Category Archives: Medical Treatments with Cancer Risks

Compounded Bioidentical Hormone Therapy

Keris KrennHrubec, Meg Seymour, & Diana Zuckerman, PhD


To avoid the risks of conventional hormone therapy, more and more women are seeking alternatives. But how safe are compounded bioidentical hormones?

When women enter menopause, their bodies produce less estrogen and progesterone. This can cause hot flashes, night sweats, insomnia and other symptoms. Hormone therapy can supplement those hormones, but it increases the risk of breast cancer and other serious diseases. What are your options if the symptoms of menopause are difficult to cope with?

In 2002, a major research study reported that FDA-approved hormone therapy can increase a woman’s risk of heart disease, breast cancer, and stroke. (For more information, please visit: Hormone Therapy and Menopause). As a result, women started to look for alternatives to conventional hormone therapy. Custom-compounded bioidentical hormone therapy (CBHT) has been marketed as more natural and safer, but does the scientific evidence support those claims?

Natural and Safe?

Many of the hormones used in conventional hormone therapy are derived from animal products. Bioidentical hormones, on the other hand, are from plants and are more similar (although not necessarily identical) to the hormones that naturally occur in the human body. However, the term “bioidentical” is misleading and has no scientific value. Bioidenticals are created in laboratories through at least 15 chemical reactions, and they are not identical to hormones produced by human bodies.[1,2] To date, no studies have shown that bioidenticals are safer than conventional hormone therapy and experts used to assume they have similar benefits and risks for patients.[3,4]

The FDA asked the National Academies of Sciences, Engineering and Medicine to form a committee that would assess whether cBHT is an adequate substitute for the traditional therapies that are FDA-approved. In 2020, the committee issued a report that there was not sufficient data to say that cBHT is a safe and effective treatment for menopause. Although some people have reported anecdotal claims that cBHT is safe and effective, these anecdotes are not scientific data.[5] 

The Pros and Cons of Compounding

Some bioidentical hormones (such as small particles of progesterone and estradiol) have been approved by the FDA,[1] but most are not. Instead, they are prescribed as a compound with ingredients that are mixed and blended by pharmacies to “create a customized medication for an individual patient”.[6,7] Since compounding is used to make individualized medication, it is not approved by the FDA. Compounding of some medications is necessary for some patients, such as patients who are allergic to one component of an approved drug or who need a particular dosage that differs from the FDA-approved medicine. However, since it is not monitored the way an FDA-approved drug is, compounded drugs are not proven to be safe or effective.[7]

Women who are considering compounded bioidentical hormones often start by getting their individual hormone levels checked through saliva or serum tests. This may create the impression that the bioidentical drugs will be customized for each patient, but research has not shown that these hormonal tests are meaningful or can ensure a safe or effective product.[1,3]

Risks Through Compounding

In addition to not being approved by the FDA as safe or effective, compounded drugs have an additional risk of being contaminated [3] or having an inaccurate dosage.[6] Either can be dangerous. Since compounded drugs are not FDA-approved, they also lack warnings on labels about possible side effects, including serious ones.[1,8] Several of the ingredients that are commonly used in bioidentical hormones – such as testosterone – have not been approved by the FDA for use for postmenopausal women.[3]

Despite these concerns, many women have been prescribed bioidentical hormones for menopause. That’s why the FDA announced in 2018 that they will expand research on compounded bioidentical hormone therapy.[9]

How Do I Know If My Hormone Therapy Has Been Compounded?

Compounded bioidentical drugs are legal if they are in response to a doctor’s prescription.[7] It is unlawful for a pharmacy to simply give you modified drugs without consent. However, even if it is legal, that doesn’t mean it will be safe or effective. If you have any questions or concerns about your hormone therapy, you should talk to your doctor or pharmacist.[10]

You can recognize FDA-approved hormone therapy by the use of brand names such as Premarin, Vagifem and Estrace. The bioidenticals micronized progesterone (brand name Prometrium) and estradiol (brand name Vivelle) have also been approved by the FDA. If your medication has been compounded, you will see terms such as estrone, estradiol, testosterone or progesterone instead of brand names. You are probably receiving CBHT if you have been asked for a saliva or serum test to establish an individualized treatment course.[1,2]

Traditional hormone therapy can be effective for menopausal symptoms, but can increase the risk of cancer and other serious diseases. Bioidentical hormones may have the same risks. You can find more information on the FDA-approved hormone therapies here.

