All posts by CPTFeditor

After Years of Complaints, U.S. and U.K. Officials Say They Want to Reform the Medical Device Industry

Amy Martyn, ConsumerAffairs: November 29, 2018.


The official who oversees medical device safety for the Food and Drug Administration (FDA) recently said he wants the United States to be the “first” to approve medical devices, raising concerns among public health advocates that the agency isn’t taking efforts to reform the device industry seriously enough.

Dr. Jeffrey Shuren, the director of the FDA’s medical devices division under both the Obama and Trump administrations, earlier this year agreed to speak at a conference attended by medical device executives, according to a new report by the Associated Press.

At the conference, which cost executives $1,000 a head to attend, Shuren reportedly said that the FDA’s goal was to be “first in the world” to approve new devices. He also said he wanted the agency to remove “unnecessary burdens” for companies hoping to get their devices approved.

Such a goal may be at odds with what public health advocates say is a need to reform medical device regulation. Dr. Peter Lurie, a former FDA official who now heads the watchdog the Center for Science in the Public Interest, told the Associated Press that Shuren’s comments essentially offered device executives “an invitation to a race to the bottom for scientific standards.”

“Fatally flawed” system

The medical device industry already faces lower barriers for approval than the drug industry does, despite the fact that many medical devices are intended to be permanent implants or can leave lifelong impacts on a person’s body.

“If you’re going to have something implanted in your body for potentially the rest of your life, wouldn’t you like it to be really well-tested beforehand? Is that really too much to ask?” Dr. Diana Zuckerman, a health policy analyst and head of the National Center of Health Research, told ConsumerAffairs earlier this year.

Independent researchers for years have said that the medical device approval process in the U.S. is “fatally flawed.”

More recently, a Netflix documentary called The Bleeding Edge exposed the tragic, life-long effects that four failed medical implants had on nearly 70 patients interviewed for the film.

Looking for improvement

Regulators in the United States and abroad are now promising to put safety at the forefront of medical device regulation.

Shortly before Thanksgiving, FDA Commissioner Scott Gottlieb, who was portrayed in the Netflix film as being in the industry’s pocket, announced new plans for the agency to “create a more robust medical device safety net for patients through better data.”

A similar call to reform medical device regulations is also currently taking place in Europe. In the United Kingdom, the Royal College Of Surgeons recently called for “drastic regulatory changes” after an investigative report by a group of European journalists published yesterday linked 83,000 deaths and 1.7 million injuries to faulty medical devices.

But while medical devices face low scrutiny from European regulators, the socialized healthcare systems abroad are at least more hesitant about allowing such devices to actually be used in surgery, experts say.

“In Europe, it’s very easy to get something on the market, but the national health plans won’t pay for it if it’s not proven to be safe and effective,” Zuckerman of the National Center for Health Research previously told ConsumerAffairs.

It’s not that Europeans aren’t reporting injuries from faulty devices. However, those who do tend to be wealthier people who opted for private insurance over the public plans.

See the original story here.

Here’s What We Know About Breast Implants and This Rare Type of Cancer

Daisy Melamed Sanders, Survivornet: November 2018.

A series of new stories are examining the potential health risks that both silicone- and saline-filled breast implants may carry. The most serious of these is the possibility of developing a type of blood cancer. What’s not yet clear is if the evidence is significant enough for the government to issue a warning.

The blood cancer that implants may cause, called Breast Implant-Associated Anaplastic Large Cell Lymphoma or BIA-ALCL, is a type of non-Hodgkins lymphoma that is not breast cancer. It is rare, and symptoms include pain, redness and swelling around the implant or breast area.

And while getting breast implants certainly does not definitively mean you’ll definitely get this type of lymphoma, it’s a dangerous illness for those who do get it. “ALCL is rare, but for those who get ALCL from their breast implants, it is very frightening and potentially fatal,” says Diana Zuckerman, PhD, President of the National Center for Health Research.

Here’s what we do know: The Food and Drug Administration—responsible for regulating medications and medical devices—has acknowledged that it has known of a potential relationship between breast implants and increased risk of ALCL since 2011. The risk involves both textured and smooth implants but the FDA’s position is that the textured kind may have a higher likelihood of causing the disease. The FDA also notes that incomplete or inefficient monitoring of, and reporting on, these health issues on a national level has meant that many women do not know all the facts when choosing to have implants for either cosmetic or reconstructive reasons.

According to the FDA, “In most cases, BIA-ALCL is found in the scar tissue and fluid near the implant, but in some cases, it can spread throughout the body. Precise risks are difficult to determine due to lack of information about how many patients have received breast implants in the US and worldwide.”

In an interview conducted prior to recent news, Dr. Andrea Pusic, Chief of Plastic Surgery at Brigham and Women’s Hospital, told SurvivorNet that breast implants are generally considered safe—but they do require monitoring by a doctor. The FDA also states that breast implants are “not lifetime devices,” and that the longer a patient has them, the more likely they are to rupture or experience other complications.

With regards to the safety of implants, Dr. Darrick Antell, a private practice plastic surgeon in New York City, cites the rarity of these instances as part of the reason implants are not excessively dangerous. “Textured surface implants have rarely been noted to develop ALCL, at a rate of 1 in 30,000—I would even recommend them to a family member,” he says. “Multiple leading institutions from around the world have shown them to be safe.”

But, as Dr. Zuckerman urges, it’s important to discuss the risk with your doctor before getting implants, because some women felt blindsided and uninformed about the disease possibility. “We know women who, when they developed ALCL, felt betrayed because their doctors hadn’t warned them of the risks.”

Breast implants also have the possibility of causing other health or physical issues. These issues have not been fully studied, but Zuckerman and the NCHR recently released a paper that discusses some of the possible side effects.

The risks that come with implants are real for all women, Dr. Zuckerman tells SurvivorNet, but these risks increase with a personal or family history of autoimmune or connective tissue symptoms or diseases. They can happen soon after getting implants or years later, and are especially likely when a silicone gel implant breaks—most likely after three years. Another issue is that leaking silicone can migrate into the lymph nodes, and, “from there, the silicone can get into the lungs, liver, or other organs.” Broken saline implants, she continues, offer less risk when they leak, but can cause health issues from the silicone shell, other chemicals, as well as from bacteria, fungus and mold issues that develop over time.

This isn’t the first time instance of concern regarding breast implants and potential health risks. Throughout the 1980’s and early 1990’s, a company called Dow Corning was named in a number of class-action lawsuits claiming that their breast implants were the cause of a number of health issues.

In 1992, the FDA mandated that silicone implants be removed from the market, but they were re-introduced in 2006 following stricter regulations around tracking patients for at least 10 years after their surgeries. However, because monitoring the implants and patients with them is not always thorough nor properly reported, it is difficult to know for sure what side effects implants are having in the long term.

The best idea, as always, is to discuss all the possible risks and benefits of implants with your doctor before any procedures, and be on alert for any symptoms that indicate a medical issue, suggests Dr. Zuckerman. “If a woman with implants starts to have any of the autoimmune symptoms that we’ve described in our report, she should consider having her implants removed.”

See the original story here.

Cervical Cancer Screening Options: What Is Best For You?

Jared Hirschfield & Varuna Srinivasan, MBBS, MPH, National Center for Health Research


Smiling womenCervical cancer is cancer in the cells lining the cervix, the narrow passage between the uterus and vagina. This cancer is usually diagnosed in women between the ages of 35 and 44.1 Each year in the United States, approximately 13,000 women are diagnosed with cervical cancer and 4,700 women die from cervical cancer.1With regular screening and follow-up, however, cervical cancer is one of the easiest cancers to prevent and is highly curable if found early.

Almost all cases of cervical cancer are caused by the human papillomavirus (HPV), most commonly by two high-risk strains called HPV-16 and HPV-18.2 However, nine out of ten HPV infections go away on their own without treatment and do not result in cancer or any other health problems.

In addition to exposure to HPV-16 and HPV-18, there are other factors that put you at an increased risk for cervical cancer, including:3

  1.     Smoking
  2.     Multiple sexual partners and sexual intercourse at an early age
  3.     Obesity
  4.     In utero exposure to DES, a hormonal medication banned by the FDA in 1975
  5.     Long-term use of oral contraceptive pills
  6.     Multiple pregnancies
  7.     Other sexually transmitted diseases, such as HIV and chlamydia
  8.     Poor dietary habits or low consumption of fruits and vegetables
  9.     Family history of cervical cancer

Screening for cervical cancer

There are three screening methods to help detect and diagnose cervical cancer early when it is easy to treat. These include Pap smears, HPV tests, and a combination of both Pap smears and HPV tests (cotesting).

