Category Archives: General Treatment Issues

Dietary Supplements Before and During Chemotherapy

Meg Seymour, PhD, National Center for Health Research


Many Americans, including those with cancer, take dietary supplements. People take supplements because they believe it will help them stay healthy and give them vitamins and minerals they may not get from their diet. Chemotherapy patients often take supplements because their nausea makes it difficult to eat, and they want to be sure to get enough nutrients. 

People think of dietary supplements as a no-risk insurance policy to improve nutrition, but a study published in 2020 shows that supplements can have risks if you are undergoing chemotherapy. More than 1,000 breast cancer patients were asked whether or not they took any supplements either before or during their chemotherapy.[1] The researchers then continued to evaluate any subsequent cancer or death for up to 15 years (almost all of the women were followed for at least 5 years).

Results showed that patients who took vitamin B12 both before and during their chemotherapy were more likely to develop cancer again in the 5-15 years after treatment and were more likely to die as a result. They were also more likely to die from any cause, not just from cancer. This increase in subsequent cancer or death was only for people who took the supplements both before and during their chemotherapy. Patients who only took the supplements before chemotherapy or only took supplements during chemotherapy were not more likely to develop cancer again or to die from cancer or other causes in the years after treatment. Patients who took iron supplements both before and during chemotherapy were also more likely to develop cancer again after treatment or to die of cancer or any cause. However, the same was also true for people who only took iron supplements during their chemotherapy.  

Results showed that patients who took vitamin B12 before and during their chemotherapy were more likely to die or have their cancer return. They were also more likely to die from any cause, not just from cancer. This increase in cancer recurrence or death was only for people who took the B12 supplements both before and during their chemotherapy. Patients who only took the B12 supplements before chemotherapy or only took supplements during chemotherapy were not more likely to have a recurrence of their cancer or die. Patients who took Iron supplements both before and during chemotherapy were also more likely to have their cancer return or to die of any cause. However, the same was also true for people who only took Iron supplements during their chemotherapy.

The researchers also looked at antioxidant supplements, which include vitamins A, C, and E. They found that patients taking these supplements both before and during chemotherapy had a 41% higher chance of cancer returning after treatment. However, this finding was not “statistically significant,” which means that more research is needed to determine whether these worse outcomes occurred by chance. The 44% of the patients in the study who were taking multivitamins did not have better or worse outcomes than people who were not taking them. 

This is what scientists call an observational study rather than a clinical trial. In a clinical trial, some patients would be randomly assigned to take supplements and others would be assigned to take a placebo (with no active ingredients). In an observational study, people make their own decisions about what treatment (in this case supplements) to take. Those who chose to take supplements might have different health issues or health habits than those who did not. For example, it is possible that the people who were more likely to take supplements both before and during their chemotherapy were less healthy to begin with. For example, they could have been taking B12 or Iron supplements because they had anemia, and anemia may have increased the possibility of cancer recurrence or death. Also, because patients were asked whether or not they took supplements (instead of being given the supplements by researchers), it is impossible to know whether what patients said about supplements was completely accurate. For example, some patients could have said that they were regularly taking a supplement, but really they only took it occasionally.   

Dr. Christine Ambrosone, the lead researcher of the study, said in an interview that this is only one observational study, and doctors should not necessarily base their recommendations on this single study. Doctors need to consider the specific needs of each patient. For example, someone with anemia might need a dietary supplement, and the benefits of those supplements might outweigh the potential risks. 

If you are considering taking a dietary supplement, it is important to keep in mind that the Food and Drug Administration does not regulate dietary supplements for purity and quality. There is no guarantee that a supplement will work or even that it contains exactly what the bottle says it contains.[2] It is always important to talk with your doctor to help you decide if the benefits of any dietary supplement you are considering outweigh the potential risks. 

 

  1. Ambrosone, C. B., Zirpoli, G. R., Hutson, A. D., McCann, W. E., McCann, S. E., Barlow, W. E., … & Unger, J. M. (2019). Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). Journal of Clinical Oncology, JCO-19.
  2. Brooks, J, Mitchell, J., Nagelin-Anderson, E. , & Zuckerman, D. National Center for Health Research. How Safe are Natural Supplements? Center4research.org. http://www.center4research.org/examining-safety-natural-supplements/. 2019.

What People With Cancer Need to Know about Coronavirus (COVID-19)

Diana Zuckerman, Ph.D., Cancer Prevention and Treatment Fund: updated February 10, 2021.

The coronavirus can infect anyone, young or old, healthy or frail.  But, people diagnosed with cancer during the last year are at higher risk of dying from COVID-19 if they are infected. Here’s what you need to know.

People who are over 60 or who have cancer and other serious health conditions, and their loved ones, need to be especially careful to avoid getting infected.  A study published in December 2020 of more than 2 million cancer patients, found that people diagnosed with cancer during the previous year are much more likely to die of COVID compared to other COVID patients.  All cancer patients were at higher risk, but the ones in most danger had been diagnosed with leukemia, non-Hodgkin’s lymphoma, or lung cancer. The CDC has also updated their list of other health problems that put people at greatest risk, and they include many common health conditions: Anyone who is obese (BMI of 30 or higher) or has a serious heart condition, Type 2 diabetes, a weakened immune system (from cancer or an organ transplant), chronic kidney disease, COPD, or sickle cell disease is especially at risk if they are exposed to the coronavirus.  Smoking also increases the risk of being seriously harmed by the virus, as do many other medical conditions, including high blood pressure, pregnancy, HIV, and liver disease.

If you had scheduled medical appointments, surgery, screening, or other procedures in the past year that were considered not urgent or not immediately life-threatening, those were probably postponed. This was for everyone’s protection.  Many hospital staff, including doctors, nurses, receptionists, and cleaning staff, have been vaccinated against COVID but their facilities may be limiting procedures that are not essential because the doctors are vaccinating others or are treating COVID patients. You don’t want to be exposed to the coronavirus when you go in for surgery or testing procedures for other medical conditions.  And, you don’t want your medical center to be less able to fight the coronavirus at a time when it is spreading throughout your community.

Will the COVID vaccines make it safer to have medical procedures or doctor’s appointments? To visit friends and family members?

Many healthcare workers have been vaccinated, but some nurses and aides have refused the vaccine so far.  You should ask about that when you make an appointment. Pregnant healthcare workers and those with serious allergies may choose not to be vaccinated. Pregnant healthcare workers and those with serious allergies may choose not to be vaccinated.  More important, the vaccines do not prevent infection, even though they usually prevent people from getting obviously sick.  If your healthcare worker is vaccinated, he or she could have asymptomatic COVID without knowing it, and could possibly infect others.  For that reason, healthcare workers and patients need to continue to wear masks and keep their distance.

The coronavirus is still spreading in all 50 states, in urban, suburban, and rural areas, so it is important to listen to health experts who tell you to stay home, limit contact with others, wear a mask, and keep a distance of 6 feet away when you or your family members or caregivers go grocery shopping or other essential activities. It will be months before most people are vaccinated.  Unfortunately, some governors, mayors, and state legislators have reopened businesses for political reasons, even in states where the virus is spiking.  Even if you are staying at home as much as possible, the fact that others in your community are going to bars, parties, restaurants, stores, and hair salons will put you at greater risk when you make essential visits to the supermarket, to work, to the doctor, or spend time outdoors, because you may come into contact with people who are infected because they aren’t being as careful as you are.

What is coronavirus?

Coronaviruses are a large group of viruses that can cause respiratory illness. The new (novel) coronavirus is called SARS-CoV-2 and the illness it causes is called coronavirus disease 2019, which is why it’s abbreviated as COVID-19.

How does COVID-19 spread between people?

The virus usually spreads through close contact with other people, especially through invisible or very tiny droplets when a person coughs, sneezes, sings, exercises – or even when they breathe or talk normally. These droplets can travel through the air and can be inhaled or get into the noses, mouths, or eyes of people nearby.

The virus is thought to be most contagious in the days just before and just after a person develops symptoms, but it is possible to catch the virus from infected people who have no symptoms at all.  Experts still don’t know how contagious the virus is when a person has it but never develops symptoms.  This is crucial information that scientists are trying to find out, especially since experts believe that many young children never develop symptoms, while other children get very sick and some have died from the coronavirus.

What about children?  Unlike the flu, which is riskiest for the youngest children and oldest adults, infants and young children are much less likely to get sick from the coronavirus than adults.  Preliminary studies suggest that children over 10 are as contagious as adults, but that younger children are much less infectious. For example, there are few known examples of the virus spreading in daycare centers that follow coronavirus safety standards. Nevertheless, almost half a million children have been diagnosed with the virus in the U.S. (almost 10% of all cases) and 70,000 children were newly diagnosed in late August, which was 17% more than the weekly number of new cases two weeks earlier.  Fortunately, few children become so sick that they are hospitalized (estimates range from less than 1% to 8.5%), and less than half of 1% of children diagnosed with coronavirus in the U.S. have died.

The tiny droplets from coughing, sneezing, singing, talking, or breathing (as well as fecal matter containing the virus) can result in the virus on surfaces where it can survive for hours or even days. When you touch these surfaces and then touch your face, you can be exposed to the virus. However, there are no documented cases of anyone catching COVID from a surface.  Nevertheless, it’s important to wash your hands regularly.  If you’re concerned about exposure at home, you can wipe down surfaces in your bathroom, kitchen, and other rooms with bleach or rubbing alcohol to help prevent exposure.

