Herceptin 'Revolutionary' for Breast Cancer
Studies Confirm Survival Benefit When Drug Used Early
In May 2005, oncologists attending the annual meeting of the American Society of Clinical Oncology heard presentations about the breast cancer drug Herceptin (trastuzumab) that many considered a treatment breakthrough. Researchers had found that using Herceptin early in the course of breast cancer could cut recurrences in half and improve survival for women with a particularly aggressive form of the disease.
Now those studies have been published, giving doctors and patients more details about the advantages and side effects of this new treatment strategy. They appear in this week's issue of the New England Journal of Medicine and are again being hailed by experts.
"Clearly, the results reported in this issue of the journal are revolutionary," writes Gabriel Hortobagyi, MD, in an editorial discussing the findings. Hortobagyi is professor and chair of Breast Medical Oncology at the University of Texas M.D. Anderson Cancer Center in Houston and a noted expert in the field of breast cancer care. He was not involved in the studies.
The published reports justify the excitement generated by the presentations earlier this year, according to Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society.
"There's always that nagging caution that maybe the results were premature, or that perhaps the data wasn't accurately analyzed, or that the study was not as well done as it seemed at the time," he said. "Experience has taught us that it is usually best to wait until the study is published in a peer-reviewed journal before accepting it as truly legitimate."
The newly published studies do not disappoint. "The editorial says the results are 'stunning' and I certainly agree," he said.
Thousands of Women Could Benefit
Herceptin is a monoclonal antibody, a targeted drug that only works in breast cancers that have too much of a protein called HER2/neu. About 15%-25% of breast cancers are HER2-positive. These cancers tend to grow quickly and do not respond as well to certain types of chemotherapy or to tamoxifen.
Until now, Herceptin has been used only in women whose breast cancer has returned after initial treatment or spread beyond the breast. These new reports, however, promise to change the standard of care for women with early-stage breast cancer that is HER2-positive.
"Our care of patients with HER2-positive breast cancer must change today," Hortobagyi writes.
Herceptin Given After Adjuvant Chemotherapy
The first report in the journal presents the results of the HERA trial, an international study that compared women who took Herceptin after adjuvant chemotherapy to women who had no further treatment after chemotherapy. All of the women had cancers that overexpressed the HER2/neu protein. The women had all received standard treatment with surgery and tamoxifen (if they had hormone-responsive tumors). Researchers excluded women whose cancers had already spread to the skin, chest wall, distant lymph nodes, or other parts of the body, as well as women with heart problems (including congestive heart failure, angina, unstable heart rhythms, and poorly controlled high blood pressure).
The researchers randomly assigned 1,694 women to take Herceptin for 1 year after finishing their chemotherapy. They were taken off the drug if they developed serious heart problems or other severe side effects. Another 1,693 women were assigned to get no further treatment after chemotherapy. (A third group of 1,694 women was assigned to 2 years of Herceptin after chemotherapy, but results are not yet complete for these subjects.)
After 1 year of treatment, Herceptin cut the risk of breast cancer returning almost in half. Just 127 women (7.5%) in the Herceptin group had a relapse, developed a second cancer, or died, compared to 220 women (13%) in the chemotherapy-only group. The researchers calculated that Herceptin improved disease-free survival by 8.4% after 2 years -- a very large amount for a chemotherapy trial, especially after such a short period of time. The type of chemotherapy drug given (various ones were allowed) did not appear to make a difference in outcome.
"This is probably the biggest evidence of a treatment effect I've ever seen in oncology. It's quite remarkable," said Richard Gelber, PhD, of the Dana-Farber Cancer Institute in Boston. Gelber led the statistical analysis on the study.
The researchers did not find a difference in overall survival between the groups of women, but they say one could become evident as the trial continues. The women will be followed through 2008.
There were more side effects in the women who got Herceptin than the women who received no further treatment: 132 women (7.9%) in the Herceptin group had a serious side effect compared to just 75 (4.4%) in the other group. Women taking Herceptin were more likely to develop congestive heart failure and other heart problems -- known side effects of the drug. Still, just 0.5% of women on Herceptin developed severe heart problems. The researchers acknowledge, though, that longer follow-up may show that more heart problems develop down the line.