The United States Preventive Services Task Force (USPSTF) is a group of experts that recently updated its recommendations for cervical cancer screening.  They recommend no screening for women under 21 and a Pap smear every three years for women 21-29 years old. For women between the ages of 30 and 65, they recommend a Pap smear every 3 years or a high-risk HPV (hrHPV) test every 5 years.  As an “alternative,” USPSTF recommends Pap smear-HPV cotesting every 5 years. They do not recommend any screening for women over 65 or women who have had a hysterectomy.4

USPSTF Cervical Cancer Screening Recommendations (Updated August 2018)4

Women younger than 21 years
  • No screening of any kind
Women aged 21 to 29 years
  • Pap smear alone every 3 years
Women aged 30 to 65 years Preferred:

  • Pap smear alone every 3 years
  • hrHPV testing alone every 5 years

Alternative:

  • Pap smear-hrHPV cotesting every 5 years
Women older than 65 years
  • No screening of any kind
Women who have had a hysterectomy*
  • No screening of any kind

*with removal of the cervix

What is a Pap smear?

A Pap smear is used to evaluate abnormal cells in the cervix that can be diagnosed as pre-cancer or as cervical cancer. When a woman undergoes a Pap smear, a doctor or nurse collects cells from the outer layer of the cervix with a special stick, swab or a soft brush. The sample is then sent to a lab, where a pathologist checks for signs of abnormal cells. If the test is “positive,” the woman has abnormal cells, and those are graded, from least severe to most severe, as ASC-US (atypical squamous cells of undetermined significance), LSIL (low-grade squamous intraepithelial lesion), ASC-H (atypical squamous cells, cannot rule out HSIL), or HSIL (high-grade squamous intraepithelial lesion). Based on this grade, your doctor might recommend further testing, such as a colposcopy (a procedure in which the cervix is examined with a magnifying instrument) or a cervical biopsy.

What is an hrHPV test?

In a high-risk HPV test, also known as an hrHPV test, cells collected from the cervix are tested for the presence of HPV-16 and HPV-18, types of HPV that are most likely to cause cervical cancer. Keep in mind, however, that unlike the Pap smear, the HPV test does not tell you whether you have cervical cancer or are likely to develop cervical cancer.  Instead, it can only tell you if you currently have the virus that can be dangerous now or in the future.2

Which screening test is better?

The goal of both screening tests is to detect cervical cancer as early as possible while keeping the risks to women at a minimum. Pap smears and HPV testing accomplish this in different ways. Whereas Pap smears identify abnormal cells currently in your body, HPV testing indirectly measures your risk of precancer or cancer by identifying the presence of the virus.  HPV testing itself is not harmful, but testing for a virus that usually goes away by itself can lead to a very high rate of false positives.5 This means that people who may never actually develop cervical cancer may undergo expensive and painful invasive procedures to test for cancer and will experience the stress and fear of a cancer diagnosis.

Women with more than one sexual partner in recent years or whose sexual partner has other sexual partners are especially likely to have HPV. For that reason, the National Center for Health Research (NCHR) recommends a Pap smear every 3 years rather than an hrHPV test for these women. Alternatively, NCHR recommends combining a Pap smear and hrHPV test every 5 years.  In addition, we recommend that women over 65 who have recently had more than one sexual partner or have had a sexual partner who has had other sexual partners should continue regular Pap smears until age 75.

Bottom line: What is the best screening option for screening and how can cervical cancer be prevented?

The USPSTF recommendations are based on assumptions about the sexual activity of women at different ages. On average, women over 30 tend to have fewer sexual partners and more monogamous relationships than women under 30, and women over 65 have even fewer.  However, the National Center for Health Research recommendation is focused more on the number of sexual partners, and the fact that women in a monogamous relationship do not necessarily know if their sexual partner has had any other sexual partners. For that reason, we recommend Pap smears every 3 years or Pap smear-hrHPV cotesting every 5 years as the preferred methods of cervical cancer screening for most sexually active women aged 30 to 75. Pap smears directly determine the presence of cancerous or precancerous cells in your body. Cotesting can provide the added benefit of identifying high-risk HPV infection and allow for more vigilant follow-up if HPV-16 or HPV-18 is diagnosed.

In addition to monogamous relationships, women can reduce their chances of cervical cancer by using condoms. Other ways of reducing the risk include regular screening and follow-up with your physician, exercising, maintaining a healthy weight and balanced diet, and avoiding tobacco products.

 

[1] American Cancer Society. “Key Statistics for Cervical Cancer.” 04 January 2018. https://www.cancer.org/cancer/cervical-cancer/about/key-statistics.html.

[2] Centers for Disease Control. “Cervical Cancer.” December 2016. https://www.cdc.gov/cancer/cervical/pdf/cervical_facts.pdf.

[3] American Cancer Society, What Are the Risk Factors for Cervical Cancer?, www.cancer.org, https://www.cancer.org/cancer/cervical-cancer/causes-risks-prevention/risk-factors.html, October 3rd 2018

[4] US Preventive Services Task Force. “Screening for Cervical Cancer US Preventive Services Task Force Recommendation Statement.” JAMA2018;320(7):674–686. doi:10.1001/jama.2018.10897

[5] Rebolj, M. et al. “The Problem of False-Positive Human Papillomavirus DNA Tests in Cervical Screening.” Current Pharmaceutical Design(2013) 19: 1439. https://doi.org/10.2174/1381612811319080011

The Dangers of Juuling

John-Anthony Fraga, National Center for Health Research


What is Juuling? Is it safer than smoking?

A new type of e-cigarette called “juul” has become so popular that it is now about 68% of the $2 billion e-cigarette market. The “juul” is especially popular among children and young adults due to its sleek and discreet design, its ability to be recharged on a laptop or wall charger within one hour, and its liquid-filled cartridges that come in popular flavors like cool mint, creme brulee, and fruit medley.

As a result, “juuling” is now very common at teenage hangouts and even at school. Medical professionals are very concerned because juul delivers higher concentrations of nicotine than other e-cigarettes. Not only is nicotine highly addictive, but it is also toxic to fetuses and is known to impair brain and lung development if used during adolescence.[1] It is not replacing cigarette smoking but rather encouraging it: A 2017 study found that non-smoking adults were four times more likely to start smoking traditional cigarettes after only 18 months of vaping, which includes “juuling.”[7] For more information about e-cigarettes in general, check out our article here.

How does the Juul Work?

According to Juul Labs, the company that owns and sells the juul e-cigarette, the device uses an internal, regulated heating mechanism that creates an easily inhaled aerosol. This mechanism prevents the batteries in the juul from overheating and exploding, which has been a problem for other brands of e-cigarettes. Juul is easy to use because there are no settings to adjust or control. All that is required is a non-refillable juul pod cartridge that clicks into the top of the juul and contains a nicotine e-liquid formula. This e-liquid is heated and converted into vapors that are inhaled by the user. One of the reasons it is so popular among youth is that it is so easy to use – no prior experience or knowledge required. All they have to do to intake nicotine is to put a juul to their mouth and inhale.

What makes Juuls different from other e-cigarettes?

The increased harm of juuls compared to other e-cigarettes is due to the concentration and contents of its juul pods. The e-liquid is 5% nicotine by volume, which is more than twice the concentration of nicotine in similar devices like the Blu e-cig cartridge (2.4% nicotine). This increases the risk of addiction; in fact, a study done by the UK’s Royal College of Psychiatrists showed that nicotine is about as addictive as cocaine and even more addictive than alcohol and barbiturates (anti-anxiety drugs).[2]

The impact on the developing brain is also of great concern. Brain imaging studies of adolescents who began smoking at a young age had markedly reduced activity in the prefrontal cortex of the brain, an area critical for a person’s cognitive behavior and decision making, leading to increased sensitivity to other drugs and greater impulsivity.[3] The amount of nicotine in one juul pod is equivalent to a pack of cigarettes. Since teens often use multiple pods in one sitting, they can unknowingly become exposed to unsafe levels of nicotine that can have immediate and long-term health consequences. In 2016, the Food and Drug Administration (FDA) was given the authority to regulate e-cigarettes such as juul but has allowed e-cigarette manufacturers to postpone their applications for FDA approval until August 2022. Meanwhile, these harmful devices can remain on the market and continue influencing adolescents to become addicted to nicotine.[8]

Another reason why the juul is a unique threat to teens is its patented formula of nicotine. While other brands use a chemically modified form called “freebase nicotine,” juuls use “nicotine salts” that more closely resemble the natural structure of nicotine found in tobacco leaves. This makes the nicotine more readily absorbed into the bloodstream and makes the vapor less harsh so that it is easier to inhale more nicotine for longer periods of time.