 

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

  1. American College of Obstetricians. (2012). Compounded bioidentical menopausal hormone therapy. Fertility and Sterility, 98(2), 308-312. (reaffirmed in 2018)
  2. Gass, M. L., Stuenkel, C. A., Utian, W. H., LaCroix, A., Liu, J. H., & Shifren, J. L. (2015). Use of compounded hormone therapy in the United States: report of the North American Menopause Society Survey. Menopause, 22(12), 1276-1285.
  3. Pinkerton, J. V., & Pickar, J. H. (2016). Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy. Menopause (New York, NY), 23(2), 215.
  4. National Institute on Aging. (June 2017). Hot Flashes: What Can I Do? Retrieved from: https://www.nia.nih.gov/health/hot-flashes-what-can-i-do#risks
  5. The National Academies of Sciences, Engineering and Medicine (July 2020). Report: The Clinical Utility of Compounded Bioidentical Hormone Therapy (cBHT) A Review of Safety, Effectiveness, and Use. Retrieved from: https://www.nap.edu/resource/25791/cBHT%20Consensus%20Study%20Report%20Highlights.pdf
  6. FDA (June 2018). Report: Limited FDA Survey of Compounded Drug Products. Retrieved from: https://www.fda.gov/drugs/human-drug-compounding/report-limited-fda-survey-compounded-drug-products
  7. FDA (June 2018). Compounding and the FDA: Questions and Answers. Retrieved from: https://www.fda.gov/drugs/human-drug-compounding/compounding-and-fda-questions-and-answers.
  8. FDA (June 2018). Compounding Oversight. Retrieved from: https://www.fda.gov/drugs/human-drug-compounding/compounding-oversight
  9. FDA (September 2018). FDA announces new and expanded compounding research projects. Retrieved from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-new-and-expanded-compounding-research-projects
  10. FDA (February 2018). Menopause: Medicines to Help You. Retrieved from: https://www.fda.gov/consumers/free-publications-women/menopause-medicines-help-you

Allergan Recalls Textured Breast Implants Globally Due to Cancer Links

Sasha Chavkin, IJIC: July 24, 2019.


Allergan will recall its Biocell textured breast implants worldwide after United States health authorities requested that it remove them from the market due to their association with a rare cancer of the immune system.

The announcement, which reflects the most sweeping recognition to date of the serious health risks associated with breast implants, comes after the U.S. Food and Drug Administration obtained new data showing that Allergan implants were linked to most known cases of the cancer, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

“Once the evidence indicated that a specific manufacturer’s product appeared to be directly linked to significant patient harm, including death, the FDA took action to alert the firm to new evidence indicating a recall is warranted to protect women’s health,” said FDA Principal Deputy Commissioner Amy Abernethy, in a statement issued by the agency.

The company said the recalled implants, both saline and silicone, would no longer be distributed or sold in any market where they are currently available.

[…]

President of the National Center for Health Research Diana Zuckerman, who has called for stricter oversight of breast implants, said Allergan’s recall was a step in the right direction but did not eliminate the risks of BIA-ALCL.

“When women decide to get breast implants for reconstruction after mastectomy or for breast augmentation, they should not be putting their lives at risk for lymphoma,” Zuckerman said.

“This recall will reduce that risk but it won’t eliminate it, because the FDA has stated that not all women with BIA-ALCL had these specific types of implants.”

In its press conference, the FDA said that it was considering additional measures to protect patient safety.

The agency said it would soon announce updated labeling standards for breast implants, and that these might include a black box safety warning, which is reserved for products that pose the most serious health risks.

The FDA also said it might require a patient checklist, a document that briefly states the key health risks from breast implants which patients would sign before undergoing surgery. The agency is not recommending that women who currently have Allergan Biocell implants get their implants removed, unless they experience signs or symptoms of BIA-ALCL.

Read the full story here.

Allergan Recalls Textured Breast Implants Linked to Rare Cancer

Laurie McGinley, Washington Post: July 24, 2019.


Allergan announced a worldwide recall of textured breast implants Wednesday after the Food and Drug Administration found a sharp increase in a rare cancer and deaths linked to the products and asked the company to pull them off the U.S. market.

The Dublin-based company said it is recalling Biocell textured breast implants and tissue expanders from all markets in which they are sold. The devices had already been banned or recalled in several countries.