Herceptin Given Along With Adjuvant Chemotherapy
The second report in the journal describes the combined results of 2 studies (National Surgical Adjuvant Breast and Bowel Project trial B-31 and North Central Cancer Treatment Group trial N9831), which compared women who got Herceptin at the same time as chemotherapy to women who took only chemotherapy. As in the HERA trial, the women in these studies had HER2/neu-positive cancers. They had already received standard treatment with surgery and radiation (if necessary) and with tamoxifen or an aromatase inhibitor (if their tumors were hormone-receptor positive). Women with metastatic cancer or heart problems were excluded. The NEJM report includes results from 2,043 women enrolled in the B-31 trial and 1,633 women enrolled in the N9831 trial.
All the women were given chemotherapy with doxorubicin and cyclophosphamide, followed by paclitaxel. Some of the women in each study were randomly assigned to take Herceptin along with the paclitaxel; they continued taking Herceptin for 1 year.
As in the HERA trial, Herceptin cut the risk of recurrences almost in half. After about 2 years of follow-up, 133 women on Herceptin had had a relapse, second cancer, or had died, compared to 261 women in the group that got only chemotherapy. After about 3 years, 87% of Herceptin patients were still alive and cancer-free, compared to 75% of women who got only chemotherapy. At 4 years, more than 85% of the women on Herceptin were still alive and cancer-free, compared to 67% of women in the chemotherapy-only group. The difference was so significant that the trials were stopped early.
Unlike the HERA trial, researchers conducting these 2 studies did see a significant difference in overall survival between women who took Herceptin and those who did not. More than 91% of patients on Herceptin survived 4 years, compared to about 87% of patients on chemotherapy alone. Overall, 92 women in the chemotherapy-only group died, and 62 women who took Herceptin died.
Heart problems, especially congestive heart failure, were also a problem for women who took Herceptin in these studies. In the B-31 trial, just 4 women (0.8%) who got chemotherapy alone developed congestive heart failure after 3 years, while 31 women (4.1%) in the Herceptin group developed this side effect. In N9831, none of the women on chemotherapy alone developed heart failure, but 20 Herceptin patients (2.9%) did.
Questions Remain Over Side Effects, Scheduling
More research must be done to best determine how to deal with the heart problems that Herceptin can cause, Hortobagyi said. Doctors need to learn how serious these problems are, if they can be reversed, and how long they must be treated.
Researchers also need to find out if it's better to give Herceptin at the same time as chemotherapy, or if it should be taken afterward. From the new reports, it appears that giving Herceptin after chemotherapy may be less damaging to the heart, Hortobagyi writes, but it's not clear whether one of these schedules is more effective at controlling cancer than the other.
Another issue, raised in a second editorial, is how to deal with resistance to Herceptin. Doctors have seen drug resistance develop in some patients, but they don't yet understand how it happens -- or how to stop it.
Exercise can ward off osteoporosis: report
Doctors used to think a good, calcium-rich diet was enough to avoid the crippling bone disease known as osteoporosis, but it is now clear that regular exercise is just as important, a new report released on Thursday said.
"One of the best ways to build and maintain healthy bones is through exercise," Dr Helmut Minne, a leading German osteopath and board member of the International Osteoporosis Foundation (IOF) said in the IOF's new report, "Move it or Lose it."
The IOF is a non-governmental organization of scientific experts and national societies which focus on the disease.
Osteoporosis, in which the bones become fragile and break easily, is one of the world's most common chronic diseases. It strikes one in three women over 50 worldwide -- more than breast cancer -- and one in five men -- more than prostate cancer, the the report said.
Because bone is living tissue which renews itself continuously, it requires regular stimulation from physical activity. Like muscles, bones should be used regularly or they will deteriorate, the report said.
People develop a peak bone mass during their adulthood, which eventually begins to decline.
"Physicians once thought that reaching this peak depended primarily on diet, including sufficient calcium intake and exposure to vitamin D in the skin," the report said.
"But recent studies have (shown) that in laying down the bone foundation that will serve for a lifetime, exercise is just as important as diet," it added.
The report, which was released in Berlin for "International Osteoporosis Day" on Thursday, says women who sit for more than nine hours a day are 50 percent more likely to have a hip fracture than those who sit less than six hours a day.
Exercising the back during middle-age can help prevent vertebrae from weakening or fracturing when people get older, the report said.