In addition to this patented formula, juul pods contain a greater amount of benzoic acid, 44.8 mg/mL, compared to other e-cigarette brands, which are in the range of 0.2 to 2 mg/mL. According to the Center for Disease Control and Prevention (CDC), benzoic acid is known to cause coughs, sore throat, abdominal pain, nausea, and vomiting if exposure is constant, which is the case when using a juul.[4] This is due to how juuls utilize the properties of benzoic acid to increase the potency of the nicotine salts in its e-liquid.

What makes Juuls popular among children and teens?

Since juuls are small, discreet, and closely resemble a USB drive, they can be easily hidden and used in a wide variety of settings, such as the classroom. Teachers and school administrators across the nation are finding students juuling when their backs are turned: Students can take a hit, blow the small, odorless puff of smoke into their jacket or backpack, and continue their school work in a matter of seconds. Compared to other forms of teenage rebellion, juuling is especially dangerous as middle and high school students are unknowingly becoming addicted to nicotine at an alarming rate.

Because a person must be at least 21 to purchase a juul or juul pod, a juul black market is the source for many teens, through eBay or Craigslist. In response, the FDA contacted eBay to raise concerns about listings of juul products on its website, resulting in the removal of the listings and the creation of measures to prevent new listings from being posted.[5]

In April 2018, FDA Commissioner Scott Gottlieb announced that he was creating a Youth Tobacco Prevention Plan aimed at stopping the dramatic rise in the use of e-cigarette and tobacco products among youth. The FDA specifically asked Juul Labs for documents related to product marketing and research on the health, toxicological, behavioral, or physiological effects of their products in order to understand why youth are so attracted to them.[6] Additionally, Juul Labs is currently facing lawsuits in several states claiming that its products were deceptively marketed to youth under the legal smoking age. The FDA now plans to create enforcement policies for e-cigarette manufacturers, including juul, that are marketing their products to children and teenagers.

The Bottom Line:

The popularity of juuls among adolescents exposes them to large amounts of nicotine that can have adverse health risks for their physical and emotional development. While juuls are called e-cigarettes, they look nothing like them, making it easy for children and teens to secretly use them without a parent, guardian, or teacher noticing. This may be just a temporary trend, but if the FDA does not quickly do more to restrict flavors that appeal to adolescents and to educate the public about the risks, it is likely to create an enormous increase in young people addicted to nicotine.

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

References:

  1. England, L., Bunnell, R., F. Pechacek, T., Tong, V., & A. McAfee, T. (2015). Nicotine and the Developing Human (Vol. 49).
  2. Nutt, D., King, L. A., Saulsbury, W., & Blakemore, C. (2007). Development of a rational scale to assess the harm of drugs of potential misuse. The Lancet, 369(9566), 1047-1053. doi:https://doi.org/10.1016/S0140-6736(07)60464-4
  3. Musso, F., Bettermann, F., Vucurevic, G., Stoeter, P., Konrad, A., & Winterer, G. (2007). Smoking impacts on prefrontal attentional network function in young adult brains. Psychopharmacology, 191(1), 159-169. doi:10.1007/s00213-006-0499-8
  4. Centers for Disease Control and Prevention. Safety Material Data Sheet: Benzoic Acid. Accessed July 30, 2018. Available at: https://www.cdc.gov/niosh/ipcsneng/neng0103.html
  5. “Statement from FDA Commissioner Scott Gottlieb, M.D., on new enforcement actions and a Youth Tobacco Prevention Plan to stop the youth use of, and access to, JUUL and other e-cigarettes. ” FDA News & Event. FDA, April 24, 2018. Accessed: July 30, 2018. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm605432.htm
  6. “Official Request of Information for JUUL Labs.” FDA Rules and Regulations, FDA. April 24, 2018. Accessed: July 30, 2018. https://www.fda.gov/downloads/TobaccoProducts/Labeling/RulesRegulationsGuidance/UCM605490.pdf
  7. Primack, B. A., Shensa, A., Sidani, J. E., Hoffman, B. L., Soneji, S., Sargent, J. D., . . . Fine, M. J. (2018). Initiation of Traditional Cigarette Smoking after Electronic Cigarette Use Among Tobacco-Naïve US Young Adults. The American Journal of Medicine, 131(4), 443.e441-443.e449. doi:10.1016/j.amjmed.2017.11.005
  8. “FDA’s Comprehensive Plan for Tobacco and Nicotine Regulation” FDA Newsroom, FDA. August 6, 2018. Accessed: August 8, 2018. https://www.fda.gov/TobaccoProducts/NewsEvents/ucm568425.htm

Buy a Nice Sleep Mask! It’s an Investment in your Health

Jessica Becker, Cancer Prevention and Treatment Fund

Research shows that sleeping in total darkness allows your body to produce as much of the hormone melatonin as possible. This is good because when your production of melatonin drops, you are at greater risk of breast and/or colorectal cancer and other health risks.

What is Melatonin?

Melatonin is a hormone that is naturally produced in your body. It is secreted by the pineal gland, which is buried deep in the brain. Melatonin is only produced at night and only when it is dark, which means that melatonin production peaks between 3:00 a.m. and 5:00 a.m. for most people. This hormone helps to regulate your circadian rhythm, which is like your body’s natural clock. When melatonin and several other chemicals are released, you feel drowsy and your body temperature lowers. In addition to this sleep-cycle function, melatonin also works as an antioxidant. This means that it can help prevent damage to your DNA that can result from aging, exposure to cancer-causing chemicals, or harmful rays from the sun. Preventing damage to DNA is important because DNA damage can cause cancer.

Doesn’t My Body Produce Enough Melatonin?

There have been major advancements in technology over the last two centuries, one being the light bulb. Because of the light bulb (and electricity, in general), we are able to stay awake and active much later, so the night is not as dark as it used to be. Think of New York City: the city that never sleeps. Cities are so lit up at night that it can be hard to see the stars. This is referred to as “light pollution.” And, of course, even in the middle of nowhere, you can keep your lights on all night in your house.

Our ability to turn night into day has allowed for more night shift work, often called “the graveyard shift.” Even if you don’t work on the late shift, you may be working at home late at night or staying up late watching TV or using the internet. Unfortunately, this kind of schedule has many effects on your body, including reducing the amount of melatonin produced. But it is not just night owls or shift workers who suffer from a decreased production of melatonin. Sleep studies show that almost everyone wakes up at some point during the night, even if we do not remember it. Unless you have blackout shades on your windows, there is a good chance that some light is coming into your bedroom and that your eyes are registering this light during those wakeful periods.[2]

New technology is compounding the effects of light pollution. Early incandescent light bulbs that were dim and yellow and did not affect melatonin production very much. Now, artificial light emits more blue wavelengths. For example “Cool White” fluorescent bulbs are a very popular choice of light bulb because they are bright, moderately energy efficient, and relatively inexpensive. They also produce a lot of blue light which is why they have a “cool” effect. Maybe you have noticed while driving that certain people’s headlights appear to be very bright and have a blue tint to them. These new headlights produce blue wavelengths of light. Unfortunately, research shows that blue wavelengths of light are especially effective at reducing melatonin production in humans.[3] All types of computer monitors and television screens also emit blue light.

Why Is Having Less Melatonin A Bad Thing?

Believe it or not, the International Agency for Research on Cancer (IRAC) classified shift work as a probable human carcinogen in 2007. There have been numerous studies showing a link between night shift work and an increased incidence of breast cancer. For instance, a study done in the Netherlands found that by working half a year at night, a person’s risk of breast cancer increased 150%.[3] A major study found that nurses who worked night shifts at least 3 times a month for 15 years or more had a 35% increased risk of colorectal cancer.[3] If you’re still unconvinced, a study conducted in 147 communities in Israel found that women who lived in neighborhoods where it was bright enough to read a book outside at midnight had a 73% higher risk of developing breast cancer than women living in areas without outdoor lighting.[2]

What Can I Do To Limit My Chances Of Getting Cancer Because of Light At Night?

The good news is that there are easy and inexpensive ways to limit the amount of light you are exposed to at night. For starters, if you have electronic appliances in your bedroom that produce light (like a clock radio or cable box), pick those that have red lights as opposed to green or blue lights. Walmart, Target, Best Buy, and many other stores all carry alarm clocks and radios that display the time in red numbers. These brands are not more expensive than their blue numbered counter-parts. Studies show that red lights don’t cause as much of a decrease in the amount of melatonin produced by your body.[4] Also, if you have a television or computer in your bedroom, turn it off before you go to sleep.

It is also a good idea to limit the amount of time you spend in front of a screen at night. If you spend a few hours a night in front of your computer, whether or not you’re not in your bedroom, you are decreasing the amount of melatonin that is being produced in your brain. Most screens today offer a “night mode” which reduces the amount of blue light used and creates an orange tint. This is a recommended setting to use before bed.

