Breast Cancer Tumor Test to Tailor Treatments

Breast cancer is the second most common cancer in U.S. women (after skin cancer). Many women with early-stage breast cancer are advised to receive chemotherapy in addition to radiation and hormonal therapy. However, it isn’t necessary to treat all breast cancer with chemotherapy, which can also be costly, toxic, and inconvenient.

The death rate from breast cancer has dropped steadily over the past 20 years, but breast cancer is still the second leading cause of cancer-related death in U.S. women. Image Credit: Ryan McVay/Photodisc/Thinkstock.

An international team of researchers has been exploring ways to identify which tumors would be the most likely to benefit from chemotherapy. From April 2006 to October 2010, the scientists enrolled more than 10,000 women from around the world in a large clinical trial sponsored by NIH’s National Cancer Institute (NCI).The women, ages 18 to 75, had recently been diagnosed with a specific type of breast cancer: hormone-receptor positive, human epidermal growth factor receptor type 2 (HER2) negative that hadn’t spread to the lymph nodes.

Many women with this type of breast cancer can likely be adequately treated with hormone therapy alone. However, it’s been difficult to identify the women who could safely avoid adjuvant chemotherapy, which is given after the primary therapy to reduce the risk of metastases and thus increase the chance of long-term cancer-free survival.

The scientists explored the ability of a diagnostic gene test, the Oncotype DX Recurrence Score (Genomic Health, Inc.), to predict which women could safely avoid receiving chemotherapy. The test had previously been found, using retrospective analyses (which look back at past events), to help predict the usefulness of chemotherapy and the likelihood of distant breast cancer recurrence. The test works by analyzing RNA from tumor samples for the presence of 21 genes. Based on the results, tumors are graded on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence.

This prospective study (looking forward, following the women over time) was led by Dr. Joseph A. Sparano of Montefiore Einstein Center for Cancer Care and Albert Einstein College of Medicine. Results were published online on September 28, 2015, in the New England Journal of Medicine.

The team found that 1,626 of the women (16%) had a recurrence score of 0 to 10, indicating a very low risk of recurrence. These women were assigned to receive standard hormone therapy such as tamoxifen or aromatase inhibitors, but didn’t undergo chemotherapy. At 5 years of follow-up, their risk of recurrence of breast cancer at a distant site was less than 1%, and the risk of any recurrence was less than 2%. The women had an overall survival rate of 98%.

These results show that the Oncotype DX test can clearly identify women with an early stage of this type of breast cancer who can safely avoid chemotherapy. However, nearly 70% of the participants had a mid-range score of 11 to 25. These women were randomly assigned to receive endocrine therapy plus chemotherapy or endocrine therapy alone, and are still being monitored. Scientists continue to work on other diagnostic gene test as well.

—by Carol Torgan, Ph.D.

Every Thing You Need to Know About ADHD

Is your child in constant motion? Does he or she talk incessantly? Or have trouble focusing and prefer to daydream?

Then your child may have attention deficit hyperactivity disorder, or ADHD.

This disorder often begins between the ages of 3 and 6 years, according to the National Institute of Mental Health (NIMH). And it’s not just a childhood disease: ADHD may continue through the teenage years and into adulthood (see sidebar). According to the Centers for Disease Control and Prevention (CDC), approximately 11% of children 4-17 years of age (6.4 million) have been diagnosed with ADHD as of 2011.

Three types of ADHD are recognized:

• inattentive (trouble focusing, following instructions, and finishing tasks)
• hyperactive-impulsive (constantly on the go, talking excessively, and interrupting others)
• combined (symptoms of both inattention and hyperactivity-impulsivity)

Diagnosing the Disorder

Studies show that the number of children being diagnosed with ADHD continues to increase, from 7.8% in 2003 to 11.0% in 2011, according to the CDC. Tiffany R. Farchione, M.D., a child psychiatrist at FDA, reviews drugs to treat ADHD. She explains that the increase may be due to a greater public awareness of the disorder and psychiatric illnesses in general.

Boys (13.2%) were more likely than girls (5.6%) to have ever been diagnosed with the disorder. In addition, boys are more likely to have the hyperactive-impulsive type, which is easier to spot than the quieter child who is inattentive, says Farchione.

If you suspect your child might have ADHD, see your family doctor or pediatrician, suggests Farchione. Your child’s vision, hearing, and anything else that may contribute to inattention should also be checked. The doctor may

Treatments

FDA has approved two types of medications—stimulants and non-stimulants—to help reduce the symptoms of ADHD and improve functioning in children as young as 6 years.