The FDA said the new data shows that 573 cases worldwide have linked the rare cancer to the implants since the agency began tracking the issue in 2011. The vast majority of those cases involve Allergan products. Thirty-three women have died of what’s known as breast implant-associated anaplastic large cell lymphoma, a cancer of the immune system. Of those fatalities, authorities identified the implant manufacturer in 13 cases — and it was Allergan in all but one.

In February, the last time the FDA had updated its numbers on implant-associated illness, it reported 457 cases and nine deaths worldwide.

The agency said Wednesday that the latest data indicates the risk of such disease is six times greater with Allergan Biocell textured implants than with other types of textured implants sold in the United States.

The FDA’s new stance against the Biocell product is a reversal of its posture a few months ago, when it said there was insufficient evidence to try to remove the devices from the market.

Jeffrey Shuren, director of the FDA’s Center for Devices and Radiological Health, said on a news call the agency changed its position partly after seeing the sharp increase in reported deaths.

Allergan pulled the products off the European market last year. Canada banned them in May after finding an increased risk of cancer.

[…]

Diana Zuckerman, president of the National Center for Health Research, a nonprofit organization, welcomed the FDA’s decision to press Allergan to recall the implants. “We are very glad they have done it,” she said. “I think they could have done it months ago and I hope a lot of women have not been getting these implants in the meantime.”

The FDA said that in most cases, the rare lymphoma linked to the implants is found in scar tissue and fluid near the devices, but that sometimes it can spread throughout the body. The condition can be life-threatening if it isn’t diagnosed and treated promptly, the agency said. Most patients are treated successfully by surgery to remove the implant and scar tissue but some may require chemotherapy or radiation.

Scientists are not sure why certain textured implants might be linked to the rare cancer. “We don’t know what it is that might increase the risk,” said Binita Ashar, director of the FDA’s office of surgical and infection control devices.

The agency said its data on the rising incidence of illnesses and deaths related to the implants came from medical device reports and searches of medical literature.

See the full article here.

Allergan Recalls Textured Breast Implant Tied to Rare Cancer

Matthew Perrone, AP for ABC Action News; July 24, 2019


WASHINGTON (AP) — Breast implant maker Allergan Inc. issued a worldwide recall Wednesday for textured models because of a link to a rare form of cancer.

The U.S. Food and Drug Administration said it called for the removal after new information showed Allergan’s Biocell breast implants with a textured surface account for a disproportionate share of rare lymphoma cases. The move follows similar action in France, Australia and Canada.

The FDA is not recommending women with the implants have them removed if they are not experiencing problems.

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 Photo by: Matt McGlashen 

WASHINGTON (AP) — Breast implant maker Allergan Inc. issued a worldwide recall Wednesday for textured models because of a link to a rare form of cancer.

The U.S. Food and Drug Administration said it called for the removal after new information showed Allergan’s Biocell breast implants with a textured surface account for a disproportionate share of rare lymphoma cases. The move follows similar action in France, Australia and Canada.

The FDA is not recommending women with the implants have them removed if they are not experiencing problems.

[…]

The FDA said the latest figures show more than 80 percent of the 570 confirmed cases of the lymphoma worldwide have been linked to Allergan implants. The updated figures reflect 116 new cases of the cancer since the FDA last released figures earlier this year.

The new numbers still reflect a rare disease considering an estimated 10 million women globally have breast implants.

There is no firm agreement on the exact frequency of the disease, known as breast implant-associated anaplastic large cell lymphoma. Published estimates ranging from 1 in 3,000 patients to 1 in 30,000 patients.

Diana Zuckerman, a researcher who has studied breast implant safety, called the removal of the devices inevitable.

“Either the company would voluntarily decide to withdraw them from the market to protect from lawsuits, or the FDA would persuade Allergan to do so,” Zuckerman said in an email.

Read the full story here.

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

Hormone Therapy and Menopause

Anna E. Mazzucco, PhD, Elizabeth Santoro, RN, MPH, Maushami DeSoto, PhD, and Jae Hong Lee, MD, MPH

 Do women need to “replace” hormones as they age? Millions of women struggle with the decision about hormones during and after menopause: should I go on, should I stay on, or should I go off?