Also, since melatonin production is highest between the hours of 3:00 am and 5:00 am, make sure you’re in bed and asleep by 3:00 a.m., and if at all possible, sleep until at least 5:00 am. While you probably will not be able to petition your community to get the street light in front of your house turned off, you can buy blackout shades to block the light. Most department stores sell blackout shades, and they are relatively inexpensive. If you don’t want to invest a penny more in “window treatments,” consider using a sleep mask. Airlines sometimes give them away in travel kits, but you can also treat yourself to a nice one that is sold online or in a department store. Besides lowering the risk of getting certain cancers, sleep masks can also lower your stress and help you fall asleep faster. Now that’s a “three-for!”

All articles on our website have been approved by Dr. Diana Zuckerman and other senior staff.

  1. Navara J, Nelson R. The Dark Side Of Light At Night: Physiological, Epidemiological, and ecological consequences. Journal of Pineal Research. 2007, (43)
  2. Chepesiuk R. Missing the Dark: Health Effects of Light Pollution. Environmental Health Perspectives. 2009, (117)
  3. Pauley S. Lighting For The Human Circadian Clock: Recent Research Indicated That Lighting Has Become A Public Health Issue. Medical Hypotheses. 2003
  4. Reiter R. Circadian Disruption and Cancer: Making the Connection. The New York Academy of Sciences. 2009

DCIS, LCIS, and other Pre-Cancers: Are Women Getting Mastectomies They Don’t Need?

Susan Dudley, PhD and Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund

Thanks to heightened awareness of breast cancer screening, women are being diagnosed earlier than ever before. However, that has also resulted in what some experts consider an epidemic of women diagnosed with abnormal breast conditions that are not cancer or may never develop into invasive cancer. Some of these conditions are not at all dangerous, and the others have survival rates near 99%; nevertheless, these diagnoses often sound very frightening. In fact, research shows that these women are often just as worried about whether they will survive as women with the much more dangerous, invasive forms of breast cancer.

There is a wide range of treatment for women with these “stage zero” conditions. Although mastectomies are almost never necessary or recommended by experts, many women undergo mastectomies nevertheless. Research suggests that this is especially likely in the South, Midwest, and Southwest parts of the United States, in certain types of medical facilities, and with older doctors.

Knowing the Facts Will Reduce the Fear

It can be extremely upsetting for a woman to learn that she has any condition that increases her breast cancer risk. Too often, such news leaves women feeling that they must rush into surgery. They agree to – or even insist upon – undergoing mastectomies that they do not really need, in hopes that it will increase their chances of survival. In fact, their chances of survival are already very high, and having a mastectomy will not make it higher.

The good news is that most women with “pre-cancerous” conditions or other non-cancerous breast conditions will never get invasive breast cancer. For example, only 1 in 12 breast lumps is cancerous, and 1 in 5 cases of micro-calcification (white spots seen on mammograms that alert doctors that follow-up diagnosis is needed) are related to cancer, so most women get good news after a breast biopsy. For many women, however, anxiety levels soar when they learn that they might possibly be at risk for breast cancer because of abnormal changes in their breasts.

This issue brief will describe two conditions that are often referred to as “stage zero breast cancer” as well as other non-cancerous abnormal breast conditions.

Ductal Cancinoma in Situ (DCIS)

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.” It is a non-invasive breast cancer 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 invasive cancer in the future if it is not treated. That is why surgical removal of the abnormal cells, followed by radiation, is usually recommended.

What makes most cancers dangerous is that they are invasive, which means they are not restricted to one spot, but have spread to other cells within the organ where they arose. Once that happens, cancer can metastasize, which means that it spreads to other organs in the body. DCIS is not an invasive type of cancer and DCIS can not metastasize unless it first develops into invasive cancer.

The goal of treating invasive cancer while it is still confined to the breast 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 an early-stage invasive cancer (usually called Stage 1 or Stage 2 cancer).

Having DCIS means that a woman has an increased risk for developing invasive breast cancer in the future, unless she has treatment. With appropriate treatment, DCIS is unlikely to develop into invasive cancer. A woman with DCIS does not need all the same treatment as a woman diagnosed with invasive breast cancer, but she does need surgery to remove the DCIS, and radiation to ensure that any stray, abnormal cells are destroyed. This lowers the risk that the DCIS will recur or that invasive breast cancer will develop.

DCIS does not need to be treated immediately. A woman can spend a few weeks after her diagnosis to talk with her doctors, learn the facts about her treatment choices, and think about what is important to her before she chooses which kind of treatment to have.

Treatment Choices for DCIS

DCIS patients have three surgery choices. They are 1) lumpectomy followed by radiation therapy 2) mastectomy or 3) mastectomy with breast reconstruction surgery. Most women with DCIS can choose lumpectomy.

Lumpectomy means that the surgeon removes only the cancer and some normal tissue around it. This kind of surgery keeps a woman’s breast intact – looking a lot like it did before surgery. Under most circumstances, mastectomy does not increase survival time for women with DCIS, and would only be considered under unusual circumstances, such as cases where the breast is very small or the area of DCIS is very large.

Radiation therapy is also recommended for almost all women with DCIS after lumpectomy. This type of treatment is very important because it could keep more DCIS or invasive cancer from developing in the same breast. DCIS patients who choose lumpectomy with radiation live just as long as they would with mastectomy.

Tamoxifen or another hormonal therapy is recommended for some women with DCIS to help prevent breast cancer. The benefit is that it can further decrease the risk of recurrence of DCIS or the development of invasive breast cancer. However, these medicines can have potentially dangerous side effects, such as increased risk of endometrial cancer, severe circulatory problems, or stroke. In addition, hot flashes, vaginal dryness, abnormal vaginal bleeding, and a possibility of premature menopause are common for women who were not yet menopausal when they started treatment.

Unlike women with invasive breast cancer, women with DCIS do not undergo chemotherapy and they usually do not need to have their lymph nodes tested or removed. Experts are not sure whether all women with DCIS would eventually develop invasive breast cancer if they live for a long time and are not treated. They do know that most women with DCIS who undergo surgery and radiation can put fears of breast cancer behind them.

Lobular Carcinoma in Situ (LCIS)

Lobular carcinoma in situ (LCIS) is also sometimes referred to as stage zero breast cancer. But we shouldn’t let the words “carcinoma” or “cancer” scare women. LCIS got its name many years ago, before doctors realized that it is not breast cancer at all.

Unlike breast cancer, LCIS does not form a tumor. Unlike DCIS, it does not form abnormal cells that can develop into invasive cancer. That is why no surgery is needed to remove LCIS. Instead, LCIS is one of several conditions that may indicate an increased risk for a woman to develop breast cancer in the future. Even though most women who have LCIS never develop breast cancer, a woman with LCIS should talk to her physician to evaluate all her risk factors and to set up a plan to monitor her breast health, such as regular mammograms. This will ensure that any changes in her breast health can be detected and evaluated very early.

How is LCIS different from breast cancer?
In LCIS, some of the cells lining the lobules (the parts of the breast that can make milk) have developed abnormally. LCIS is not cancer. It does not cause pain or produce a lump. In fact, by itself, LCIS is not a dangerous condition.

How does LCIS affect breast cancer risk?
There is no way for doctors to predict whether a woman with LCIS will develop breast cancer in the future. Most won’t, but if they do, it could be in either breast (not just the one where the LCIS was found) and in any part of the breast (not just in the area near where the LCIS was discovered).

What is the treatment for LCIS?

LCIS has no symptoms, and is first suspected because of an abnormal mammogram. A biopsy is needed to confirm the diagnosis. After a diagnosis is made, no more surgery or other treatment is needed, even if the affected area is large.

The abnormally developing cells that make up LCIS are often spread around in more than one location in the breast. It may even be in several areas and both breasts. If LCIS is diagnosed in one breast, it is not necessary to search for it or biopsy the second breast or to try to locate each area of affected lobules. That’s because no treatment is necessary regardless of the spread or location.

Women diagnosed with LCIS may question why no treatment is necessary, but experts agree that LCIS is a condition that should be managed rather than a disease to be treated. You can think of it like being overweight, which is a condition that puts a person at risk for heart disease but is not itself heart disease – and people who are overweight do not always develop heart disease.

Women with LCIS who are especially worried and want to “do something” can consider a low calorie or low-fat diet, as well as an increase in fresh fruits and vegetables to reduce their risk of future breast cancer. Although the research is not conclusive, those kinds of dietary changes may reduce the risk of breast cancer, and also have the potential to prevent other diseases. Hormonal therapy (with a drug such as tamoxifen) is also sometimes recommended to reduce the risk of future breast cancer, although it has the potentially dangerous side effects mentioned earlier, such as increasing the risk of stroke and endometrial cancer, and can cause unpleasant symptoms such as hot flashes and vaginal dryness. However, if a woman is very worried and does not feel comfortable without treatment, hormonal therapy is a less radical prevention method that bilateral mastectomies.