What about food or food packaging?  The risk of catching the virus from packaging is extremely low, but it’s a good idea to wash your hands for at least 20 seconds after handling mail, takeout containers, and packaging from groceries. You don’t need to disinfect food packages using a cleaning product that kills viruses, and NEVER use bleach or disinfectants on fruit, vegetables, or any other food.

What about the vaccines?

If you are eligible to be vaccinated with either the Pfizer or Moderna vaccine, that is the best protection available for most people.  Keep in mind, however, that the vaccines were not studied on nursing home patients and not studied on many people with COVID who were ages 65 or older, so it might be less effective for older people.  (Flu vaccines are often less effective for older people, because their immune systems are weaker).  The vaccines were found to be as safe for adults of all ages and races. The vaccines were  studied on few people under 18, pregnant women, people with compromised immune systems, or those with serious allergies, so it will be a while before we have information about safety or effectiveness data for them.

Both of the vaccines have frequent side effects such as fatigue and chills, especially after the second dose.  These are not considered dangerous, but it is important that anyone getting vaccinated is told about those risks, since they could be frightening to patients who don’t understand that those symptoms are not thought to be reason for concern.

What are the symptoms of COVID-19?

Symptoms tend to start between 2 and 14 days after coming into contact with the virus.  Although some people have compared the symptoms to a cold or flu, not everyone with COVID-19 has those types of symptoms.  In fact, some people (especially children, teens, and younger adults) have very mild symptoms or none at all, which is why getting tested is so important before you spend time with others. The CDC says that people with these symptoms or combination of symptoms may have COVID-19:

  • Cough
  • Shortness of breath or difficulty breathing

Or at least two of these symptoms:

  • Fever
  • Repeated shaking with chills
  • Muscle pain
  • Headache
  • Sore throat
  • New loss of taste or smell
  • Congestion or runny nose
  • Nausea or vomiting
  • Diarrhea

Those are the most common symptoms.  However, children or adults can have other symptoms as well, including heart problems and “covid toes” that look like a minor case of frostbite.

Most people who are infected with this coronavirus have mild symptoms and can recover at home in about 2 weeks. However, symptoms can become severe.  These are the ones that require immediate medical attention:

  • difficulty breathing or shortness of breath
  • persistent chest pain or pressure
  • confusion or inability to awaken
  • blueish color in the lips or face

As described above, people who are older than 60 or with other medical conditions are more likely to develop severe illness and complications from COVID-19. The most serious complications include pneumonia, stroke, blood clots, organ failure, and death.

How else can I protect myself and others?

If you are not yet eligible to be vaccinated, the best way to protect yourself is to avoid being exposed to the virus. There are no proven cures, so don’t be fooled by claims, regardless of the source.  Two types of medications have been found to help people who are seriously ill, but are not a cure.  Remdesivir has been found to help very ill patients by reducing the number of days of hospitalization in one study, but was not effective in a WHO study published in October.  It has not been proven to save lives. Two inexpensive steroids, dexamethasone and hydrocortisone, have been found to reduce the chances of dying among COVID-19 patients on ventilators or those requiring oxygen, but not other patients. Regeneron, the experimental antibody drug that President Trump took when he was diagnosed, is not generally available but has been used with good results by some friends of the President.  However, it was found to have a potential safety concern and as of October 30 is no longer being administered experimentally to hospitalized patients receiving mechanical ventilation of intense oxygen.  It is still being studied on less seriously ill COVID-19 patients.

Experts now agree that hydroxychloroquine with or without azithromycin is not a good treatment for COVID-19 because it has been found to increase heart problems and has not been shown to prevent or treat COVID-19.  Another possible treatment is blood plasma from people who recovered from COVID-19.  Research has shown these transfusions are usually safe, but there is no clear evidence that they are beneficial.

Research is continuing to find out which of these treatments are safe and effective and for which patients.

“Social distancing” or “physical distancing” refers to staying away from other people because it is impossible to know who has the virus.  The safest people in your life are the ones you are living with who are not exposed to others who might have the virus (in other words, they are not going to work or spending time close to other people). Staying at home and not seeing your friends and loved ones is not fun, but it is essential for your own safety and for everyone else’s.  If everyone does that now, the spread of this virus will be reduced sooner, and some of these restrictions will no longer be necessary in a few weeks.

Spending time with friends, family, or people at work

In general, the more people you interact with, the more closely you interact with them, and the longer that interaction, the greater your chances of becoming infected or infecting othersThat’s why there have been so many cases after Thanksgiving, and why hospitals are full all over the country. So, think about:

  • How many people will you interact with?  (The fewer the better)
  • Can you keep 6 feet of space between you and others?
  • Will you be outdoors or indoors? (Outdoors is somewhat safer. It can be heated but not if it has walls all around and a ceiling.)
  • What’s the length of time that you will be interacting with people? (Shorter is better)

Research conclusively shows that face masks that cover your mouth and nose help to prevent the spread of the coronavirus.  Some masks are more effective than others:  stretchy “gators” may actually do more harm than good, and bandanas and scarves are too loose to be very helpful.  The paper surgical masks worn in hospitals are effective and so are cloth masks you can make for yourself or buy, if they are made of cotton and at least two layers thick. Masks are important to prevent people from spreading the virus and also to help helps prevent infection or serious symptoms for the person wearing the masks. Experts suggest wearing two masks at the same time for extra protection.

Bottom line: Since most of us haven’t been vaccinated and can’t get coronavirus tests every day, it’s especially important to wear masks whenever you are out in public or with people you don’t live with.  But you should NOT be out in public or with people you don’t live with except when it’s essential.  Depending on your age, health, and who you spend time with, it may not be safe for you to go to all the places that are open.  Especially avoid indoor areas where you are likely to be close to others for more than a very short period of time (15 minutes) or whose workers are close to many other people, such as a tattoo parlor, hair or nail salon, restaurant, concert, party or movie theater.  If you must go to a store, try to go to one that makes appointments with customers or limits the number of customers, and spend less than one hour indoors to reduce exposure to any coronavirus that is in the air.

In summary:

  • Stay at home or go outside in your yard or neighborhood where you can keep at least 6 feet away from others
  • Avoid public spaces where there are other people, especially indoors
  • Avoid public transportation when possible and unnecessary travel
  • Avoid all social gatherings that are indoors or where people are close together
  • Work from home if possible
  • Stay at least 6 feet away from people when out in public (indoors or outdoors). Further away is even better, especially if people are singing or talking, or if there isn’t good air filtration.
  • Avoid physical contact in social situations, such as shaking hands, hugging or kissing

AND

  • Wash your hands using soap and water for at least 20 seconds, especially after being out in public
  • Use alcohol-based hand sanitizer when soap and water aren’t available (or wash your hands as soon as you get home)
  • Avoid touching your face when your hands aren’t clean or you are out in public
  • Avoid contact with people you don’t know very well
  • Put the toilet seat down before flushing in a shared or public bathroom
  • A lower priority would be to clean and disinfect surfaces, and only those in your home or workplace that could expose you frequently to the virus, including doorknobs, light switches, faucet handles, and phones. An antibacterial cleaning agent won’t kill a virus, so try to find one that is effective for killing viruses.

If you have a weakened immune system or other serious health problems, here are extra steps to protect yourself:

  • Make a plan with your doctor to monitor for symptoms
  • Avoid friends and family except those you live with or depend on for essentials.  Otherwise, rely on your phone or computer to maintain contact.
  • Have a plan with your loved ones or caregiver if you or they get sick
  • Have the medications you rely on and order any you need in advance (to be delivered, if possible)
  • Ask a friend or family member to shop for groceries for you
  • Wash your hands (20 seconds with soap and water) even more often if you are exposed to others

What should I do if I develop symptoms?

If you develop more than one of the symptoms listed above, call your doctor.  If you have severe symptoms, such as difficulty breathing, persistent chest pain or pressure, confusion or inability to awaken, or blueish color in the lips or face, you need to call 911. Tell the 911 operator that you think you have COVID-19 so the responders can take the necessary precautions to protect themselves.

People who experience mild symptoms can usually stay home and will recover in about 2 weeks. Do not just show up at the doctor’s office with symptoms:  Call them first so you have tell them about your symptoms and any other health problems so that they can help decide what to do.  If you do become sick, you can take the following steps to protect others:

  • Stay home, unless you need essential medical care
  • Wear a facemask when you are near others.  (People caring for you should also wear a facemask).
  • Stay away from others in your home as much as possible
  • Cover your mouth and nose when you cough or sneeze, properly dispose of tissues, and wash your hands
  • Monitor your symptoms and temperature

If you were not tested for COVID-19, you should follow those steps until at least one or two weeks have passed since you first noticed symptoms or your fever or other symptoms go  away for 3 full days without medicine.  If you have been diagnosed with COVID-19 based on test results, you should follow those same steps until you have 2 negative test results taken 24-hours apart, and your symptoms improve.

What if my other scheduled medical treatment is delayed?

When a person is diagnosed with a serious disease, they are likely to want treatment as soon as possible. If you don’t have COVID-19, you don’t want to be exposed to it during surgery, testing, or follow-up appointments. Treatment or testing may seem more urgent than it really is, but it is definitely more important than going to a restaurant, store, or party.  Some medical centers are overwhelmed with Covid-19 patients, and others are not. Talk to your doctor about what is the best strategy to get the treatment you need when it is safe to do so.

Questions?