For decades, women were told that hormone therapy was like a fountain of youth that would protect them against many of the diseases and symptoms of aging that increase after menopause. Since estrogen alone was known to increase the risk of uterine cancer, doctors usually prescribed a combination of estrogen and progestin, unless a woman had a hysterectomy and therefore was at no risk of uterine cancer.

In addition to its proven effectiveness for decreasing hot flashes, night sweats, and vaginal dryness, in the 1980’s and 1990’s hormone therapy was thought to decrease osteoporosis, prevent heart disease, improve memory and concentration, reduce wrinkles, and improve mood. Women were encouraged to start hormone therapy before menopause started and to continue to take it for years, if not decades, in order to improve their health and their quality of life.

However, the research evidence is now clear: the risks of hormones outweigh the benefits for the vast majority of women.

What the Research Says

In December 2017, the experts at the U.S. Preventive Services Task Force issued a clear recommendation:  post-menopausal women should NOT take hormones to prevent chronic health conditions, such as increasing bone strength to avoid fractures. The reason is that the risks of these hormones outweigh the benefits.

This recommendation is just the latest evidence that taking hormones to “replace” those that are reduced in menopause if often bad for your health. Previous evidence came from the Women’s Health Initiative (WHI), sponsored by the National Institutes of Health (NIH), which included more than 27,000 women in three different trials to study the effect of hormones on women’s bodies. The 3 trials were: 1) the Estrogen Plus Progestin Trial, 2) the Women’s Health Initiative Memory Study, and 3) the Estrogen-alone Trial.

The researchers found that women taking a combination of estrogen and progesterone hormones were more likely to develop breast cancer, stroke, and blood clots, and at least as likely to develop heart disease, compared to women taking placebo. Those on estrogen alone were at an increased risk for strokes and at a significantly increased risk for deep vein, thrombosis.† The memory Study revealed that women taking a combination of estrogen plus progesterone were twice as likely to develop Alzheimer’s Disease and other forms of dementia compared to women on placebo.

All the three trials were stopped early for ethical reasons when it became clear that women taking hormones were more likely to be harmed than helped. While there are some short-term benefits to taking hormones, the researchers concluded that for most women, the risks of hormone therapy outweigh the benefits.

Following release of these findings, use of hormone therapy in the U.S. dropped significantly.  Since then, several large studies have pointed out that breast cancer incidence also dropped a few years after the decline inHRT use.1,,2  This unexpected and unprecedented drop in breast cancer incidence suggests that HRT has a more dramatic impact on breast cancer risk than previously thought.3

In 2009, a study found that hormone therapy increased the risk of dying of lung cancer among women who smoked or previously smoked, compared to smokers or former smokers who did not take hormone therapy. For more information click here.

In 2010 the University of California at San Francisco did a study of nearly 700,000 women. The researchers found that taking hormones may actually promote the growth of tumors in the breast which increases the incidents of invasive cancer and the risk of ductal carcinoma in situ (DCIS), a form of non-invasive pre-cancer. You can read more about that study by clicking here.

Experts who promote the use of HRT have criticized the WHI for enrolling women after menopause rather than just before or in the earliest stages.  So, it is important to note that in 2014, a study of 727 women in early menopause showed that hormone therapy did not prevent atherosclerosis (artery thickening), as had been claimed previously.  Following women on HRT for 4 years, the researchers from the Kronos Longevity Research Institute, a pro-HRT research institute, and other institutions, found no difference in artery thickening between the women who took HRT and those who didn’t.4  In 2015, the same group published an article admitting that hormone therapy also had no impact on “cognitive decline,” despite claims that it would prevent Alzheimer’s and memory loss. 5  Although the authors focused on a small improvement in mood related to using hormone pills for 4 years (but not found with hormone creams), they downplayed the more important finding: no impact on depression as measured by the valid and reliable Beck Depression Inventory.

What are the Risks and Benefits of Hormone Therapy?

To emphasize that lost hormones don’t necessarily need to be replaced, the term “hormone replacement therapy” has been changed to “hormone therapy.” Experts now advise women to use hormone therapy only for severe symptoms of menopause that reduce the quality of life, such as severe hot flashes, night sweats, insomnia, and vaginal dryness. Women are urged to take hormones at the lowest dose that is effective and for the shortest possible period of time. However, even short-term use (less than one year) increases some risks; for example, the increase in heart disease comes primarily from the first year of hormone use.