Other Non-Cancerous Breast Conditions.

Many women who find lumps on their breasts do not have cancer, DCIS, or LCIS. Non-cancerous lumps can be cysts that are filled with fluid, or fibroadenomas, which are smooth, and hard, often feeling like a marble under the skin. Thickened but harmless areas called pseudo-lumps also fall into this category. Cysts are sometimes but not always drained, but otherwise, these conditions usually require no further treatment. Fibrocystic breasts (also called mammary dysplasia, benign breast disease, or diffuse cystic mastopathy) feel bumpy or lumpy and sometimes painful. This condition used to be considered a pre-cancerous disease, but experts now realize that it is not a disease and does not increase the risk of breast cancer.

What About Mastectomy to Prevent Future Breast Cancer?

Ten or 20 years ago, when breast conditions like these were diagnosed, they were often treated with mastectomy, surgery which completely removes the affected breast. Sometimes a healthy second breast was also removed (prophylactic mastectomy), even when there was no sign of cancer or other abnormalities in the other breast.

Today, thanks to advances in scientists’ understanding of breast cancer and of these other conditions, along with the development of better diagnostic, surgical, and treatment techniques, mastectomy is often unnecessary. In fact, we now know that a less radical treatment (lumpectomy followed by radiation therapy for most DCIS or Stage 1 or Stage 2 cancers) or no treatment (for cysts, fibroadenomas, fibrocystic breasts, and LCIS) is just as effective. Except in unusual circumstances, mastectomy does not increase survival time for these conditions, and the risks of mastectomy usually outweigh any benefits.

Mastectomies to Prevent Cancer

Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund

Every year, thousands of women choose to undergo a mastectomy when lumpectomy would be an equally effective option for them. Some women choose a bilateral mastectomy when there is cancer in only one breast. Even women who do not have breast cancer may undergo mastectomies as a preventive measure because of their high risk of breast cancer.

Helping patients make an informed decision about whether to have a mastectomy is an important aspect of the physician-patient relationship. Unfortunately, many patients are not able to get the information they need from their physicians. A patient who is seriously considering a mastectomy or bilateral mastectomy that is not medically necessary may be basing her decision more on fear than on information. They may benefit from unbiased information, counseling, or from a second opinion before making a final decision.

The purpose of this article is to provide information that patients and family members can use to help them discuss their options with their physicians.

Gene Mutations that Increase the Risk of Breast Cancer (BRCA1 and BRCA2)

Women with known mutations in the BRCA1 and BRCA2 genes have a lifetime risk of breast cancer ranging from 40% to 85%, compared to 12% for women in the general population.1 Women with BRCA1 or BRCA2 mutations often develop breast cancer before age 50 and have a high risk of bilateral breast cancer and ovarian cancer.2 Removing breasts with no sign of cancer is called a prophylactic (preventive) mastectomy. Prophylactic mastectomy and prophylactic oophorectomy (removal of the ovaries) have both been shown to greatly reduce—but not eliminate—the risk of breast cancer in BRCA mutation carriers.1

Among women with strong family histories of breast cancer, individuals of Ashkenazi Jewish descent have an 8 times greater frequency of carrying these mutations in BRCA1 or BRCA2 compared with other women.3

Lumpectomy with radiation therapy is just as effective for preventing in-breast tumor recurrence in patients with BRCA mutations as it is for other women. Questions remain, however, about how other adjuvant treatments (such as chemotherapy) affect survival of women with these gene mutations.4

For women with the BRCA1 or BRCA2 genes, it is important to remember that the risk of breast cancer in the next 5 or 10 years is much lower than the lifetime risk of breast cancer. For example, the risk of breast cancer in her 20’s is very low, even with BRCA1 (less than 3%) or BRCA2 (approximately 1%). For a 30-year old woman, the risk by age 39 is higher (10% for women with BRCA1 and 8% for BRCA2). For a 40-year-old woman, the risk by age 49 is 16% for women with BRCA1 and 13% for women with BRCA2.3 Although these 10-year risk levels are much higher than for most women, they are much lower than the life-time risk that is so frightening. It is also important to remember that cancer treatments and prevention strategies are improving, so the risks of cancer may decrease and the survival rates are improving.

Non-Surgical Alternatives to Prophylactic Mastectomies

Many women who are at high risk for breast cancer consider having a prophylactic mastectomy to reduce their future cancer risk. Prophylactic mastectomies can prevent breast cancer, but many women who undergo prophylactic mastectomies would never have developed breast cancer, even without the surgery.

This is a decision that women need to make for themselves, but to make that decision they need a clear understanding of the risks and benefits as well as alternative strategies that also reduce risk.

Tamoxifen and raloxifene have both been shown to reduce the risk of breast cancer for women who have not had cancer but are at greater risk. However, it is not yet known if these drugs can prevent breast cancer for women with BRCA1 or BRCA2 mutations.

For women at high risk of breast cancer for any reason, mammography screening at a young age and annual breast MRIs are alternatives to prophylactic mastectomy. MRIs are more accurate than mammograms for young women and women with dense breast tissue.

Research indicates that a low-fat diet, weight control, and exercise may reduce the risk of breast cancer for all women, including women at high risk and women who previously were treated for breast cancer.4, 5

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

References

1 Schrag D, Kuntz KM, Garber JE, Weeks JC. Decision analysis – effects of prophylactic mastectomy and oophorectomy on life expectancy among women with BRCA1 or BRCA2 mutations. New England Journal of Medicine. 1997;337(6):434.

2 Rubinstein, WS. Hereditary breast cancer in Jews. Familial Cancer. 2004;3:249-257.

3 Chen S, Iversen ES, Friebel T, Finkelstein D, Weber BL, Eisen A. et al. Characterization of BRCA 1 and BRCA 2 mutations in a large United States sample. Journal of Clinical Oncology. 2006;24(6):863-869.

4 Breast Cancer (PDQ®): Treatment. National Cancer Institute. http://www.cancer.gov/cancertopics/pdq/treatment/breast/HealthProfessional/

5 Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, et al., The women’s health initiative randomized controlled dietary modification trial. JAMA. 2006;295(6):629-642

Should I “Upgrade” to Digital or 3D? A Mammography Guide

Christina Silcox, PhD, and Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Woman_receives_mammogram

When breast cancer is detected early—before it has spread—it is easier to treat and women have a much better chance of living a long life.  Screening refers to tests that are given to people who have no symptoms, to find out if they might have a disease.  Mammograms are the best way to screen women for breast cancer.

Forty million mammograms are performed each year,2 but the technology is evolving. Depending on where a woman lives, she may be able to choose from among three different types of mammography. Does it matter what kind of mammogram she gets?

A New Type of Digital Test: 3D Mammography

3D mammograms, also known as tomosynthesis or “tomo,” use the same x-ray technology as regular “2D” mammograms. The procedure is the same from the patient’s point-of-view, although it will take a few seconds longer. In both 3D and 2D mammograms, the breast is compressed between two plates. In 2D mammograms, which take images only from the front and side, this may create images with overlapping breast tissue. Because 3D mammography provides images of the breast in “slices” from many different angles, finding abnormalities and determining which abnormalities seem potentially worrisome may be easier with 3D tests. On the other hand, 3D mammography is more expensive than 2D, and your insurance may charge you more if you use 3D.

Since 2013, the FDA has concluded that a low-dose 3D digital mammography is at least as accurate as 2D mammography. 2D digital images can also be obtained from the 3D mammography data.

Differences between 2D and 3D Mammograms

Because it was initially not known how accurate 3D mammograms would be, most research compared 2D mammograms to a combination of 3D mammograms and 2D mammograms.  That was the information that Hologic, the company that developed the first 3D mammography machines, needed to provide to the FDA when they applied for FDA approval.  The studies were funded by Hologic and evaluated the mammograms from their machines.  We do not know if the results would be similar to other companies’ mammography machines.

The results of the studies showed that the combination of 3D and 2D was more accurate than 2D digital or film mammograms, although the difference in accuracy was tiny for each patient.6,7,8,9,10,11  In addition, women who undergo screening with 3D+2D mammography are less likely to be called back for more testing due to a suspicious finding that turns out not to be cancer. This means fewer false alarms caused by inaccurate findings.7,8,12  But, using two tests is not practical and can be harmful because it exposes women to more radiation. The important question is: Do the 3D tests hold up on their own?