It may seem counterintuitive, Farchione says, but despite their name, stimulants, which contain various forms of methylphenidate and amphetamine, actually have a calming effect on hyperactive children with ADHD. They are believed to increase brain levels of dopamine—a neurotransmitter associated with motivation, attention, and movement.

FDA has also approved three non-stimulants to treat the symptoms of ADHD: Strattera (atomoxetine), Intuniv (guanfacine), and Kapvay (clonidine). These provide a useful alternative for children who do not tolerate stimulants well. Talk with your healthcare professional about what medications may be best for your child.

In addition to medication, some children with ADHD receive behavioral therapy to help manage symptoms and provide added coping skills. Moreover, concerned parents can reach out to their children’s schools and community support groups for information and guidance on how to cope with ADHD behavior. “It’s helpful to engage with the different individuals who are involved in a child’s life when managing the disorder,” Farchione says.

Testing the Effects of Medication in Younger Children

FDA-approved medications currently on the market have been tested for safety and effectiveness in clinical trials of children ages 6 and above. But once a drug has been approved and is on the market, FDA is now asking for clinical trials with participants of children as young as 4 and 5, Farchione says.

“This is a fairly new policy,” she adds. “We know ADHD medications are being prescribed for younger children, and we think it’s essential that the data from clinical studies reflect the safety and effectiveness for this age group.”

Consequences of Not Treating

Left untreated, ADHD can have serious consequences.

A child may fall behind in school, encounter difficulties in friendships, and have conflicts with parents, says the American Academy of Child and Adolescent Psychiatry.

Studies show that children with untreated ADHD have more emergency room visits and are more likely to have self-inflicted injuries than those treated for the disorder. Untreated adolescents with ADHD are more likely to take risks, such as drinking and driving. And they have twice as many motor vehicle accidents as those who are treated.

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ADHD: Not Just for Kids

Studies suggest that approximately 4% of adults may have attention deficit hyperactivity disorder (ADHD). The symptoms of ADHD in adults are the same as those in children, but they manifest somewhat differently. Adults with ADHD may have poor time management skills and trouble with multitasking, become restless with downtime, and avoid activities that require sustained concentration.

A diagnosis of ADHD in an adult is given only when it’s known that some of the symptoms were present early in childhood, usually under the age of seven.

“For some adults, a diagnosis of ADHD can bring a sense of relief,” says psychiatrist Tiffany Farchione. Receiving a diagnosis allows adults to understand the reasons for their problems, and treatment can help them to deal with challenges more effectively

Cold, Flu, or Allergy? Know the Difference for Best Treatment

Cold, Flu, or Allergy?

Know the Difference for Best Treatment

You’re feeling pretty lousy.You've got sniffles, sneezing, and a sore throat. Is it a cold, flu, or allergies? It can be hard to tell them apart because they share so many symptoms. But understanding the differences will help you choose the best treatment.

“If you know what you have, you won’t take medications that you don’t need, that aren’t effective, or that might even make your symptoms worse,” says NIH’s Dr. Teresa Hauguel, an expert on infectious diseases that affect breathing.

Cold, flu, and allergy all affect your respiratory system, which can make it hard to breathe. Each condition has key symptoms that set them apart.

Colds and flu are caused by different viruses. “As a rule of thumb, the symptoms associated with the flu are more severe,” says Hauguel. Both illnesses can lead to a runny, stuffy nose; congestion; cough; and sore throat. But the flu can also cause high fever that lasts for 3-4 days, along with a headache, fatigue, and general aches and pain. These symptoms are less common when you have a cold.

“Allergies are a little different, because they aren’t caused by a virus,” Hauguel explains. “Instead, it’s your body’s immune system reacting to a trigger, or allergen, which is something you’re allergic to.” If you have allergies and breathe in things like pollen or pet dander, the immune cells in your nose and airways may overreact to these harmless substances. Your delicate respiratory tissues may then swell, and your nose may become stuffed up or runny.

“Allergies can also cause itchy, watery eyes, which you don’t normally have with a cold or flu,” Hauguel adds.

Allergy symptoms usually last as long as you’re exposed to the allergen, which may be about 6 weeks during pollen seasons in the spring, summer, or fall. Colds and flu rarely last beyond 2 weeks.

Most people with a cold or flu recover on their own without medical care. But check with a health care provider if symptoms last beyond 10 days or if symptoms aren’t relieved by over-the-counter medicines. For more about when to see a doctor, go to CDC's Flu Page .

To treat colds or flu, get plenty of rest and drink lots of fluids. If you have the flu, pain relievers such as aspirin, acetaminophen, or ibuprofen can reduce fever or aches. Allergies can be treated with antihistamines or decongestants. See the “Wise Choices” box for more details.