Hormone therapy may be recommended in severe cases of vulvar and vaginal atrophy as well as for treating severe postmenopausal osteoporosis when non-estrogen medications or other strategies are unsuccessful or impossible. A decision to use any combination of estrogen and progestin should be discussed with a physician who is expert on the topic, and specific criteria for the indication, dose, and duration of these hormones must be met prior to their prescription and administration.

Risks:

Compared to women taking placebo, within 5 years the women who received estrogen plus progestinexperienced:
— 41% more strokes
— 29% more heart attacks
— twice as many blood clots
— 22% more heart disease of all types
— 26% more breast cancer
— 37% fewer cases of colorectal cancer
— one-third fewer hip fractures
— 24% fewer bone fractures of any type
— no difference in the overall death rate

It’s important to note that only 2.5% of the women in the study experienced health problems. So, while the percentage increase in some diseases was rather large, the risk for most patients remained relatively small. That does not mean these risks are not important however.

To provide a better sense of the additional risks that come with combination hormone therapy, the study data can be summarized more simply. Compared to a group of 10,000 women taking placebo, 10,000 women taking combination hormone therapy will experience:
— 7 more heart attacks
— 8 more strokes
— 8 more cases of breast cancer
— 18 more blood clots
— 6 fewer cases of colorectal cancer
— 5 fewer hip fractures

Research Evidence

The Women’s Health Initiative was a major 15-year research program to address the most common causes of death, disability and poor quality of life in post-menopausal women – cardiovascular disease, cancer, and osteoporosis. The WHI was launched in 1991 and consisted of a set of clinical trials and an observational study. The clinical trials were designed to test the effects of post-menopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancer.

The hormone trial had two studies: the estrogen-plus-progestin study of women with a uterus and the estrogen-alone study of women without a uterus. (Women with a uterus were given progestin in combination with estrogen, a practice known to prevent endometrial cancer.) In both hormone therapy studies, women were randomly assigned to either the hormone medication being studied or to placebo. Those studies ended several years ago, and the women are now participating in a follow-up phase, which will last until 2010.

Estrogen plus Progestin Trial (stopped in July 2002)

Compared with women in the placebo those on estrogen plus progestin had:

  • Increased risk of heart attack
  • Increased risk of stroke
  • Increased risk of blood clots
  • Increased risk of breast cancer
  • Reduced risk of colorectal cancer
  • Fewer fractures
  • No protection against mild cognitive impairment and increased risk of dementia (study included only women 65 and older)
  • Increased risk of dying of lung cancer
Women’s Health Initiative Memory Study (stopped in May 2003)
  • Women taking hormones had twice the risk for developing dementia
  • Hormones provided no protection against mild cognitive impairment/memory loss
Estrogen-alone Trial (stopped in February 2004)
  • Estrogen increased risk for stroke
  • Estrogen decreased risk for hip fracture
  • No positive or negative effect on breast cancer

Compared to placebo women on estrogen alone had:

  • Increased risk of stroke
  • Increased risk of blood clots
  • Uncertain effect for breast cancer
  • No difference in risk for colorectal cancer
  • No difference in risk for heart attack
  • Reduced risk of fracture

Links to Research Information

Estrogen Plus Progestin Trial: July 2002
The Women’s Health Initiative Memory Study: May 2003
The Estrogen-alone Trial: February 2004

_______________________________________________

† Deep vein thrombosis refers to a blood clot deep inside the veins, usually in the legs.
‡ Symptoms include thinning and inflammation of the vaginal walls and changes in the vulva.

A Shocking Diagnosis: Breast Implants “Gave Me Cancer”

Denise Grady, The New York Times: May 14, 2017

Raylene Hollrah was 33, with a young daughter, when she learned she had breast cancer. She made a difficult decision, one she hoped would save her life: She had her breasts removed, underwent grueling chemotherapy and then had reconstructive surgery.

In 2013, six years after her first diagnosis, cancer struck again — not breast cancer, but a rare malignancy of the immune system — caused by the implants used to rebuild her chest.

“My whole world came crumbling down again,” said Ms. Hollrah, now 43, who owns an insurance agency in Hermann, Mo. “I had spent the past six years going to the oncologist every three months trying to keep cancer away, and here was something I had put in my body to try to help me feel more like a woman, and it gave me cancer. I thought, ‘I’m not going to see my kids grow up.’”