We are here to help by answering your questions.  We do not provide medical care.  If you have questions contact info@center4research.org and we’ll get back to you as soon as possible.

How to Report Problems With Medical Products to the FDA

National Center for Health Research.


Every year, tens of thousands of consumers suspect that their medicines or medical devices might be causing unexpected side effects. Side effects – also called adverse reactions – can be quite minor, such as a rash or stomach upset, or very serious, such as mental confusion, heart damage or an autoimmune reaction. It is sometimes difficult to tell if the health problem is caused by the medical product or is merely a coincidence. That is why serious problems that are possibly related to a medical product should be reported to your physician and to the Food and Drug Administration (FDA). You do not have to be certain that the health problem is caused by the medical product – the purpose of a tracking program is to figure out if there is a problem by looking for a pattern in the reports. By tracking these reports, the FDA can determine if there is a pattern that may indicate the need to warn consumers or even to withdraw a product from the market.

The FDA has a program called MedWatch for reporting serious reactions and problems with medical products, including drugs and implanted devices.

The process is relatively simple and is outlined on the MedWatch website. You may ask your doctor to fill out a MedWatch form detailing the problem you have been experiencing. The MedWatch form is available online or you or your doctor can request a copy of the form by calling the FDA toll free at 1-888-INFO-FDA (1-888-463-6332).

If for some reason you do not wish to have the form filled out by your doctor or your doctor refuses to fill out the form (doctors are not required by law to complete a report to the FDA), then you can complete the form yourself. MedWatch provides a set of instructions for completing the form on their website, as well as an online form that you can submit on the website.

If you prefer to report your problem over the telephone, you can do that by calling the at 1-800-FDA-1088.

If you have questions or comments about a specific drug or medical device, you can call the FDA toll free information number at 1-888-INFO-FDA (1-888-463-6332), press 2, followed by 1 for information, then:

  • for dietary supplements, press 2
  • for drug products, press 3
  • for medical devices, press 4
  • for biologics, including human cells, tissues and cellular and tissue-based products, press 6

Reporting problems helps fix them and ensure that other patients do not experience the same unexpected side effects or reactions.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

Radiation Therapy for Ductal Carcinoma In Situ (DCIS)

Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund.


In recent years, ductal carcinoma in situ (DCIS) has become one of the most commonly diagnosed breast conditions. It is often referred to as “stage zero breast cancer” or a “pre-cancer.” It is a non-invasive breast condition that is usually diagnosed on a mammogram when it is so small that it has not formed a lump. In DCIS, some of the cells lining the ducts (the parts of the breast that secrete milk) have developed abnormally, but the abnormality has not spread to other breast cells.

DCIS is not painful or dangerous, but it sometimes develops into breast cancer in the future if it is not treated. If it develops into breast cancer, it can spread.  If that happens, it is called invasive breast cancer. The goal of treating invasive cancer is to prevent it from spreading to the lungs, bones, brain, or other parts of the body, where it can be fatal. Since DCIS is not an invasive cancer, it is even less of a threat than Stage 1 or Stage 2 breast cancer, which are the earliest types of invasive cancer.1  For more information, see our free DCIS booklet, and our other articles on DCIS.

Most women with DCIS will never develop invasive cancer whether they are treated or not.  Unfortunately, it is impossible to predict which women with DCIS will develop cancer and which ones won’t. That’s why treatment is recommended. A woman with DCIS does not need all the same treatments as a woman diagnosed with invasive breast cancer, but surgery is almost always recommended. Most DCIS patients will choose a lumpectomy (which removes the DCIS but does not remove the entire breast), and radiation therapy is usually recommended for those women to destroy any stray abnormal cells in the same breast.1

Is Radiation Necessary?

Doctors usually recommend radiation therapy for lumpectomy patients, but since it is inconvenient and has some side effects, many women prefer to avoid it.  In fact, some DCIS patients decide to have a mastectomy because they do not want to undergo radiation.  However, mastectomy is a much more radical surgery and is very rarely a good idea for DCIS patients. That’s because almost all women with DCIS live long lives, and undergoing radiation does not affect whether DCIS patients live a long life or not.

Instead, the main advantage of radiation for DCIS is to prevent recurrence of DCIS in the breast where the DCIS was removed. A study of more than 1,700 women with DCIS who underwent a lumpectomy evaluated different treatment options.4  The women were randomly assigned either to radiation, tamoxifen, radiation plus tamoxifen, or no treatment after surgery.  Undergoing radiation had a very small benefit for women in general, and has little impact on your chances of living a cancer-free life.

In women treated with radiation, about 10% developed DCIS or breast cancer within the next 10 years after surgery, and it made no difference whether these women took tamoxifen or not. And while the vast majority of women were alive 10 years later, their chances of survival were no different whether they were treated with radiation, tamoxifen, both, or neither.4  

For women who did not have radiation therapy, tamoxifen reduced the chances of developing DCIS within 10 years in the same breast by about 3% and the chances of developing DCIS in the other breast by about 1%. Tamoxifen did not significantly decrease the chances of developing invasive breast cancer in the same breast, and only reduced the chances of developing invasive cancer in the opposite breast by about 1%.4

So why do doctors so strongly recommend radiation and hormone therapy for DCIS?  Doctors tend to focus on reducing “relative risk” rather than actual risk. So, if a  treatment decreases the chances of recurrence by about 50% that sounds impressive — but 50% of a 16% chance is 8%, for example, and that isn’t much of a difference. And 50% of a 6% chance of recurrence is even less meaningful.  Most important, it doesn’t affect survival so women can skip radiation now and choose it later if they have a recurrence. In contrast, if a woman has radiation after a lumpectomy and later has a recurrence anyway, she can’t undergo radiation again.

When is radiation most important for DCIS?  It is more likely to benefit younger women (especially women diagnosed before age 40), women with more serious types of DCIS (a high grade DCIS called comedo), and women with a family history of breast cancer.

What is the benefit of hormone therapy for women also undergoing radiation therapy?

Tamoxifen blocks the effects of estrogen on breast cells, which can stop the growth of cancer cells that are sensitive to estrogen. A study of more than 1,800 pre-menopausal and post-menopausal women with DCIS evaluated the benefits of tamoxifen for women who had lumpectomy and radiation treatment. These women were randomly assigned to take tamoxifen for 5 years or a placebo (sugar pill). The study found that after 5 years, women who took tamoxifen were about 5% less likely to develop either DCIS or cancer in the same breast, cancer in the opposite breast, or distant cancer spread.  The difference was 8 of women taking tamoxifen compared to 13% of women taking placebo. However, the vast majority of women survived and they did not live any longer whether they took tamoxifen or not.1

For postmenopausal women, aromatase inhibitors may be used instead of tamoxifen. Aromatase inhibitors block the body’s ability to make estrogen. A study of more than 3,000 post-menopausal women with DCIS evaluated the benefits of hormone treatment for women who had lumpectomy and radiation treatment. These women were randomly assigned to take tamoxifen or anastrozole for 5 years. The study found that after 5 years, compared to women taking tamoxifen, the women taking anastrozole were 2% less likely to develop either DCIS or cancer in the same breast, cancer in the opposite breast, or distant cancer spread.  The difference was about 8% of women taking tamoxifen compared to 6% taking anastrozole.  As in the previous study, the vast majority of women survived and those taking anastrozole did not live any longer than women taking tamoxifen.2

That was a very small benefit for anastrozole compared to tamoxifen, and another study of post-menopausal women with DCIS found no difference between the two hormone treatments.3

Bottom Line:  Radiation and hormone therapy both have benefits for most women who undergo lumpectomy, because they decrease the chances of DCIS returning after surgery.  However, the benefits are quite modest and neither of these treatments affect how long women live, because almost all women diagnosed with DCIS are still alive 20 years later.

References:

  1. National Cancer Institute. Breast Cancer Treatment PDQ. (Feb. 2018). Available online: https://www.cancer.gov/types/breast/hp/breast-treatment-pdq#link/_1576_toc
  2. Margolese, Richard G et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial.The Lancet. 2016;387(10021): 849 – 856.
  3. Forbes, John F et al. Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. The Lancet.2016;387(10021): 866 – 873.
  4. Cuzick, Jack et al. Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial. The Lancet Oncology. 2011; 12(1): 21 – 29

Which Breast Implants are Safest for Mastectomy Patients?

Diana Zuckerman, PhD, Madris Tomes, and Amelia Murphy, National Center for Health Research and Device Events

Based on the summary of book chapter in Breast Implants, Rene Simon (ed.), Nova Science Publishers, 2017.

Our new book chapter on breast implants explains that the 55-year history of breast implants reflects repeated efforts to improve their safety and effectiveness by reducing the cosmetic problems and health complications that develop during the years while they are in the human body. The most recent effort is the type of highly cohesive breast implants known as “gummy bear implants” because of the thick gel that is described as similar to gummy bear candies. The goal of the more cohesive gel is to make implants last longer and be less likely to leak. First approved in the United States in 2012, adverse event reports indicate that this newest generation of implants causes complications similar to older generations of silicone gel breast implants.

The first breast implants, made in the 1960’s, were for cosmetic enhancement. When women’s augmented breasts became hard over time, implant manufacturers responded by making the silicone gel thinner. One manufacturer, Surgitek, added polyurethane foam to the outside to make the breasts feel softer. Those design changes caused other problems, however: the thinner gel had a tendency to “bleed” through the silicone elastomer shell, which contributed to the most common complication, capsular contracture. Breast implants made with thinner gel also ruptured and leaked more easily, and the gel broke down into silicone oil which could migrate to other organs or cause silicone granulomas inside their bodies. The polyurethane foam caused other problems: implant removal was very difficult and women lost their breast tissue during explant surgery, and the foam was found to break down to a known carcinogen.