Be careful to avoid “drug overlap” when taking medicines that list 2 or more active ingredients on the label. For example, if you take 2 different drugs that contain acetaminophen—one for a stuffy nose and the other for headache—you may be getting too much acetaminophen.

“Read medicine labels carefully—the warnings, side effects, dosages. If you have questions, talk to your doctor or pharmacist, especially if you have children who are sick,” Hauguel says. “You don’t want to overmedicate, and you don’t want to risk taking a medication that may interact with another.”

Cold, Flu, or Allergy? Tips and Treatments

Symptoms	Cold	Flu	Airborne Allergy
Fever	Rare	Usual, high (100-102 °F), sometimes higher, especially in young children); lasts 3-4 days	Never
Headache	Uncommon	Common	Uncommon
General Aches, Pains	Slight	Usual; often severe	Never
Fatigue, Weakness	Sometimes	Usual, can last up to 3 weeks	Sometimes
Extreme Exhaustion	Never	Usual, at the beginning of the illness	Never
Stuffy, Runny Nose	Common	Sometimes	Common
Sneezing	Usual	Sometimes	Usual
Sore Throat	Common	Sometimes	Sometimes
Cough	Common	Common, can become severe	Sometimes
Chest Discomfort	Mild to moderate	Common	Rare, except for those with allergic asthma
Treatment	Get plenty of rest. Stay hydrated. (Drink plenty of fluids.) Decongestants Aspirin, acetaminophen, or ibuprofen for aches and pains	Get plenty of rest. Stay hydrated. Aspirin, acetaminophen, or ibuprofen for aches, pains, and fever Antiviral medicines (see your doctor)	Avoid allergens (things that you’re allergic to) Antihistamines Nasal steroids Decongestants
Prevention	Wash your hands often. Avoid close contact with anyone who has a cold.	Get the flu vaccine each year. Wash your hands often. Avoid close contact with anyone who has the flu.	Avoid allergens, such as pollen, house dust mites, mold, pet dander, cockroaches.
Complications	Sinus infection middle ear infection, asthma	Bronchitis, pneumonia; can be life-threatening	Sinus infection, middle ear infection, asthma

Psoriasis Treatments Are Getting More Personalized

The more scientists learn about psoriasis, the more therapeutic options are becoming available for patients with this skin disease.

“As we better understand the disease, researchers know more about what specific factors to target in order to develop effective treatments,” says Melinda L. McCord, M.D., a dermatologist at the Food and Drug Administration.

The treatment for psoriasis has changed from the previous gradual step-by-step approach. Today, doctors seek to optimize treatment from the first visit—whether with phototherapy or systemic therapies—based on the specific needs of each patient.

“Tomorrow’s treatments will become even more personalized because the drugs in development now are targeting different aspects of the immune system,” McCord notes.

Psoriasis is an immune system disorder characterized by inflammation and the rapid overproduction of skin cells, creating scaling, pain, swelling, heat and redness. About 7.5 million Americans have psoriasis, a skin condition that can create significant physical and emotional discomfort.

Therapies for psoriasis include:

• Medicines applied to the skin (topical treatment)
• Light treatment (phototherapy)
• Drugs taken by mouth or injection (systemic therapy)

There is no cure for psoriasis, so the main goals of treatment are to reduce inflammation and to stop the skin cells from growing so quickly.

In the past, doctors treated psoriasis using a “step-wise approach.” Patients with mild to moderate psoriasis would start with topical therapies and, if they did not respond well to that, move on to other treatments, such as systemic therapy or phototherapy. This approach called for treating people with moderate to severe psoriasis with phototherapy or traditional systemic therapies—drugs such as methotrexate and cyclosporine—before offering them biologic therapies (a type of treatment that works with your immune system).

That strategy has changed to a more patient-specific approach. Today, patients and their doctors can choose a treatment based on its effectiveness, the severity of their disease, lifestyle considerations, risk factors, and associated diseases (co-morbidities).

The most recent biologic product approved by the FDA for the treatment of psoriasis is Stelara (ustekinumab). Ustekinumab contains an antibody that’s produced in a laboratory and designed to bind to a specific target in the immune system. “When given to patients, this antibody blocks the action of two proteins (interleukin 12 and 23) that contribute to the inflammation and the overproduction of skin cells. By targeting these proteins, ustekinumab can interrupt the inflammatory pathway,” McCord says.

“Looking forward, the drugs in development are targeting different pathways in the immune system that lead to inflammation. Researchers are exploring the importance of interleukin 17,” McCord says. “They’re also looking at proteins and molecules that can interrupt cellular signaling, which can increase the spreading of the inflammation.”