An article published in 2017 in the prestigious medical journal JAMA examined the benefits of 3D mammograms. The study compared the number of call backs and the numbers of cancers diagnosed before the next scheduled screening in women who had 3D mammograms vs. standard 2D mammograms. For the more than 23,000 women undergoing an initial 2D mammogram followed by 3 years of annual 3D mammograms, the use of 3D tests slightly reduced the number of women who got called back (10% in the 2D group vs. 9% in the 3D group) and the number of cancers detected in the months between the annual mammograms. Following 2D mammography, about 7 out of 10,000 women were diagnosed with cancer before their next annual mammography, compared to 5 out of 10,000 of the women who underwent 3D mammography screening.[16]  Although the differences are very small, they are statistically significant, which means they did not happen by chance.

Even though the differences are small, 3D tests seem to have a small advantage over 2D tests because they are slightly better at finding dangerous cancers, reducing the number of repeat tests, and reducing the amount of time a woman has to wait to find out.

While the benefits of 3D mammograms appear to be tiny for an individual woman, the benefits of the 3D test could add up for a large population of women.  For example, a study examining over 44,000 screening tests, including over 28,000 3D mammograms, over 5 years found that 3D screening detected significantly smaller invasive breast cancers (about 1.5 cm (about ½ inch) vs. 2.3 cm (about 1 inch). And, the cancers that were detected by 3D tests were less likely to have spread to the lymph nodes (about 15% vs. 31%).[17] Finding a cancer that is smaller and hasn’t spread to the lymph nodes means that a woman would require less aggressive treatment of her cancer, such as less radical surgery and fewer chances of needing chemotherapy.

Even if 3D mammography is more accurate, does it save lives?

Experts used to believe that mammograms reduced breast cancer deaths by about 14% to 32%, based on very old studies.  Newer studies conclude that screening mammography has a smaller impact, decreasing breast cancer deaths by about 2%.[19] It is important to keep in mind that these studies include data up to the year 2005 when it was common practice to recommend mammograms every year. Experts now recommend screening be done every 2 years for women of average risk and believe it will not increase the percentage of women dying from breast cancer, but we don’t yet know exactly what impact this new screening practice will have.

Why would mammography save fewer lives today than in previous years?  It may be because cancer treatments have gotten better, even for more advanced cancers. Also, as mammography has improved, it is detecting abnormalities and cancers that may not be fatal. Even if 3D mammograms can detect invasive cancers when they are smaller and less dangerous, more research is needed to determine if 3D mammography saves more lives.

Harms of 3D screening:

Radiation exposure

The 3D test takes a few seconds longer than 2D digital or film mammography (adding a few seconds of discomfort). The newer, low-dose 3D mammography uses less radiation than a 2D mammography.

Because digital mammography—2D and 3D—is relatively new, no one has figured out exactly what all the health risks and benefits are.

Cost

2D screening mammograms are free for patients covered by healthcare insurance under the Affordable Care Act. Some insurers will not cover 3D mammograms, and others charge women a surcharge. However, Medicare began covering 3D mammography in 2015 and some states are beginning to mandate coverage.13

The Bottom Line

On average, 3D mammography is slightly better at detecting cancer, but it is not clear how much that benefits the average woman.

It is important to remember that experts now agree that most women under 50 or over 75 do not need to undergo screening mammography and that the average woman only needs to undergo screening mammography every two years instead of annually. See our article When should women start regular mammograms? 40? 50? And how often is “regular”? for more information.

Footnotes:

  1. National Cancer Institute. “SEER Stat Fact Sheets: Breast Cancer.” http://seer.cancer.gov/statfacts/html/breast.html (Accessed October 12, 2015).
  2. S. Food and Drug Administration. “Radiation-Emitting Products.” http://www.fda.gov/Radiation-EmittingProducts/MammographyQualityStandardsActandProgram/FacilityScorecard/ucm113858.htm (Accessed October 12, 2015).
  3. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic Performance of Digital versus Film Mammography for Breast-Cancer Screening. New England Journal of Medicine, 2005; 353(17): 1773-1783.
  4. Rosselli del Turco M, Mantellini P, Ciatto S, Bonardi R, Martinelli F, Lazzari B, Houssami N. Full-field digital versus screen-film mammography: Comparative accuracy in concurrent screening cohorts. American Journal of Roentgenology 2007; 189(4): 860-866. doi: 10.2214/AJR.07.2303.
  5. Kerlikowske K, Hubbard RA, Miglioretti DL, Geller BM, Yankaskas BC, Lehman CD, Taplin SH, & Sickles EA. Comparative effectiveness of digital versus film-screen mammography in community practice in the United States. Annals of Internal Medicine 2011; 155: 493-502.
  6. Sharpe RE Jr, Venkataraman S, Phillips J, Dialani V, Fein-Zachary VJ, Prakash S, Slanetz PJ, Mehta TS. Increased Cancer Detection Rate and Variations in the Recall Rate Resulting from Implementation of 3D Digital Breast Tomosynthesis into a Population-based Screening Program. Radiology. 2015 Oct 9:142036
  7. Greenberg JS, Javitt MC, Katzen J, Michael S, Holland AE. Clinical performance metrics of 3D digital breast tomosynthesis compared with 2D digital mammography for breast cancer screening in community practice. AJR Am J Roentgenol 2014;203(3):687–693.
  8. Friedewald SM, Rafferty EA, Rose SL, et al. Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA 2014;311(24):2499–2507.
  9. Lei J, Yang P, Zhang L, Wang Y, Yang K. Diagnostic accuracy of digital breast tomosynthesis versus digital mammography for benign and malignant lesions in breasts: a meta-analysis. Eur Radiol 2014;24(3):595–602.
  10. S. Food and Drug Administration. “Summary of Safety and Effectiveness Data (SSED): Selenia Dimensions 3D System.” http://www.accessdata.fda.gov/cdrh_docs/pdf8/P080003S001b.pdf (Accessed November 20, 2013).
  11. Rose S, Tidwell AL, Bujnoch LJ, Kushwaha AC, Nordmann AS, & Sexton R. Implementation of breast tomosynthesis in a routine screening practice: An observational study. AJR online; March 22, 2013. doi: 10.2214/AJR.12.9672.
  12. Skaane P, Bandos AI, Gullien R, Eben EB, Ekseth U, Haakenaasen U, Izadi M, Jebsen IN, Jahr G, Krager M, Niklason LT, Hofvind S, & Gur D. Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Radiology 2013; 267(1): 47-56. doi: 10.1148/radiol.12121373.
  13. McDonald ES, Oustimov A, Weinstein SP, Synnestvedt MB, Schnall M, Conant EF. Effectiveness of Digital Breast Tomosynthesis Compared With Digital MammographyOutcomes Analysis From 3 Years of Breast Cancer Screening. JAMA Oncol. 2016;2(6):737–743. doi:10.1001/jamaoncol.2015.5536
  14. mandates 3-D mammogram coverage. Philadelphia Inquirer. Marie McCullough October 6, 2015 http://www.philly.com/philly/health/20151006_Pa__mandates_3-D_mammogram_coverage.html
  15. Esserman LJ, Thompson IM, & Reid B. Overdiagnosis and overtreatment in cancer: An opportunity for improvement. Journal of the American Medical Association 2013: online version, E1-E2. doi:10.1001/jama.2013.108415.
  16. McDonald, E., Oustimov, A., Weinstein, S., et al. (2016). Effectiveness of Digital Breast Tomosynthesis Compared With Digital Mammography. Journal of the American Medical Association. Accessed from https://jamanetwork.com/journals/jamaoncology/fullarticle/2491465 on June 5, 2018.
  17. Neal, C. and Philpotts, L. (2017). Breast Imaging (Multimodality Screening and Breast Density). Accessed from http://archive.rsna.org/2017/17039959.pdf
  18. Kalager M, Zelen M, Langmark F, Adami H-O. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med. 2010;363(13):1203–1210.
  19. Kaunitz, A. (2010). Just How Much Does Screening Mammography Reduce Mortality From Breast Cancer. OBG Manag. Accessed from https://www.mdedge.com/obgmanagement/article/64117/gynecologic-cancer/just-how-much-does-screening-mammography-reduce.
  20. Philpotts, L. (2017). Screening for Breast Cancer Breast Imaging. Accessed from http://ctcancerpartnership.org/wp-content/uploads/2017/09/Beast-Cancer-Liane-Philpotts.pdf.

 

 

Hormonal Therapy for Pre-menopausal Women with Early Stage Breast Cancer

Anna Mazzucco, PhD, Brandel France de Bravo, MPH, Caroline Halsted, Danielle Shapiro, MD, MPH, and Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund

Breast cancer is the most common type of cancer in women around the world, and the second leading cause of cancer deaths among U.S. women. The survival rate for early-stage breast cancer is very high.  For women whose breast cancer is diagnosed before it has spread, the 5-year survival rate is 99%.  For women whose breast cancer has spread to the lymph nodes, the 5-year survival rate is 85%.