The Food and Drug Administration (FDA) did not require breast implant manufacturers to submit data to prove the implants were safe and effective until 1992. By that time, the manufacturers had developed implants with a thicker shell and a more cohesive silicone gel. However, the studies revealed that, like the earlier implants, the more cohesive implants did not “last a lifetime” as had been claimed. As a result, manufacturers continued to modify the silicone gel to make it less likely to rupture and leak.

Despite claims that gummy bear implants are safer than other breast implants, a 5-year study found that the rupture rate was more than 4% for first-time augmentation patients.  The percentage of women needing additional surgery within 5 years ranged from 17% to 48%, depending on whether the patients were augmentation patients or reconstruction patients, and whether the gummy bear implants replaced previous implants. Our analysis found that from January 1, 2008 through June 30, 2017, 1298 adverse event reports for silicone gel breast implants were made to the FDA, 252 (19%) of which were for gummy bear implants. This is very high when you keep in mind that gummy bear implants were relatively rare in the U.S. prior to FDA approval in 2012. This chapter puts these statistics in the context of what is known about the safety of silicone breast implants and how that has changed over time.

Copies of the entire book chapter are available upon request at info@center4research.org

Could a Common and Inexpensive Heart Medicine (Beta-Blockers) Help Cancer Patients Live Longer?

Jessica Cote, Cancer Prevention & Treatment Fund

Beta-blockers are drugs that are usually prescribed for high blood pressure (hypertension), irregularities in heart beat (arrhythmias), and to prevent heart attacks after a first heart attack has already occurred. Beta-blockers work by stopping adrenaline and noradrenaline from triggering the body’s “fight or flight” response to stress or danger.  Beta blockers help the body feel more relaxed, lowering blood pressure and increasing blood flow.

Beta-blockers are taken by so many Americans that they are the fifth most widely prescribed class of drugs.[1]  Since they are safe and inexpensive, wouldn’t it be great if they were effective for treating cancer, too?

Doctors and researchers noticed that when cancer patients took beta-blockers because of their heart disease, they tended to live longer than other cancer patients. They decided to study whether beta-blockers significantly improve survival for several different types of cancer.

How Beta-Blockers Affect Different Types of Cancer

Non-Small Cell Lung Cancer

In a study published in Annals of Oncology in 2013, Hong-Mei Wang and colleagues at the MD Anderson Center in Texas reviewed data from 722 patients with non-small cell lung cancer, the most common type of lung cancer.[2] All patients received radiation therapy to treat their lung cancer, but only some took beta-blockers for heart conditions. Almost all the patients in the study had stage III cancer.

The 155 patients taking beta-blockers survived for an average of almost 24 months while the 567 patients not taking beta-blockers survived for an average of about 18.5 months. In addition to living longer, patients taking beta-blockers lived longer without their lung cancer returning (disease-free survival) and without it spreading to other parts of their body (distant metastasis-free survival). The researchers statistically controlled for other factors that could affect survival, such as the patient’s age, the stage of the cancer, the use of aspirin, and use of chemotherapy, to be sure that the beta-blockers were truly helping slow down the cancer.

Breast Cancer

Six studies published since 2010 have examined how beta-blockers affected breast cancer patients who had been treated with beta blockers for heart disease at the same time they were treated for cancer.[3] All six studies found that breast cancer patients lived longer if they were taking beta-blockers.

A new clinical trial is currently underway to find out what happens to women who take beta-blockers specifically as a breast cancer treatment. However, the results are not yet available.

Ovarian Cancer

Elena Diaz and colleagues at Cedars-Sinai Medical Center published a study in 2012 of 248 women who were treated with surgery and chemotherapy for their ovarian cancer.[4] Twenty-three patients took beta-blockers for high blood pressure or other heart conditions during their cancer treatment. The results showed that women who took beta-blockers were more likely to remain free of ovarian cancer after treatment than women who didn’t take beta-blockers (progression-free survival) and less likely to die from ovarian cancer (disease-specific survival). Women taking beta-blocker lived an average of 56 months after cancer treatment while those not taking beta blocker lived an average of 48 months after treatment. In addition, women who took beta-blockers were 54% less likely to die during the more than 12 years that researchers tracked their health, compared to the women who did not take beta blockers.

Pancreatic Cancer

Hussein Al-Wadei and colleagues at the University of Tennessee published a study in 2009 that showed how beta-blockers were able to halt the progression of pancreatic cancer in animals.[5]  Research is needed to determine if beta-blockers is effective for pancreatic cancer in humans.

Why Might Beta-Blockers Help Cancer Patients?

Adrenaline and noradrenaline, the two neurotransmitters that stimulate the “fight or flight” response, probably trigger tumor growth. When beta-blockers halt the activity of these neurotransmitters, they may therefore help reduce the growth of cancerous tumors.

When the FDA makes a decision to approve a drug, it is always for specific symptoms or diseases, and the risks and benefits for that specific treatment is what the FDA considers. Although generally safe, beta-blockers can cause fatigue, headache, upset stomach, constipation, diarrhea, dizziness, cold hands, shortness of breath, and trouble sleeping.   For that reason, it is not a good idea to use beta-blockers to treat cancer unless there is clear evidence that they are likely to work — that the benefits outweigh those risks.  And, that is the reason that the breast cancer study that is now underway only includes beta blockers for 2 days before and 3 days after the cancer surgery.

In addition to being approved by the FDA to control blood pressure and heart disease, beta-blockers are also approved for preventing migraines, treating essential tremor (ET) in the head, arms and legs, and, as eye drops to treat glaucoma.  Doctors prescribe beta blockers for other reasons , but  taking medicines for non-approved uses can be risky. If a use is not approved, it often means that there is no conclusive evidence showing that the benefits outweigh the risks.  However, it sometimes means that the companies making the drug don’t think FDA approval for the new use will benefit the company financially.  The latter is especially true for drugs that are already on the market and inexpensive, such as beta-blockers.

The Bottom Line

  • Beta-blockers are usually used to treat heart conditions like high blood pressure and an irregular heart beat. New research has shown that these inexpensive drugs may help cancer patients live longer.
  • More research is needed to know which beta-blockers work best when added to cancer surgery, radiation, or chemotherapy, and for which cancers.
  • If you already take beta-blockers for a heart condition, they may provide keep taking them if you are also diagnosed with cancer. If you don’t take beta-blockers but are diagnosed with non-small cell lung cancer or early breast cancer, you may want to ask your doctor whether to take beta-blockers for two days before and three days after your cancer surgery.

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

References

  1. Consumer Reports, Best Buy Drugs: “Using Beta-blockers to treat: High Blood Pressure and Heart Disease.” Updated March 2011. https://www.consumerreports.org/health/resources/pdf/best-buy-drugs/CU-Betablockers-FIN060109.pdf
  2. Wang HM, Liao ZX, Komaki R et al. Improved survival outcomes with the incidental use of beta-blockers among patients with non-small-cell lung cancer treated with definitive radiation therapy. Annals of Oncology 2013.
  3. Barron TI, Sharp L, Visvanathan K. Beta-adrenergic blocking drugs in breast cancer: a perspective review. Therapeutic Advances in Medical Oncology 2012; 4(3):113-125.
  4. Diaz ES, Karlan BY, Andrew JL. Impact of beta blockers on epithelial ovarian cancer survival. Gynecologic Oncology 2012; 127(2):375-378.
  5. Al-Wadei HAN, Al-Wadei  MH, Schuller HM. Prevention of pancreatic cancer by the beta-blocker propranolol. Anticancer Drugs 2009; 20(6):477-482.

The Benefits of Exercise After Getting Diagnosed with Cancer

Morgan Wharton, Cancer Prevention and Treatment Fund

You may have heard that regular exercise can reduce your risk of developing cancer, but did you know it’s also good for cancer patients who are undergoing or have completed treatment?

Is Exercise Good for Everyone Diagnosed with Cancer?

Exercise has proven benefits for cancer patients, ranging from improved fitness and higher quality of life to reduced rates of recurrence and a longer life.1-9 What we know about exercise and cancer mostly comes from studying patients with breast or colon cancer, but there’s reason to believe that there are benefits of exercise for men and women suffering from all types of cancer, even cancer as advanced as Stage III.3, 7

The best news of all: It doesn’t matter if you were fit before you got diagnosed. Whether or not you exercised before has no bearing on what exercise can do for you during and after treatment.3, 4, 6 So, it’s never too late to use exercise to fight cancer. If you’re coping with cancer or its aftermath, now is the time.

What Does the Science Show about Exercise for Cancer Patients?

Many studies have shown that exercise is beneficial to cancer patients, but no one is sure exactly why. Earlier studies suggested that exercise may help women avoid breast cancer or a recurrence of it by decreasing female hormones that feed cancer in the breast,10-11 or by lowering inflammation in the body,12 a suspected contributor to many diseases. In 2014, a study was published that provides a new possible explanation for how exercise helps the body fight cancer.13 Researchers looked at irisin, a protein released from muscles after exercise, to see how it would affect breast cancer cells and healthy breast cells in test tubes. What they found was that when breast cancer cells came into contact with irisin, they started to self-destruct in a programmed way. While the exercise protein reduced the number of malignant cells and their ability to move around, it left the healthy cells unharmed! The researchers also found that irisin made Doxorubicin, a chemotherapy drug commonly given to breast cancer patients, more effective at killing cancer cells. Though this study did not look at what happens to cancer cells in actual patients after they exercise, it could help explain why other studies have found that cancer patients who are physically active feel better during treatment and are less likely to have their cancer come back.