“As we learn more about the immune pathways that lead to the development of psoriasis, we can target specific molecules for treatment and make more therapeutic options available to patients,” McCord says. “Understanding the disease gives us the opportunity to target specific factors.”

McCord recommends a team approach to treating psoriasis. Patients, families and their health care providers need to work together to address the multiple diseases that may occur in association with psoriasis, including the risk of developing metabolic syndrome (the occurrence of obesity, high blood pressure, high cholesterol and diabetes in one patient), lymphoma, heart disease and/or depression. “We do not completely understand the relationship of these co-morbidities to psoriasis, but it is an area of active research,” she adds.

Because psoriasis is a chronic disease with no cure, patients may need to use treatments for a long time. Many therapies approved by FDA have been evaluated for extended time periods.

Psoriasis has environmental and genetic components. It is more common in adults and can run in families. What triggers it? A virus? Bacteria? Stress? Other environmental factors? “We just don’t know,” McCord says.

The good news is that patients can treat some of the signs and symptoms of psoriasis with simple measures. For example, regular use of moisturizers may improve the itching and scaling. Reducing or limiting tobacco use and alcohol consumption may decrease the number of flares of psoriasis. Lifestyle changes—such as maintaining a healthy weight and being physically active—may help lessen or prevent the development of associated diseases.

McCord advises patients to seek treatment early from a doctor experienced with the disease. A dermatologist can provide patients with the correct diagnosis and information to manage the disease. “If you are diagnosed and treated early, you may avoid the pitfalls of ineffective and inappropriate therapy,” she adds.

Some patients become easily discouraged about treatments, but newer therapies may make them more comfortable. That’s why McCord says patients should investigate treatment options early and educate themselves about their condition. Even if patients have a mild case of psoriasis and decide they don’t want a particular treatment option, there are ways they can decrease their symptoms.

“Psoriasis has a great emotional impact on some patients. But it doesn't have to, given the right care and treatment,” she says.

Topical Acne Products Can Cause Dangerous Side Effects

Certain acne treatments can, in rare instances, cause severe allergic reactions that are potentially life-threatening.

The Food and Drug Administration (FDA) is warning that the use of certain acne products containing the active ingredients benzoyl peroxide or salicylic acid can cause rare but serious and potentially life-threatening allergic reactions or severe irritation. An active ingredient is the component that makes the medicine effective against the illness or condition it is treating.

The acne products the FDA is warning about are sold over-the-counter (OTC) and applied to the skin (topical). Their serious allergic reactions differ from the less harmful irritations already included in the product Drug Facts labels, which include burning, dryness, itching, peeling, redness, and slight swelling where the product is applied.

“There is currently no mention of the possibility of these very severe allergic reactions on the product labels,” says Mona Khurana, M.D., a medical officer at FDA. “It’s important that consumers know about them, and that they know what to do if they occur.”

Consumers can find out if an OTC topical acne product contains benzoyl peroxide or salicylic acid by looking at the Active Ingredient(s) section of the Drug Facts label on the product package.

FDA has issued a Drug Safety Communication (DSC) to inform both consumers and health care professionals of the potential dangers of these products.

Products of concern are marketed under different brand names such as Proactiv, Neutrogena, MaxClarity, Oxy, Ambi, Aveeno, and Clean & Clear. They are available as gels, lotions, face washes, solutions, cleansing pads, toners and face scrubs.

From 1969 through January 28, 2013, FDA received 131 reports from both consumers and manufacturers of allergic and hypersensitivity-related adverse reactions associated with these products. About 42% of these reactions occurred within minutes to 24 hours of use. The affected persons ranged in age from 11 to 78 years.

Types of Reactions

Forty percent of these reports described severe allergy symptoms such as throat tightness, shortness of breath, wheezing, low blood pressure, fainting or collapse. Isolated instances of hives, itching of face or body (even of parts of the body where the person did not apply the medication), and swelling of eyes, face and lips were also reported.

Based on the information reported, FDA cannot determine if these reactions were triggered by the products’ active ingredients, the inactive ingredients, or a combination of both.

While no deaths have been reported, 44% of the cases required hospitalization.

“FDA will continue to monitor closely and evaluate this safety issue,” Khurana says. The agency is also encouraging manufacturers to use the drug label to advise consumers how to test the product’s safety before using it for the first time.

For example, Khurana suggests that new users should apply a small amount of the product to a small affected area for three days. If no discomfort occurs, they can follow the labeled directions for normal use.

