues of excess bone formation or abnormal stress fractures," he explained.

Dr. Chapurlat noted that most studies of women with osteoporosis do not enroll previously treated women, but this study sought to determine if the drug had a benefit in previously treated patients.

The randomized double-blind placebo-controlled 24-month trial was conducted at 42 sites in 12 countries. Investigators enrolled 246 women 60 years or older with osteoporosis, and randomly assigned them to receive odanacatib 50 mg once weekly or placebo. All patients received vitamin D and calcium supplementation.

The mean age of the participants was 71.3 years, most were white, 73.7% had a history of any fracture, and 68.3% had a fracture history after menopause. The mean duration of previous alendronate therapy was 5.5 years; 55% had taken alendronate for 3 to 5 years.

"Long-term alendronate [treatment] results in persistent suppression of bone turnover, and there is a residual effect even after stopping," Dr. Chapurlat said.

For the primary end point of femoral neck BMD at 24 months, there was a 2.67% difference favoring odanacatib ( P < .001), and for total hip BMD, there was a 2.7% difference favoring odanacatib ( P < .001). For both these end points, the effect of odanacatib was seen after 6 months because of the residual effect of alendronate, Dr. Chapurlat reported.

A 3.18% difference in BMD at the trochanter and a 2.57% difference in BMD at the lumbar spine also favored odanacatib at 24 months ( P < .001 for both, compared with placebo).

At 24 months, odanacatib significantly reduced markers of bone resorption ( P < .001) and significantly increased markers of bone formation ( P = .011).

There were no significant differences in adverse events in the 2 treatment groups, although the rate of discontinuations related to adverse events was higher in the odanacatib group than in the placebo group (9% vs 3%).

The rate of fracture was lower in the odanacatib group than in the placebo group (4.9% vs 13.2%). "The study was not designed to look at fracture efficacy," Dr. Chapurlat stated.

An ongoing phase 3 trial of 16,000 women will show fracture rate; those results are expected next year, he said.

In contrast to bisphosphonates, odanacatib and denosumab are not deposited in the bone, so they should not have a long-term effect on bone turnover after drug discontinuation.

"They block osteoclasts and don't reside in the bone," said Stanley Cohen, MD, medical director of the rheumatology training program, clinical professor of internal medicine at the University of Texas Southwestern Medical School in Dallas, and past president of the ACR.

"What happens to patients who were taking alendronate and still have low bone mass? Will they respond with improvement in bone density? The answer is yes," Dr. Cohen stated.

Dr. Cohen doubts that odanacatib will replace bisphosphonates "because they cost pennies and their benefits are outstanding. But we need to define better which patients should be treated and for how long, in light of the rare cases of atypical fracture reported with long-term treatment," he said.

If long-term follow-up shows that odanacatib does reduce bone resorption and allows new bone formation to continue, this drug is likely to play a role in the treatment of osteoporosis, Dr. Cohen said.