A study from 2020 found that exercise is beneficial for preventing cancer deaths. It examined how active people were per day, and found that people who were more active were less likely to die from cancer by a follow-up 6 years later.14 However, the study did not include people who were undergoing cancer treatment when the study was measuring physical activity, which makes sense since cancer treatment can drastically reduce the ability to exercise. This means that the results of the study are not specifically about people undergoing cancer treatment.

Studies that did look at patients focused on those beginning exercise (such as walking or aerobic exercise with weight training) somewhere between 2 weeks and 1 year after completing cancer treatment. In these studies, treatment could include surgery, chemotherapy, radiation, or a combination of these therapies.1, 2, 3, 4, 6, 7, 8 Some studies also examined the effects of exercise during cancer treatment.5, 9

Less Body Fat and Better Immune System:

Studies have shown that in cancer patients, exercise during or after treatment reduces fat and improves body mass index (BMI).2, 6, 9 Exercise lowers blood pressure, boosts the immune system, and increases bone mineral density.6, 8, 9 Denser bones means fewer fractures.

Improved Fitness:

As expected, cancer patients who exercise regularly during and after treatment reported increases in strength, walking ability, aerobic capacity, and flexibility.2, 6, 9

Less Fatigue and Fewer Side Effects from Treatment:

Cancer patients who had completed treatment reported fewer negative side effects from treatment once they began to exercise regularly.7 Patients who exercised during treatment reported less nausea and less difficulty sleeping.9 The most commonly reported improvement was reduced fatigue. 6, 8, 9

Better Quality of Life:

In addition to the physical health benefits of exercise, cancer patients who exercised also reported improved mental and emotional well-being.2 Patients who exercised during treatment and those who began to exercise afterwards frequently reported an increase in quality of life.9 Patients who began to exercise regularly after treatment experienced less anxiety and a renewed “fighting spirit.”9 Cancer patients over the age of 80 who exercised regularly during their weeks or months of treatment reported less loss of memory.5

Reduced Risk of the Cancer Coming Back:

Because exercise improves the immune system, cancer patients who exercise regularly lower their risk of the cancer returning.1, 2, 3, 8Patients who exercise are less likely to die from cancer and are more likely to live longer than patients who don’t exercise.14

What Kind of Exercise Should I Do?

Aerobic activity of light to moderate intensity was the most common type of exercise in the studies of cancer patients.2, 3, 6, 8, 9 Combining aerobic exercise with walking and resistance training (such as weight lifting or using resistance bands) led to greater health benefits than aerobic activity alone.2, 6, 8 

Most studies used Metabolic Equivalent (MET) hours to measure physical activity by level of intensity. MET hours measure the energy output of various activities compared to the energy used by the body when at rest. Activities that require more effort have a higher MET score than activities with lower intensities. One study suggested that 18-27 MET hours per week represents the ideal rate of exercise, because that group showed the lowest rate of recurrence and more activity did not lead to increased benefits.7 Having a MET score comparable to 6 or more hours of walking in a week showed a 47% higher chance of survival without recurrence.3 Click here for a chart of various activities and their MET hour equivalent, so you can calculate your weekly exercise in MET hours and maximize your benefits from exercise.

Walking can improve the health of cancer patients. Studies estimate that the greatest benefit from walking is seen in patients who walk at an average speed(a 20 minute mile) for 3-5 hours weekly.7 Patients who walked just 1 hour per week, regardless of walking speed, showed improvements over the group of patients who reported no physical activity in a week.7

To get the most out exercise, you need to make it a habit—something you commit to for the long-term. That’s why it is better to start small, with easily achievable changes like using the stairs regularly instead of the elevator or walking each evening after dinner. Remember not to set unrealistic goals, because it is better to start small and keep it up than to try to do too much and give up. Don’t miss the chance to get at least some benefit from this easy, free strategy to fight cancer.

The bottom line

Exercise helps individuals who are undergoing cancer treatment and those who have completed cancer treatment. Cancer patients who exercise regularly during and after treatment can expect fewer side-effects from treatment, less fatigue, and better overall fitness and health. Patients who exercise are less likely to experience a return of cancer in the future and are more likely to live longer, healthier lives.

You should try to walk at least six hours a week at an average pace (about 1 mile per 20 minutes).

Even minimum exercise, like walking one hour per week, can improve the health of cancer patients who have completed treatment, compared to cancer patients who do not exercise at all.The benefits from exercise can be seen in all cancer patients, regardless of whether or not they exercised regularly before they were diagnosed with cancer. It’s never too late to begin to exercise and improve your health!

References

  1. Barbara Sternfeld, E.W., Charles P. Quesenberry, Jr., Adrienne L. Castillo, Marilyn Kwan, Martha L. Slattery, and Bette J. Caan, Physical activity and risk of recurrence and mortality in breast cancer survivors: Findings from the LACE study. Cancer Epidemiology, Biomarkers & Prevention, 2009. 18(1): p. 87-95.
  2. Daniel Y T Fong, J.W.C.H., Bryant P H Hui, Antoinette M Lee, Duncan J Macfarlane, Sharron S K Leung, Ester Cerin, Wynnie Y Y Chan, Ivy P F Leung, Sharon H S Lam, Aliki J Taylor, Kar-keung Cheng, Physical activity for cancer survivors: Meta analysis of randomised controlled trials. British Medical Journal, 2012. 344(70).
  3. Jeffrey A. Meyerhardt, D.H., Donna Niedzwiecki, Donna Hollis, Leonard B. Satz, Robert J. Mayer, James Thomas, Heidi Nelson, Renaud Whittom, Alexander Hantel, Richard L. Schilsky, and Charles S. Fuchs, Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: Findings from CALGB 89803. Journal of Clinical Oncology, 2006. 24(22): p. 3635-3541.
  4. Jeffrey A. Meyerhardt, E.L.G., Michelle D. Holmes, Andrew T. Chan, Jennifer A. Chan, Graham A. Colditz, and Charles S. Fuchs, Physical activity and survival after colorectal cancer diagnosis. Journal of Clinical Oncology, 2006. 24(22): p. 3527-3534.
  5. LK Sprod, S.M., W Demark-Wahnefried, MC Janelsins, LJ Peppone, GR Morrow, R Lord, H Gross, KM Mustian, Exercise and cancer treatment symptoms in 408 newly diagnosed older cancer patients. Journal of Geriatric Oncology, 2012. 3(2): p. 90-97.
  6. Margaret L. McNeely, K.L.C., Brian H. Rowe, Terry P. Klassen, John R. Mackey, Kerry S. Courneya, Effects of exercise on breast cancer patients and survivors: A systematic review and meta analysis. Canadian Medical Association Journal, 2006. 175(1): p. 34-41.
  7. Michelle D. Holmes, W.Y.C., Diane Fesknich, Candyce H. Kroenke, Graham A. Colditz, Physical activity and survival after breast cancer diagnosis. Journal of the American Medical Association, 2005. 293(20): p. 2479-2486.
  8. Rosalind R. Spence, K.C.H., Wendy J. Brown, Exercise and cancer rehabilitation: A systematic review. Cancer Treatment Reviews, 2009. 36: p. 185-194.
  9. Ruud Knols, N.K.A., Daniel Uebelhart, Jaap Fransen, and Geert Aufdemkampe, Physical exercise in cancer patients during and after medical treatment: A systematic review of randomized and controlled clinical trials. Journal of Clinical Oncology, 2005. 23(16): p. 3830-3842.
  10. Key T, Appleby P, Barnes I, Reeves G. Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst. Apr 17 2002;94(8):606-616.
  11. McTiernan A, Tworoger SS, Ulrich CM, et al. Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trial. Cancer Res. Apr 15 2004;64(8):2923-2928.
  12. Friedenreich CM, Neilson HK, Woolcott CG, et al. Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women. Cancer Prevention Research. January 1, 2012 2012;5(1):98-108.
  13. Gannon NP, Vaughan RA, Garcia-Smith R, Bisoffi M, Trujillo KA. Effects of the exercise-inducible myokine irisin on malignant and non-malignant breast epithelial cell behavior in vitro. Int J Cancer. Feb 15 2015;136(4):E197-202.
  14.  Gilchrist SC, Howard VJ, Akinyemiju T, Judd SE, Cushman M, Hooker SP, Diaz KM. Association of Sedentary Behavior With Cancer Mortality in Middle-aged and Older US Adults. JAMA Oncology. 2020;6(8):1210–1217.

Do cancer researchers make new treatments sound better than they really are?

By Diana Zuckerman, Ph.D. and Jennifer Focht
Updated 2015

Everyone wants to find a cure for cancer, but some medical researchers are exaggerating the effectiveness of the treatments they study. In some cases, information about side effects and other risks are downplayed as well.

To find out if a treatment works, medical researchers compare patients who take the treatment to patients who take a different treatment, or take no treatment at all. The outcome that matters to patients is whether the treatment will cure them or at least help them live longer, with a better quality of life.