Not all types of exercise stimulate bone mass growth. Weight-bearing and high-impact exercise like running or dancing are best for stimulating bone formation.
"Exercise builds strong muscles, which in turn builds strong bones," Minne said. "Exercise also improves muscle control, balance and coordination, and reduces the risk of falling or suffering a fracture during a fall."
Plain soap just fine to kill germs: experts
Proper washing with regular soap and water works just fine to prevent the spread of germs and there is no clear evidence that antibacterial soaps, wipes and other products are any better, scientists told a U.S. advisory panel on Thursday.
U.S. Food and Drug Administration scientists and other experts said studies showed clear benefits from hand washing with plain soap, especially when people are taught when and how long to wash. Data on antibacterial soap was limited, they said.
"There is a lack of evidence that antiseptic soaps provide a benefit beyond plain soap in (the) community setting," said University of Michigan epidemiologist Allison Aiello.
The panel is weighing the risks of such products for consumers and whether the FDA should curb their use because they may help create drug-resistant bacteria.
The FDA, which has been grappling with the issue for more than 30 years, has yet to make a final decision on how to regulate such products, which face many issues similar to antibiotic drugs, but are available over-the-counter.
The agency is asking its advisers to recommend which consumers should use such products. It is also seeking advice on how to decide whether the soaps are effective and what risks it should consider in making its final rule.
"We're reexamining the risks to consumers," said FDA microbiologist Colleen Rogers.
The FDA, which usually follows its experts' advice, could take a variety of actions, from changing product labels to restricting marketing claims.
Soaps with bacterial-killing agents, such as Procter & Gamble Co.'s Safeguard and Henkel's Dial have been used for years are now common households products.
At issue are antibacterial products that include chemicals such as triclosan, which targets a certain enzyme that bacteria need to live and may linger in the environment. Bacteria can mutate to adapt to such chemicals, scientists say.
Doctors and other experts are concerned that excessive use of the products, like overuse of antibiotic drugs, will create bacteria-resistant "superbugs."
"Bacteria are not going to be destroyed. They've been here, they've seen dinosaurs come and go... so any attempt to sterilize our home is fraught with failure," said panelist Dr. Stuart Levy, a microbiologist at Tufts University in Boston.
Signs of drug-resistant bacteria in hospitals show the bugs are already adapting, he added.
Alcohol-based hand sanitizers, such as Pfizer Inc's Purell, caused less concern.
While one expert said data did not show they were better than plain soap, others said they do prevent the spread of germs. They also do not leave a residue that can trigger resistance.
Some doctors also worry antibacterial products can prevent children's immune system from properly developing by shielding them from bacteria needed to create natural resistance.
"This is still a controversial hypothesis," FDA's Rogers said.
Industry groups defended their antibacterial products as safe and necessary to protect consumers.
"The importance of controlling bacteria in the home is no different than in the professional setting," said Elizabeth Anderson, a lawyer for the Cosmetic, Toiletry and Fragrance Association. "We believe consumers should be assured that the products they are using are the most effective available."
The FDA has been sorting through the issue since 1972. Six years later it asked for more data on triclosan and again in 1994.
In the proposed rule issued more than a decade ago, the agency said such products were "practical for home use." It was not immediately clear when the agency would finalize its rule.
Bleach treatment neutralizes mold allergens
Treatment with household bleach reduces the allergy-inducing ability of mold spores, a new study shows.
Current efforts to remediate mold-contaminated buildings require replacement of contaminated materials, Dr. John W. Martyny of the National Jewish Medical and Research Center in Denver and colleagues note in the Journal of Allergy and Clinical immunology.
Also, the Environmental Protection Agency and many investigators argue that killing mold is not enough to reduce its allergenicity. Dilute sodium hypochlorite is known to kill mold, but it is not clear if it reduces mold's ability to produce allergic reactions.
Martyny and his team conducted the current study, funded by the Clorox Co., to determine if diluted bleach would destroy the ability of mold to produce an allergic response as well as kill the organism. Several studies, they point out, have found bleach can neutralize other types of household allergens, such as dust mite and cockroach proteins.
The researchers grew Aspergillus fumigatus on samples of three types of construction materials, as well as in solution. The samples and cultures were then treated with dilute bleach; Tilex, a cleaning product containing detergent and bleach; or water only.