What to Do If a Bad Reaction Occurs

She adds that there are a number of important safety actions to counter an allergic reaction, including:

• Avoid using the product if you’ve had previous allergic or hypersensitivity reactions.
• Stop using the product if you develop hives or itching of the face or body.
• Stop using the product and seek immediate medical attention if you develop throat tightness or swelling of the eyes, face, lips or tongue; feel faint; or have difficulty breathing.

FDA encourages consumers to report any negative reactions or side effects from use of these products to the FDA’s MedWatch program.

Hemophilia Treatments Have Come a Long Way

With appropriate medical care, people with hemophilia are living healthier lives.

Gone are the days when a hemophilia diagnosis meant you could not live a normal life. Now more treatments are approved by the Food and Drug Administration (FDA), and people with the condition can better manage bleeding. That’s good news as thousands observe World Hemophilia Day on April 17, 2014.

Hemophilia is a rare bleeding disorder. It is usually hereditary, but it can be acquired in rare cases if a person’s body develops antibodies that attack clotting factors in the bloodstream. Hereditary hemophilia usually occurs in males and currently affects about 23,500 Americans.

People with hemophilia are lacking one or more important clotting factors, which are proteins needed for blood clotting. Several types of clotting factors exist and there are two main types of hemophilia, says Nisha Jain, M.D., chief of the Clinical Review Branch in FDA’s Office of Blood Research and Review. Hemophilia A occurs when people have low levels, or missing, clotting factor VIII (8). Hemophilia B occurs when people have low, or missing, clotting factor IX (9).

People with hemophilia may bleed for a longer time than others after injury or surgery. They may also have internal bleeding—especially in knees, ankles, and elbows—that can damage organs and tissues and even be life-threatening.

Now the primary type of hemophilia treatment is replacement therapy: Concentrates of clotting factor VIII (for hemophilia A) or clotting factor IX (for hemophilia B) are injected into a patient’s vein to replace low or missing factor.

These concentrates have traditionally been made from human blood. Today, an increasing number are made using recombinant DNA technology (a form of artificial DNA), with some made without any material sourced from humans or animals. The final product is a powder that is mixed with sterile water before use.

Some people have regular preventive or “prophylactic” therapy to prevent bleeding. This can be done in less than five minutes, excluding prep time, Jain explains. Others have therapy only as needed.

The type and frequency of treatment varies depending on the severity of hemophilia, which can be classified as mild, moderate or severe.

People with mild hemophilia have 6% to 49% of the normal levels of clotting factors in their blood. They generally only have bleeding problems after serious injury or surgery.

Those with moderate hemophilia—about 15 percent of the hemophilia population, according to the
National Hemophilia Foundation—have 1% to 5% of normal clotting factor levels. They can have bleeding problems after injury and spontaneously.

Those with severe hemophilia—about 60% of the hemophilia population, per NHF—have less than 1% of normal clotting factor levels. They bleed after injury and may have frequent spontaneous bleeding, including bleeds into joints and muscles. In addition to factor replacement, pain medication and physical therapy are also used to lessen pain and swelling if joint bleeds occur.

“The mild patients rarely need treatment. And moderate patients are the same,” explains Jain. In certain situations, such as before dental work, patients with mild hemophilia receive Desmopressin (DDAVP) a man-made hormone that increases the level of factor in the blood. “Patients with severe hemophilia are those who really need treatment to prevent or resolve bleeds.”

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A Shift Toward Prevention

Doctors, particularly hematologists who specialize in the study of blood, tend to identify people with severe hemophilia early. “Patients can be diagnosed as infants during circumcision,” says Jain. Then families can work with hematologists and hematology treatment centers.

“In recent times, we have seen shifting toward the prevention of bleeds,” Jain says. “You want to prevent bleeding that causes joint damage. Once joint damage starts, it is difficult to stop progression unless bleeding into joints is reduced.”

The treatments for hemophilia continue to improve, and FDA has approved many replacement factors in recent years. For instance, in March 2014 it approved Alprolix, the first Hemophilia B treatment designed to require less frequent injections when used to prevent or reduce the frequency of bleeding. It also recently approved Rixubis—a factor IX product—to control, prevent and reduce bleeding associated with hemophilia B. And the agency approved Novoeight, a factor VIII product, for control of bleeding and a routine prophylaxis treatment for adults, adolescents and children with hemophilia A.

Of course, the agency continues to carry out its broad responsibility to regulate medicines made from blood and blood components, including clotting factors. Today, due to strengthened FDA safeguards and oversight, these products are safer than they have ever been.

“Patients should stay informed about various treatment options,” Jain adds, “and should consult with their health care providers to obtain, and follow, a comprehensive management plan.”

She says those with hemophilia tend to be well-educated about their health and notes, “With appropriate treatment and care, people with hemophilia can, and do, live normal lives.”