That isn’t always the outcome that scientists study, however. For example, a company may instead want to measure whether the treatment successfully got rid of cancer cells or slowed down the progression of cancer. These kinds of measures are called “surrogate endpoints” or “biomarkers” because they substitute for the outcome that really matters (health and survival) by evaluating things that can be studied more quickly and easily and are expected to be related to health and survival – but might not be. Unfortunately, in their desire to get more cancer treatments to market more quickly, many cancer drugs are approved by the FDA based on these preliminary kinds of findings, rather than based on improved health or survival. It may take years or even decades to find out if the new drugs really save lives or improve the quality of patients’ lives. Research published in 2015 indicates that the studies done after recent cancer drugs were approved were more likely to show they don’t save lives or improve health than to show that they do.1

For these and other reasons, published studies of cancer treatment can be misleading.

In addition to FDA lowering the standards for cancer drugs, there are other reasons why doctors and patients may not have all the information they need to help patients make the best treatment decisions. For example, medical journals prefer to publish articles about treatments that are effective, instead of treatments that are not. New, effective treatments are more exciting, but for patients, knowing which drugs don’t work well is just as important as knowing which ones are effective. If researchers learn that a treatment doesn’t actually work, they may have a very hard time getting the results published. And, if the research was funded by the company that makes the treatment, as it usually is, that company will probably not want the study to be published.

Even when researchers sincerely want to publish their study results to help patients, they may find that being completely honest about unimpressive or ambiguous results means they won’t get the study published. Publications are important to scientists, so what can they do to improve their chances of getting the study published in a major medical journal? Those researchers might find it easier to get the article published if they focus on the positive results (such as slowing down the spread of cancer) and ignore the negative results (for example, if the patients did not live longer because the toxic effects of the treatment caused them to die anyway).

Dr. Francisco Emilio Vera-Badillo and his colleagues at the University of Toronto reviewed published articles on breast cancer treatments and found that one out of three misrepresented a treatment’s overall ineffectiveness by highlighting some other benefit. For example, a study might show that patients’ quality of life improved slightly when they started the treatment in question. Feeling better is important, even if only for a short time – but it is a subjective measure that could be influenced by feeling hopeful about getting a new medication. If the purpose of the study was to determine whether or not the treatment helped patients live longer, or at least had a major health benefit from the treatment, then this secondary benefit that a few of the patients felt a little better is just that: secondary. Can a treatment be considered “effective” if it doesn’t do what it is supposed to do?  Is it worth the potential risks to one’s health (most cancer drugs are highly toxic) and the costs (which may be tens of thousands of dollars) to take a drug that isn’t really effective? If the benefits of the new drug are very modest, there may be other, less dangerous and less expensive strategies that could help patients much more. And, even more important, in the same analysis, two out of three of the published articles described the results of their research in a way that glossed over negative side effects, especially when the treatment was effective.2 But negative side effects can be very harmful, or even deadly, so it is important that they be accurate reported.

A separate review of published articles on a variety of health treatments—not just cancer treatments—showed that 16% reported no data about side effects. In nearly one-third of the articles, information on side effects was reported inadequately.3 For example, when researchers found an increased risk of heart attack associated with the arthritis drug Vioxx, they changed the reported time frame of their study when they wrote up their results.4 As a result, the published article did not mention the participants who had experienced heart attacks during the last month of the trial and Vioxx seemed safer than it actually was. (When these risks became known, Vioxx was recalled in 2004.)

Bottom line:

Information about a drug’s effectiveness and side effects are both important, and both should be reported in studies so that patients and their doctors have a full understanding of treatment options. In many areas of medicine, research tends to over-emphasize effectiveness and down-play side effects, and for cancer drugs this tendency may be even more pronounced. Many cancer researchers are calling for stricter guidelines, like standardizing reporting of results to make it more obvious when information is missing, but that will only address part of the problem.

In the meantime, what can you do to ensure the safety of the treatment you are receiving? If you have just been diagnosed with cancer, you may want to consider an older treatment over a newer one. Why? Because newer drugs are often approved on preliminary evidence and wishful thinking, and too often years pass before the true risks and benefits are known. In most cases, newer treatments haven’t been researched as thoroughly as older ones that have been sold for many years. If your doctor wants you to switch to a newer treatment, ask him or her to review each of the side effects with you and compare them to the side effects of your old treatment. If after starting a new treatment, you notice side effects—expected or unexpected—let your doctor know right away. Ask as many questions about your treatment as you want. There are no stupid questions—only stupid answers. You have the right to complete information on your treatment’s effectiveness and risks.

For information on the influence of industry funding on medical research, click here.

Chemotherapy: What is it, and How is it Used?

Austin Van Grack, Cancer Prevention and Treatment Fund

Types of chemotherapy:

Curative chemotherapy
Adjuvant chemotherapy
Neo-adjuvant chemotherapy
Palliative chemotherapy
Maintenance chemotherapy

Patient concerns about chemotherapy:

Patient misunderstandings about chemotherapy
Why are patients confused about chemotherapy?
Health literacy and informed decision making about cancer treatments

Chemotherapy is one of the most common cancer treatments used today. However, 1 in 4 patients receiving chemotherapy do not understand why they’re getting it and how it’s supposed to help them.[1]

Chemotherapy is a cancer treatment that uses one or more drugs to kill cancer cells. It stops or slows the growth of cancer cells, which otherwise may grow quickly.[2]

Types of Chemotherapy

Sometimes the aim of chemotherapy is to get rid of or cure the cancer, but other times the goal is to help somebody with incurable cancer live longer or get relief from some of their cancer symptoms. While there are many different drugs used in chemotherapy (alone or in combinations), there are only five types or uses for chemotherapy. You may hear your doctor use one or more of these terms when talking about your chemotherapy:

  • Curative chemotherapy
  • Adjuvant chemotherapy
  • Neo-adjuvant chemotherapy
  • Palliative chemotherapy
  • Maintenance chemotherapy

Curative Chemotherapy

Curative chemotherapy aims to “cure the cancer,” meaning it is intended to eliminate all cancerous cells, resulting in what doctors call “complete remission.” The majority of patients receiving chemotherapy with the goal of cure are receiving chemotherapy as well as surgery or radiation.

Adjuvant Chemotherapy

Adjuvant chemotherapy is given in addition to other treatments, with the goal of curing cancer or lowering the risk of cancer coming back. Adjuvant therapy is given after surgery or radiation. If given after surgery, it may be called postoperative chemotherapy. Patients usually receive adjuvant chemotherapy when they have a type of cancer that is likely to reoccur, such as breast or colon cancer. Adjuvant therapy may or may not rid the body of all cancer cells but it should at least lower the risk of cancer coming back, or prolong the patient’s life.

Neo-adjuvant Chemotherapy

Neo-adjuvant chemotherapy (sometimes called preoperative chemotherapy), is also given in addition to other treatments, but it is usually given before surgery in order to shrink the tumor and make it easier to remove or treat with radiation. Sometimes “inoperable tumors” can be surgically removed after neo-adjuvant chemotherapy.

For breast cancer patients, neo-adjuvant chemotherapy can sometimes reduce the tumor enough that a woman can choose to have breast-conserving surgery (lumpectomy) instead of having her whole breast removed (mastectomy).[3] Most often neo-adjuvant chemotherapy will be used on breast cancer patients with tumors greater than 2 cm in size and where the cancer has not spread to other parts of the body.

It is important to remember that the goal of neo-adjuvant chemotherapy is not to cure the cancer but to give the patients more options for treatment, including treatments that are more effective and less radical.

Palliative Chemotherapy

Non-curative chemotherapy for prolonging life and reducing symptoms is called palliative chemotherapy. Palliative chemotherapy is often given to patients with advanced cancer in hopes of making patients more comfortable toward the end of life.  It is sometimes given in combination with other cancer treatments.

The type of palliative chemotherapy a patient receives depends on the patient’s type of cancer and prognosis. Palliative chemotherapy is usually for patients with non-small-cell lung cancer, pancreatic cancer, or colon cancer.

Maintenance Chemotherapy

Maintenance chemotherapy is given to help keep the cancer from coming back in patients whose cancer went away after the initial treatment. In other words, the goal of maintenance therapy is to prevent reoccurrence after the cancer has gone into remission.  This kind of chemotherapy, which may include drugs, vaccines or anything shown to kill cancer cells—may be taken for a longer time than other forms of chemotherapy.[4]

Maintenance therapy is most commonly used by patients who are diagnosed with late stage non-small cell lung cancer. Their cancer usually cannot be completely wiped out but it can be reduced and then kept in check for months or even years. Like palliative therapy, maintenance therapy is aimed at prolonging life and keeping the patient from getting worse, not curing the patient.

Maintenance therapy is also called consolidation therapy, post-remission therapy, intensification therapy, or early second-line therapy.[5] Because chemotherapy has terrible side effects and since maintenance therapy is given over long periods of time, it should only be used if it does more good than harm. The maintenance therapy should help the patient feel better or live longer without prolonging suffering.

Patient Concerns About Chemotherapy

Patient Misunderstandings About Chemotherapy

A study in the journal Cancer by Dr. Inga Lennes and her colleagues at Massachusetts General Hospital surveyed 125 newly diagnosed cancer patients who were receiving their first round of chemotherapy. The researchers wanted to see if the patients’ perception of chemotherapy and why they were receiving it matched their doctors’ reasons for giving it. Patients were asked, in writing, to choose from four possible responses describing the goal of their treatment as explained to them by their oncologist:

1) to decrease the chance the disease will return, also called adjuvant treatment;

2) to provide a prolonged time without any evidence of disease, also called cure;

3) to control the growth of the cancer without getting rid of it completely to prolong life; and

4) to reduce side effects and symptoms of the cancer to promote your comfort, also called palliation.