The researchers then evaluated the number of spores using scanning electron microscopy and tested for viable mold. They also checked treated samples for antigens using ELISA and skin prick testing.
While bleach or Tilex treatment did not reduce the number of spores, surface allergens were no longer detectable in the treated samples. The surface of the spores treated with bleach or Tilex also showed changes in appearance. After adding bleach to the mold in aqueous solution, A. fumigatus allergens were no longer detectable by ELISA.
Skin prick tests found bleach treatment eliminated a response in five of eight mold-allergic individuals, while Tilex treatment inhibited response in seven of eight.
Some authorities on mold contamination, as well as some government agencies, recommend against treating fungi contaminated surfaces with bleach solutions, given the concern that substantial amounts of organic material may neutralize their disinfectant capacities, Martyny and colleagues note.
"On the basis of the results of our study, sodium hypochlorite-containing products should be reconsidered as one of the tools in the remediation of mold-contaminated buildings," the researchers conclude.
Roche Increasing Tamiflu Production
The manufacturer of a drug used to inhibit the effects of the bird flu virus will negotiate with generic drug companies to increase production, two U.S. senators announced Thursday.
Tamiflu is the most effective drug in treating bird flu.
Swiss-based Roche Holding AG will meet with four companies and maybe more in coming weeks, all in an effort to work out a licensing agreement that would allow other companies to produce Tamiflu, which is in great demand throughout the world.
"The bottleneck on Tamiflu has basically been broken," said Sen. Charles Schumer, D-N.Y., who announced the agreement along with Sen. Lindsey Graham, R-S.C.
The two senators met with George Abercrombie, head of Roche Pharmaceuticals in North America.
Generic manufacturers cannot legally sell the patented drug in the West and parts of Asia. Roche holds the patent, but it agreed to sub-license the production of Tamiflu to any company that can produce it in quantities large enough to help meet anticipated demand, Schumer said.
The determination of who gets the license will be made in cooperation with the U.S. government and other governments around the world, the senators said.
Health Tip: Stay Safe in Your Yard
Are you itching to get your yard in shape?
While the task may seem like child's play, some outdoor chores can be accidents waiting to happen.
St. John Ambulance Canada offers these safety tips:
Rake your lawn before you mow to ensure you've collected objects that could become projectiles under the mower blade.
Give your mower a tune up and perform a safety check before you start it.
Don't use electrical appliances in wet or damp areas.
Don't burn debris. There's always the risk of the fire getting out of control.
Health Tip: Blueberries Are Healthy
Blueberries are more than a tasty, decorative addition to a fruit plate.
One serving of blueberries contains a cup full of goodness, says Moses Taylor Hospital in Pennsylvania.
Here are the facts:
One cup of blueberries has 15 percent of your daily vitamin C requirement.
One cup contains 14 percent of required daily dietary fiber.
Blueberries have no cholesterol or fat.
They are low in calories.
Water has no calories, vitamins or minerals, but drinking plenty of it it can reduce your risk of disease. Drinking more than six glasses of water each day cuts the risk of developing bladder cancer in half. Some evidence suggests that staying well hydrated cuts the risk of colon and breast cancer, and lessens your chances of developing kidney stones -- even if you've already passed one or more. Women should aim for about nine cups of fluids daily. Men should shoot for 12 cups.
Fitness Tip of the day:
Lose 5 lbs. a year without dieting.
One simple change in your daily routine can help you burn extra calories and shed excess pounds. Anything you do every day to burn an extra 50 calories will save you the equivalent of five extra pounds over the course of a year. It can be as easy as parking your car a mere five minutes further from your office each morning and then walk briskly to your desk and back again after work. That's easy weight loss in just 10 minutes a day!
FAQ of the day:
Should I throw out my saltshaker?
If you're concerned about sodium, your saltshaker isn't your biggest concern. For starters, eat fewer processed foods, which tend to be high in salt, and more fruits and vegetables. But typically, rather than limiting sodium, blood pressure control depends more on maintaining a healthy weight and getting enough calcium, potassium (found in all fruits and vegetables) and magnesium (in green vegetables, whole grains and nuts). In the large DASH (Dietary Approaches to Stop Hypertension) study, more than 600 volunteers who ate 10 servings of fruits and vegetables a day, along with three servings of calcium-rich low-fat dairy foods, significantly reduced blood pressure across all age groups and ethnicities.