Women who are diagnosed with early-stage breast cancer almost always undergo surgery to remove the cancer (either lumpectomy/partial mastectomy or mastectomy). Most will also choose at least one other treatment in addition to surgery:

1) If they have a lumpectomy, they often undergo radiation either to shrink the tumor before surgery or to kill any cancer cells in the breast that were missed during surgery.

2) If their cancer is estrogen receptor positive (about 84% of breast cancers), many women will try to take hormonal therapy for at least five years after surgery to lower the chance of cancer in either breast in the future. For pre-menopausal women, the standard treatment is tamoxifen.[1]

Types of Hormonal Therapies for Early Stage Breast Cancer

Hormonal therapy (also called endocrine therapy or anti-estrogen therapy) is the opposite of the type of hormones women sometimes take to reduce the symptoms of menopause. It lowers your estrogen levels instead of increasing them.[1]

Hormonal therapy is recommended for most women with breast cancer, and sometimes it is taken by women who have not been diagnosed with breast cancer but are at high risk for it based on their genes or family history. When hormonal therapy is used before breast cancer develops, it is called “primary prevention” or “chemoprevention.” Chemoprevention is completely different from the drugs used in chemotherapy to treat breast cancer.[1] See our article on breast cancer prevention.

How Does Hormonal Therapy Work?

Tamoxifen is a selective estrogen receptor modulator (SERM), which means it blocks estrogen in breast tissue, but promotes it in other tissues (such as in bone and the inner lining of the uterus). Tamoxifen is only effective in breast cancers that are estrogen receptor positive.[3,4]

How Effective Are the Treatments?

The effectiveness of treatments is often reported in terms of risk or risk reduction. Risk is another word for chance–what is the chance that something will happen, such as cancer returning or the patient dying? Risk can be reported in terms of relative risk or absolute risk. Let’s use simple numbers to show what we mean: In a study, 100 women are given a new drug and 100 other women are given an older drug.  What if the study showed that 4 patients (4%) taking the older drug became nauseous compared to only 2 patients (2%) taking the new drug.  The relative risk of patients getting nauseous is 50% lower for patients taking the new drug, and that sounds impressive. But the absolute difference is only 2% — when you subtract 2% taking the new drug compared to 4% taking the old drug.

Based on the statistics, the odds may favor taking the new drug. But if the new drug costs much more or has other side effects, a patient might decide she is willing to take the 2% greater risk of becoming nauseous. We prefer to focus on the absolute difference in risk as it is more informative for patients than the relative risk.

Tamoxifen therapy after surgery for early-stage breast cancer reduces the chances of breast cancer returning and the chances of dying from breast cancer.  But it is important to consider exactly what the benefits are likely to be for you.

Benefits of 5-Year Therapy

Does tamoxifen prevent breast cancer recurrence?

A landmark report showed that about 26% of women taking tamoxifen for 5 years after their cancer was removed had a breast cancer recurrence within 10 years, compared to about 40% of women not taking tamoxifen.[6] In that study, women with early-stage breast cancer includes women with Stage 1, Stage 2, and Stage 3A; in other words, it ranges from a very tiny breast cancer to a large cancer that has spread to several lymph nodes.  The researchers defined breast cancer recurrence as the first appearance of any breast cancer including, cancer in the same breast, cancer in the opposite breast, or distant spread of cancer. However, women who took tamoxifen for 5 years had a 0.6% chance per year of having their breast cancer return in the same breast (this is called local recurrence) compared to a 1.1% chance per year in women who did not take tamoxifen.

Does tamoxifen prevent breast cancer deaths in women with breast cancer recurrence?

Most  women who had a recurrence did not die of breast cancer:  About 17% of women younger than 45 years and 22% of women aged 45-54 years who took tamoxifen died from breast cancer within 10 years of the initial diagnosis, compared to, respectively,  20% and 28% of women those same ages who did not take tamoxifen.[6]

Does tamoxifen save lives?

The benefits of tamoxifen vary depending on  certain characteristics of early-stage breast cancers, including size of the tumor, types of cancer cells, and how many lymph nodes the cancer had spread to prior to surgery.  These issues can help doctors predict the chances of breast cancer recurrence.  Therefore, it is important for you to talk with your doctor about these specific issues and which treatment options may be right for you.  Remember that some benefits (such as survival) might be more important to you than others (such as recurrence) – or not!

Preventing Breast Cancer in the Opposite Breast

About 1 in 20 (5%) women diagnosed with breast cancer will develop breast cancer in the opposite breast within the 10 years after first breast cancer diagnosis. A 2017 study in the prestigious medical journal JAMA found that taking tamoxifen can reduce the percentage of those women from developing cancer in the opposite breast within 10 years, from about 5% to  2%.[7] Unfortunately, the study authors did not report on breast cancer deaths or deaths for any other reason. Therefore, we do not know whether tamoxifen’s reduction of cancer in the opposite breast had any impact on the women’s longevity.

Benefits of Extending Therapy

One popular option is to change from tamoxifen to an aromatase inhibitor when menopause is reached (menopause occurs when a woman has not had a menstrual period for a continuous 12 months).  Read more about aromatase inhibitors in our article on post-menopausal early stage breast cancer.

Extending tamoxifen for an additional 5 years can also decrease a woman’s chances of breast cancer recurrence by about 4% in the 10 years after surgery if her cancer had spread to her lymph nodes prior to surgery.[2]  However, women who had early-stage breast cancer that did not spread to their lymph nodes did not benefit from more than 5 years of tamoxifen.[2]

In addition to reducing recurrence, the studies also found that taking tamoxifen for 10 years instead of 5 years reduced the chances of dying from breast cancer within those 10 years from about 15% to about 12%. These differences are small and disappear for women with the earliest stage breast cancers. Even more important, overall survival –how long a woman lives after her initial diagnosis of breast cancer–was not significantly affected by taking tamoxifen for more than 5 years.[2]  In other words, even if a woman taking tamoxifen for 10 years was less likely to die of breast cancer within those 10 years, she was not less likely to die from any cause.

When considering your treatment options, talk with your doctor about your overall health and your heart health, because all women (including women with breast cancer) are more likely to die from heart disease than breast cancer. And some treatments for breast cancer can harm your heart.  Read more about heart health and breast cancer in our article.

Side Effects and Risks of Treatment

Tamoxifen increases the chances of developing endometrial cancer and blood clots in the legs and lungs.[3,16] In a Danish study, the 5-year risk of developing blood clots was about 1.2% in breast cancer patients taking tamoxifen compared to 0.5% in breast cancer patients who were not taking tamoxifen.[10]  Tamoxifen often causes side effects similar to those experienced in menopause, including hot flashes and irregular periods.[16] In one study, 41% of women taking tamoxifen experienced hot flashes, and 10% experienced abnormal periods .[19]

The Bottom Line

There are many ways to treat early-stage breast cancer in pre-menopausal women, in addition to surgery. A woman’s age, tumor characteristics, and personal wishes/goals may affect the benefits and risks of different treatments. Talk with your doctor about which treatment options may be right for you by asking about the exact benefits of specific treatments on recurrence and overall survival, and considering these specific issues and not just what is best for cancer patients on average.

Footnotes:

  1. American Cancer Society. Cancer Treatment and Survivorship: Facts and Figures 2016-2017. Available online: https://www.cancer.org
  2. Burstein HJ. et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. Journal of Clinical Oncology. 2017;34(14): 1689-1701. Doi: 1200/JCO.2015.65.9573
  3. National Cancer Institute. Breast Cancer Treatment (PDQ). (Nov. 2017). Available online: https://www.cancer.gov/types/breast/patient/breast-treatment-pdq#section/_125
  4. Adjuvant Therapy for Breast Cancer. (Aug. 2017). Available online: https://emedicine.medscape.com/article/1946040-overview#showall
  5. Colleoni M. et al. Annual Hazard Rates of Recurrence for Breast Cancer During 24 Years of Follow-Up: Results From the International Breast Cancer Study Group Trials I to V. J Clin Oncol. 2016;34(9): 927-935. doi: 1200/JCO.2015.62.3504
  6. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011;378(9793): 771-784. doi:1016/S0140-6736(11)60993-8
  7. Gierach GL, Curtis RE, Pfeiffer RM, et al. Association of Adjuvant Tamoxifen and Aromatase Inhibitor Therapy With Contralateral Breast Cancer Risk Among US Women With Breast Cancer in a General Community Setting. JAMA Oncol. 2017;3(2): 186–193. doi:1001/jamaoncol.2016.3340
  8. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001): 1341 – 1352. doi: http://dx.doi.org/10.1016/S0140-6736(15)61074-1
  9. Pohlmann PR and Isaacs C. Extended Adjuvant Endocrine Therapy for Postmenopausal Women: Treating Many to Benefit a Few, JNCI: Journal of the National Cancer Institute. 2018;110(1): djx142, doi: https://doi.org/10.1093/jnci/djx142
  10. Burstein HJ, Prestrud AA, Seidenfeld J, et al. American Society of Clinical Oncology Clinical Practice Guideline: Update on Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer. Journal of Clinical Oncology. 2010;28(23):3784-3796. doi:10.1200/JCO.2009.26.3756.
  11. Blok EJ, et al. Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05). JNCI: Journal of the National Cancer Institute. 2018; 110(1): djx134, https://doi.org/10.1093/jnci/djx134
  12. Van de Velde, C.J.H. et al. Optimal duration of extended letrozole treatment after 5 years of adjuvant endocrine therapy; results of the randomized phase III IDEAL trial (BOOG 2006–05). European Journal of Cancer. 2017;72(Supp1):S9. doi: http://dx.doi.org/10.1016/S0959-8049(17)30108-9
  13. Gianni L. et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncology. 2011;12(3): 236-44. doi: https://doi.org/10.1016/S1470-2045(11)70033-X
  14. Cameron D. et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389(10075): 1195-1205. doi: https://doi.org/10.1016/S0140-6736(16)32616-2
  15. Stenger M. ASCO Post: 11-Year Follow-up of Adjuvant Trastuzumab in the HERA Trial. (March 2017). Available online: http://www.ascopost.com/News/48405
  16. Gogas H, Markopoulos C, Blamey R. Should women be advised to take prophylactic endocrine treatment outside of a clinical trial setting? Ann Oncol. 2005;16:1861-1866. Available online: https://watermark.silverchair.com
  17. Fisher B, et al. J Natl Cancer Inst. 1994; 86:527-537.
  18. Bonneterre, et al. J Clin Oncol. 2000; 18:3748-3757.
  19. Howell A, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet. 2005;365(9453): 60-2. doi: 1016/S0140-6736(04)17666-6
  20. Bliss JM. et al. Disease-Related Outcomes With Long-Term Follow-Up: An Updated Analysis of the Intergroup Exemestane Study. Journal of Clinical Oncology. 2012;30(7): 709-717. doi: 1200/JCO.2010.33.7899
  21. Drugs and Diseases: Gosarelin. Available online: https://reference.medscape.com/drug/zoladex-la-goserelin-342129
  22. Drugs and Diseases: Trastuzumab. Available online: https://reference.medscape.com/drug/herceptin-ogivri-trastuzumab-342231#5

 

Immunotherapy for Treatment of Advanced Non-Small Cell Lung Cancer

Danielle Shapiro, MD, MPH, Cancer Prevention and Treatment Fund

Immunotherapy could become the new standard of care for initial treatment of advanced lung cancer. Unfortunately, most lung cancer patients have advanced lung cancer when they are diagnosed, meaning the cancer has already spread to other areas of the body, including the brain and liver. Groundbreaking research shows that when added to chemotherapy, immunotherapy could help patients with advanced lung cancers live longer. Cancer experts presented this new research at the 2018 annual American Association for Cancer Research meeting.

This research gives hope, but it is still in the early stages of understanding what treatments work for which patients. As with a lot of new cancer drugs, we don’t yet know how these treatments may affect patients’ quality of life, and whether or not those who live for a longer period of time also have a better quality of life.

When deciding which treatments are best for you or your family member, consider the benefits of these treatments along with their side effects and costs, and not just what is best for advanced lung cancer patients on average.

What is Immunotherapy?

Immunotherapy boosts the body’s ability to kill cancer cells. It also helps the body repair damage caused by chemotherapy treatments, which are often very toxic. A certain class of immunotherapies, called “immune checkpoint inhibitors,” block the protein PDL-1. Cancer cells that make the PDL-1 are able to escape the body’s defenses, which increases the cancer’s ability to grow and spread.

Many of these immunotherapies have been approved as a second or third options to treat advanced lung cancers, only after other treatments have not worked. The results of key clinical studies described below may convince doctors to try these treatments earlier on.

Findings from Clinical Trials

Keytruda (Pembrolizumab)

More than 600 patients with advanced non-squamous, non-small cell lung cancer were studied in the Keynote-189 clinical trial.1 Their cancers did not contain certain gene mutations. About two-thirds of the patients were treated with chemotherapy plus immunotherapy and about one-third were treated with chemotherapy alone. After one year, about 69% of patients treated with immunotherapy plus chemotherapy were alive compared to about 49% of patients treated with chemotherapy alone. On average, patients who were treated with standard chemotherapy lived about 11.3 months. We don’t yet know what the average was for patients who received immunotherapy plus chemotherapy.

Immunotherapy also delayed progression of cancers (also known as “progression free survival”). That is, compared to standard chemotherapy, patients treated with immunotherapy lived for a longer period of time where their cancer either stayed the same or decreased in size. At one year, about 34% of patients who received immunotherapy were alive without progression compared to about 17% of patients treated with chemotherapy alone. On average, patients who received immunotherapy lived about 9 months without progression compared to about 5 months in patients treated with chemotherapy alone.

Nivolumab (Opdivo) plus Ipilimumab (Yervoy)

Almost 2,000 patients with advanced squamous and non-squamous, non-small cell lung cancer were studied in the CheckMate 227 trial.2 Their cancers did not contain certain gene mutations. The researchers used a new experimental grouping system called “tumor mutational burden,” or TMB. Studies show that cancers with a higher TMB are more likely to respond to immunotherapy.

In patients with a high TMB, at one year, about 43% of patients treated with combination immunotherapy plus chemotherapy were alive without progression compared to about 13% of patients treated with chemotherapy alone.

On average, patients with a high TMB who received combination immunotherapy lived about 7.2 months without progression compared to about 5.5 months in patients treated with chemotherapy alone.

However, research does not yet tell us if the patients taking these drugs lived longer. “Overall survival” measures how long a patient lives regardless of whether he/she dies from lung cancer or something else. That’s especially important with cancer treatment, because the treatment itself can be so toxic that it kills some patients. Since the difference in progression-free survival is less than 2 months, there may be no difference in terms of living longer. An added question is whether side effects from the drug are so unpleasant that the patients are not really benefiting.

Atezolizumab (Tecentriq) plus Bevacizumab (Avastin)

About 1,200 patients with advanced non-squamous, non-small cell lung cancer were studied in the IMpower 150 trial.3 The majority of cancers did not contain certain gene mutations, but some did. IMpower 150 studied the benefit of immunotherapy plus bevacizumab. Bevacizumab (Avastin) is a “VEGF inhibitor,” which means it blocks cancer cells from making new blood vessels. Bevacizumab plus chemotherapy is approved by the U.S. FDA for treating advanced non-squamous, non-small cell lung cancer.

At one year, about 37% of patients treated with combination bevacizumab and immunotherapy plus chemotherapy were alive without progression compared to about 18% of patients treated with bevacizumab plus chemotherapy.

On average, patients who received combination immunotherapy and bevacizumab plus chemotherapy lived about 8.3 months without progression compared to about 6.8 months in patients treated with bevacizumab plus chemotherapy. Surprisingly, patients whose lung cancer had certain gene mutations had a similar benefit. Previously, scientists believed that immunotherapy provided no benefit for patients whose lung cancers carried certain gene mutations.

However, research does not yet tell us if the patients taking these drugs lived longer. Since the difference in progression-free survival is only 1.5 months, there may be no difference in terms of living longer. An added question is whether side effects from the drug are so unpleasant that the patients are not really benefiting.

Treatment Side Effects

On average, side effects of immunotherapy were similar to chemotherapy alone. Common side effects include nausea, vomiting, diarrhea, and rash. Serious side effects include a weakened immune system and inflammation of the lungs, liver and the kidneys. In a few cases, patients with inflammation of the lungs died.

The Bottom Line

Immunotherapy has been used for advanced lung cancer when other options have not worked. This new research shows that some of these therapies may be beneficial if used sooner after diagnosis. When deciding which treatments are best for you or your family member, consider the benefits of these treatments along with their side effects and costs, and not just what is best for advanced lung cancer patients on average. Ask the tough questions about evidence of living longer (not just whether you would die of lung cancer) and about quality of life when you talk with your doctor about which treatment options may be right for you.

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

References:

Gandhi, Leena et al. Pembrolizumb plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1801005

Hellmann, Matthew D. et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1801946

First Line Combination Therapy Improves Progression-Free Survival in Advanced Lung Cancer. European Society for Medical Oncology. 2017. http://www.esmo.org/Latest-News/First-Line-Combination-Therapy-Improves-Progression-Free-Survival-In-Advanced-Lung-Cancer