Patients were allowed to choose more than one answer. Patients who selected one or both of the first two responses were categorized as viewing their chemotherapy as curative. Those that selected the third or fourth response viewed their chemotherapy as non-curative.

Three out of four patients correctly identified their oncologist’s reason for prescribing chemotherapy. Nearly all of these patients (99%), however, were the ones being given chemotherapy to cure their cancer and keep it from coming back. Among the 25% of patients who did not correctly identify their oncologist’s reason for prescribing chemotherapy, two-thirds (66%) thought the chemotherapy would cure their cancer when, in fact, that was not the oncologist’s goal. Patients who were undergoing non-curative chemotherapy—to prolong life with cancer and reduce symptoms from cancer – had a harder time understanding what their oncologist hoped to achieve than did patients whose chemotherapy was curative.

Why are Patients Confused About Chemotherapy?

There are many possible reasons why patients misunderstand the goal of their chemotherapy.  Studies show that doctors are not good at communicating bad news and want to appear hopeful.  They may provide written information that some patients can’t understand.

Physician and Patient Optimism

When the prognosis is bad (the patient is not going to survive the cancer), physicians may be deliberately unclear or vague, or they may be overly optimistic about the patient’s chances. As a result, patients have a difficult time accepting that their disease is incurable.

Studies have found that cancer patients want their doctors to “maintain an attitude of hope”, but doing so may mislead or confuse patients with advanced cancer. A small study of 28 patients in three hospitals in England taped the first consultation after the patient had received his or her diagnosis, usually after surgery to remove the cancer had been performed.[6] They found that when doctors are discussing bad or uncertain news about a patient’s prognosis or treatment, they pair it with some positive information.  For example, in one conversation between a patient with laryngeal cancer and his doctor, the doctor gave the bad news that his cancer probably would not be cured, quickly followed by hopeful news and the statement that there is a “very good chance” that radiation “will work.”  This good news-bad news approach can confuse patients and result in unrealistic expectations of treatment.

A study in Australia, using recorded conversations between 118 patients and 9 oncologists, found that 3 out of 4 patients had been told that their cancer was incurable, and 85% had been informed of the aim of treatment.[7] After giving the information, only 10% of physicians checked to see if the patient actually understood it. One way to check if the patient has understood is to have her explain to the doctor what she just heard in her own words.

A different study found that patients who incorrectly believed that their chemotherapy would cure their cancer were the ones who gave their doctors the highest communication scores.[8] Clearly, doctors who put a positive spin on a patient’s condition may be the most popular, but their mixed messages are confusing to patients.

Patients with incurable cancer need optimism to help them cope  with the news that they are going to die.[9] While maintaining hope in the face of death is important, patients with too sunny an outlook can have  unrealistic expectations of treatment.

Health Literacy and Informed Decision Making About Cancer Treatments

Health literacy is the ability of patients to understand health information presented to them that they need to make appropriate health decisions. All patients face the challenge of making treatment decisions based on the information their physicians have provided them. This is especially true for cancer patients, who are faced with new medical terminology, unclear statistics, and often-vague prognoses. Experts agree that the lack of health literacy among cancer patients may make it difficult for them to understand their treatments and their prognosis.

Patients over the age of 60 have some of the lowest levels of health literacy, with as many as 80% struggling to understand paperwork given to them by their doctors, including consent forms.[10] In the U.S., younger patients and patients who are native English speakers understand the purpose of their chemotherapy better than older patients or non-native English speakers.

Patients with low health literacy are less likely to ask questions when they don’t understand what they’re reading or what they’re doctor has told them. This is a chicken and egg situation: people with low health literacy lack the confidence or educational and cultural training to ask questions of people with authority (doctors). Meanwhile, the failure to ask questions and get doubts resolved contributes to low health literacy.

Over the last decade, there has been a shift in the medical community from the concept of informed consent, in which patients agree to the doctor’s recommended course of treatment, to the idea of informed decision-making, in which patents and doctors exchange information, ask each other questions, and come to a final treatment decision together as a team. This more patient-centered approach can help cancer patients understand the goal of their care.

In addition, research shows that cancer patients who asked their doctors at least three questions had a better understanding of their treatment options and were more confident in making decisions.

The Bottom Line

  • 1 out of 4 patients receiving chemotherapy do not understand the goal of therapy.
  • The lack of patient understanding is due to a number of factors, including poor and overly optimistic communication between doctors and cancer patients, low health literacy among patients, and the many new terms used in explaining chemotherapy.
  • Patients who misunderstand the goal of their chemotherapy may opt for longer or more aggressive treatment than they would if they understood their prognosis better.
  • To improve communication between cancer patients and their doctors, doctors should use the communication technique known as “ask, tell, ask.” Doctors first ask what the patient wants to know, then they provide the information the patient has asked for, and then they ask the patient to explain what they’ve just learned.8
  • Doctors should regularly ask their patients to summarize what they have just heard, including the goal of the chemotherapy.  Patients should ask doctors questions, including asking what terms mean as well as anything they are uncertain or worried about.

References:

    1. Lennes IT, Temel JS, Hoedt H et al. Predictors of Newly Diagnosed Cancer Patients’ Understanding of the Goals of Their Care at Initiation of Chemotherapy. Cancer. 2012; DOI: 10.1002/cncr.27787
    2. National Cancer Institute. Chemotherapy and You: Support for People With Cancer. Accessed November 28, 2012. http://www.cancer.gov/cancertopics/coping/chemotherapy-and-you/page2.
    3. Thompson AM, Moulder-Thompson SL. Neoadjuvant treatment of breast cancer. Annals of Oncology. 2012;23:231-36. Doi:10.1093/annonc/mds324.
    4. National Cancer Institute.  NCI Dictionary of Cancer Terms. Accessed November 9, 2012. http://www.cancer.gov/dictionary?CdrID=45768
    5. Owonikoko TK, Ramalingam SS, Belani CP. Maintenance Therapy for Advanced Non-small Cell Lung Cancer: Current Status, Controversies, and Emerging Consensus. Clinical Cancer Research. 2010;16:2496-2504. Doi:10.1158/1078-0432.CCR-09-2328.
    6. Leydon GM. “Yours is potentially serious but most of these are cured”: optimistic communication in UJ outpatient oncology consultations. Psycho-Oncology. 2008; 17: 1081-88. DOI: 10.1002/pon.1392.
    7. Gattellari M, Vaigt KJ, Butnow, PN et al. When the Treatment Goal Is Not Cure: Are Cancer Patients Equipped to Make Informed Decisions? Journal of Clinical Oncology. 2002; 20; 2:503-13.
    8. Weeks JC, Catalano PJ, Cronin A et al. Patients’ Expectations about Effects of Chemotherapy for Advanced Cancer. NEJM. 2012; 367:1616-1625. DOI: 10.1056/NEJMoa1204410
    9. Smith TJ, Longo DL. Talking with Patients about Dying. NEJM. 2012; 367:1651-1652. DOI: 10.1056/NEJMe1211160.
    10. Amalraj, Sunil, et al. Health literacy, communication, and treatment decision-making in older cancer patients. Oncology 15 Apr. 2009: 369. Academic OneFile. Web. 22 Oct. 2012.

Is Newer and More Expensive Care Better?

Sarah Miller, RN and Laura Covarrubias

Is more medical care really better? What about all these new, expensive drugs and high-tech surgeries? Do they save lives or improve health?

If you answered yes to these questions, you are not alone, but you may not be correct. A study done by the American Institutes for Research on insured adults between ages 18 and 64, found that most thought that more care, newer medical technology, and more expensive care were better. In addition, the adults interviewed believed that all care met minimum quality standards, and they were skeptical of evidence-based medical guidelines.

A typical response was “I don’t see how extra care could be harmful to your health. Care would only benefit you.” Although this belief is widely held, it is not accurate.  For example, if a healthy 80-year old man or woman without cancer symptoms is screened for various types of cancer, any abnormal findings are likely to result in treatment that is unlikely to benefit them.  That is why the U.S. Preventive Services Task Force usually recommends against screening 80-year olds for these cancers, although they recommend diagnostic testing for patients of all ages if they have symptoms.

“You get what you pay for” is another popular opinion, with many people assuming that more expensive care is superior. However, care that is far less expensive is sometimes just as good or even better.  One example of this is robotic prostatectomy, a surgery for men with prostate cancer that is done by a robot operated by the surgeon. Many men want this type of surgery, which costs $2,600 more than a regular prostate surgery. Some studies have shown that men who have the robotic surgery have lower rates of complications after the surgery, but others have shown that there is no difference. Most researchers who have conducted studies on this agree that the robotic surgery has not yet been proven to be any better than regular prostate surgery.

Even if robotic surgery isn’t worse than the regular surgery, is it worth the extra $2600? Consider this: for every two insured men that choose to have regular rather than robotic surgery, the cost savings could more than pay for one uninsured man with prostate cancer to have this life-saving surgery.[5] This is important to consider in the United States, where many people are not able to afford their medical care.

A similar idea that many patients have is “if it’s newer, it’s better.” While it may seem like new treatments would be chosen because they are better, this is rarely true. For example, cetuximab (also called Erbitux) was introduced in 2008 as a new addition to treatment for lung cancer patients. Although the drug was called a breakthrough in treatment for lung cancer, the average patient taking the drug lived only 1.2 months longer than patients not taking the drug. And in the many months of taking the drug, 85% of patients experienced skin toxicity, which often caused great discomfort (Fojo & Grady).  And despite the small possible advantages of the drug, it cost $80,000 for just a few months of treatment, resulting in huge medical bills that many families could not afford.  Avastin for Stage 4 breast cancer is an even more dramatic example.  Avastin is used for many cancers, but after several years, it became clear that on average, the breast cancer patients taking it were not living any longer and were more likely to have a stroke or other very serious and debilitating reaction to the drug that could make their last months much more painful physically and psychologically.

Cereal companies regularly add “New” in big letters on cereal boxes, because that sells more products (even if what is new might be a new toy inside).  Patients should be more cautious.  While some patients may want to take the chance that a new drug might be better, but many would rather know what the risks are before trying a new medication that could be worse than the tried and true treatments.

Evidence-Based Guidelines

Medical guidelines are usually established by a group that is considered expert in the subject of the guidelines. Medical guidelines are usually based on evidence from scientific research and are written according to the agreement a group of experts comes to about what the research tells them is the best for patients.

Unfortunately, research indicates that many adults are skeptical about guidelines.  Many seemed to think that asking providers to use guidelines did not allow them to make decisions based on their own expertise and that they could be used to ration care so that people did not “take” too much. One participant said that medical guidelines are “taking your choice away and putting it in someone else’s hands.”

Contrary to the mistaken belief that providers were restricted to actions dictated by the guidelines, in reality, guidelines are meant to guide providers by making suggestions based on the best evidence. Providers are still able to make the final recommendation to patients based on their professional expertise.

Is a doctor’s individual experience more valuable than guidelines?  That’s hard to say, but usually it would not be.  Guidelines are based on evidence from medical research comparing large groups of people who have had different types of treatment. Therefore, guidelines based on science will, on average, provide the best care for most people.  However, a physician with impressive expertise may be able to predict which patients are more likely to benefit from other types of treatment.

For example, for years, it was recommended that women between 40 and 69 years of age have a mammogram every year to screen for breast cancer. In 2007, however, the American College of Physicians changed their guidelines to leave it up to physicians to decide whether women between 40-50 needed annual mammograms.  In 2009, the US. Preventive Services Task Force wrote new guidelines, based on research evidence from thousands of women. The new guidelines recommended that women age 40-49 should not have regular mammograms to screen for breast cancer unless they had an especially high risk of breast cancer, and that women age 50-75 should have screening mammograms every two years – extending the age to older women but cutting the frequency from annually to every other year.

Many people challenged the new guidelines believing they could substantially delay the detection of cancer, especially for women under 50.  Isn’t it always better to have a chance to detect cancer earlier?

The answer is yes and no. Although mammograms save the lives of many women (including those in their 40’s), they also expose women to harmful radiation that can actually cause cancer over the course of women’s lifetimes. The researchers considered other forms of harm as well, such as the emotional trauma of a “false positive” results that result in stressful and expensive biopsies.  They concluded that the potential for harm outweighed the potential benefits of mammograms for the average women under age 50 and over 75, as did annual rather than biyearly mammograms for women age 50-75.

Many people did not agree with the U.S. Preventive Services Task Force’s interpretation of the evidence, however.  It is partly a matter of interpretation.  The U.S. Preventive Services Task Force was advising average women, and some cancer advocates believe that it is too difficult to predict whether a person is at high risk or not.  As a result, groups such as the American Cancer Society prefer to err on the side of over-treatment and radiation exposures, rather than on the side of potential under-treatment and reducing radiation exposure.

Health care providers are able to judge the two sets of guidelines and decide what to recommend for specific patients. For example, a woman in her 30’s who has many family members with breast cancer, including some at a young age, may be advised to have digital mammograms every other year in their 30’s (because they are more accurate than traditional mammograms and use less radiation) and annually after that.

“All care meets minimum quality standards” is another common belief.  Most could imagine providers making an occasional mistake, but few thought that there were any providers who consistently delivered a quality of care that did not meet basic standards.[1] Unfortunately, research shows that health care varies from doctor to doctor, and many do not meet minimum quality standards. The quality of care that doctors provide varies by the type of clinic where they work (publicly or privately funded, for instance), the communication skills of the doctor, and even how much sleep the doctor has been getting (Manusukhani; Kenny; Philipson).

What Can We Learn From This?

This study gives some insight into why we spend so much on health care and why efforts to improve medical care are often opposed as “rationing” or “death panels.” Unfortunately, most patients want the newest and most expensive care, and don’t understand that it may not be as safe or as effective as older, less expensive treatments.

In the United States, we spend more per person on health care than any other country, and yet our citizens are not as healthy as those in Japan, France, and Cuba, countries that spend far less per person on health care.

In addition to wasting money on treatments that are no better, and are sometimes inferior, our wasteful spending also means that we have less money for other essential services, such as education, housing, and national security.4

Of course, there is a lot of very expensive medical care that is medically necessary and could save a person’s life, such as trauma care in an emergency room for someone who has been in a serious car accident. But, there are also popular treatments that are expensive and not necessary, like a woman having labor induced for convenience when it would be safer and less expensive to have a natural birth. The key is to eliminate the unnecessary care so that we can continue to afford the necessary, beneficial care.

When it is not clear whether more expensive care actually helps or is just a waste of money, medical research can point us in the right direction. That’s why it is a good strategy to require “comparative effectiveness research” to determine whether, for example, robotic prostate surgery is better than regular surgery, or just needlessly more expensive.  It is often not obvious which treatments are the best, and sometimes they are the most expensive treatments but other times they may be the least expensive treatments or no treatment at all.

Doctors and patients can be part of improving medical care, by asking whether research conclusively shows which treatment is safer and which is most effective, instead of wrongly assuming that guidelines are aimed at saving money, not improving care.

References:

  1. Carman, KL; Maurer, M; Mathews, J; Dardess, P; McGee, J; Evers, M; & Marlo, KO, Evidence that consumers are skeptical about evidence-based health care, Health Affairs, 7 1400-6, 2010.
  2. Centers for disease control and prevention. Births: Final data for 2006, National Vital Statistics Reports.
  3. Caughney, AB; Sundaram, V; Kaimal, AJ; Cheng, YW; Geinger, A; Little, SE; Lee, JF; et.al. Maternal and Neonatal Outcomes of induction of labor. Evid Rep Technol Assess. 176 pp.1-257, 2009.
  4. Bodner-Adler, B; Bodner, K; Patiesky, N; Klimberger, O; Chalubinski, K; Mayerhofer, K; & Husslein, P; Influence of labor induction on obstetric outcomes in patients with prolonged pregnancy: A comparison between elective labor induction and spontaneous onset of labor beyond term. The Middle European Journal of Medicine. 117(7-8) pp. 287-92, 2005.
  5. Bolenz, C; Gupta, A; Hotze, T; Ho, R; Cadeddu, JA; Roehrborn, C; & Lotan, Y; Cost Comparison of Laproscopic, Robotic, and Open Radical Prostatectomy for Prostate Cancer, European Urology, 57 pp. 453-8, 2010.
  6. Lowrance, WT; Elkin, EB; Jacks, LM; Yee, DS; Jang, TL; Laudone, VP; Guillanneau, BD, Scardino, PT; & Eastham, JA, Comparative effectiveness of prostate cancer treatments: A population-based analysis of postoperative outcomes, The Journal of Urology, 183, 1366-72, 2010.
  7. Weizer, AZ; Strope, S; and Wood, DP, Margin control in laproscopic robotic prostatectomy: What are the REAL outcomes? Urologic Oncology: Seminars and Original Investigations, 28 pp.201-14, 2010.
  8. Barocas, DA; Salem, S; Kordan , Y; Herrell, SD; Chang, SS; Clark, PE; Davis, R; Baumgartner, R; Phillips, S; Cookson, MS; & Smith, JA, Robotic assisted laproscopic prostatectomy for clinically localized prostate cancer: Comparison of short-term biochemical recurrence-free survival, The Journal of Urology, 183, 990-6, 2010.
  9. Murphy, DC; Bjartell, A; Ficarra, V; Graefen, M; Haese, A; Montironi, R; Montorsi, F; Moul, JW; Novara, G; Sauter, G; Sulser, T; & van der Poel, H, Downsides of robot-assisted laproscopic prostatectomy: Limitations and complications. 57 pp. 735-46, 2009.
  10. Coelho, RF; Chauhan, S; Palmer, KJ; Rocco, B; Patel, MB; & Patel, VR, Robotic-assisted radical prostatectomy: A review of outcomes, British Journal of Urology International, 104, 1428-35, 2009.
  11. US Preventive Services Task Force, Screening for breast cancer: Recommendation statement 2009. Retrieved from: http://www.ahrq.gov/clinic/uspstf09/breastcancer/brcanrs.htm  on July 20, 2010.
  12. American Cancer Society, American Cancer Society Guidelines for the Early Detection of Cancer: Breast Cancer, 2010, Retrieved From: http://www.cancer.org/Healthy/FindCancerEarly/CancerScreeningGuidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer  on July 20, 2010.
  13. Smith, S; Newhouse, JP; & Freeland, MS; Income, insurance and technology: Why does health spending outpace economic growth? Health Affairs, 28(5) pp. 1276-84, 2009.
  14. Aaron, HJ and Ginsburg, PB; Is health spending excessive? If so, what can we do about it? Health Affairs