Her disease — breast implant-associated anaplastic large-cell lymphoma — is a mysterious cancer that has affected a tiny proportion of the more than 10 million women worldwide who have received implants. Nearly all the cases have been linked to implants with a textured or slightly roughened surface, rather than a smooth covering. Texturing may cause inflammation that leads to cancer. If detected early, the lymphoma is often curable.

The Food and Drug Administration first reported a link between implants and the disease in 2011, and information was added to the products’ labeling. But the added warnings are deeply embedded in a dense list of complications, and no implants have been recalled. The F.D.A. advises women only “to follow their doctor’s recommended actions for monitoring their breast implants,” a spokeswoman said in an email this month.

 Until recently, many doctors had never heard of the disease, and little was known about the women who suddenly received the shocking diagnosis of cancer brought on by implants.

An F.D.A. update in March that linked nine deaths to the implants has helped raise awareness. The agency had received 359 reports of implant-associated lymphoma from around the world, although the actual tally of cases is unknown because the F.D.A.’s monitoring system relies on voluntary reports from doctors or patients. The number is expected to rise as more doctors and pathologists recognize the connection between the implants and the disease.

Women who have had the lymphoma say that the attention is long overdue, that too few women have been informed of the risk and that those with symptoms often face delays and mistakes in diagnosis, and difficulties in receiving proper care. Some have become severely ill.

Implants have become increasingly popular. From 2000 to 2016, the number of breast augmentations in the United States rose 37 percent, and reconstructions after mastectomy rose 39 percent. Annually, nearly 400,000 women in the United States get breast implants, about 300,000 for cosmetic enlargement and about 100,000 for reconstruction after cancer, according to the American Society of Plastic Surgeons. Allergan and Mentor are the major manufacturers. Worldwide, an estimated 1.4 million women got implants in 2015.

As late as 2015, only about 30 percent of plastic surgeons were routinely discussing the cancer with patients, according to Dr. Mark W. Clemens II, a plastic surgeon and an expert on the disease at the University of Texas MD Anderson Cancer Center in Houston.

“I’d like to think that since then we’ve made progress on that,” Dr. Clemens said.

Late last year, an alliance of cancer centers, the National Comprehensive Cancer Network, issued treatment guidelines. Experts agree that the essential first step is to remove the implant and the entire capsule of scar tissue around it. Otherwise, the disease is likely to recur, and the prognosis to worsen.

Not all women have been able to get the recommended treatment. Kimra Rogers, 50, a nursing assistant in Caldwell, Idaho, learned last May that she had lymphoma, from textured implants she had for more than 10 years. But instead of removing the implants and capsules immediately, her doctor prescribed six rounds of chemotherapy and 25 rounds of radiation. A year later, she still has the implants.

“Unfortunately, my doctor didn’t know the first line of defense,” Ms. Rogers said.

She learned about the importance of having the implants removed only from other women in a Facebook group for those with the disease.

Her health insurer, Blue Cross Blue Shield of Montana, covered the chemotherapy and radiation but has refused to pay for removal of the implants, and told her that her appeal rights were “exhausted.” In a statement sent to The New York Times, a spokesman said, “Cosmetic breast implants are a contract exclusion, as are any services related to complications of the cosmetic breast implants, including implant removal and reconstruction.”

Physicians dispute that reasoning, saying the surgery is needed to treat cancer. Her lawyer, Graham Newman, from Columbia, S.C., said he was planning a lawsuit against the implant makers, and had about 20 other clients with breast-implant lymphoma from Australia, Canada, England and the United States.

Ms. Rogers has been unable to work for a year. If she has to pay to have the implants removed, it will mean taking out a $12,000 loan.

“But it’s worth my life,” she said.

Insurers generally cover implants after a mastectomy, but not for cosmetic enlargement, which costs $7,500 or more. Repeat operations for complications are also common, and usually cost more than the original surgery.

Diagnosis and Treatment

Most of the cancers have developed from two to 28 years after implant surgery, with a median of eight. A vast majority occurred with textured implants.

Most implants in the United States are smooth. But for some, including those with teardrop shapes that would look odd if they rotated, texturing is preferable, because tissue can grow into the rough surface and help anchor the implant.

Researchers estimate that in Europe and the United States, one in 30,000 women with textured implants will develop the disease. But in Australia the estimate is higher: one in 10,000 to one in 1,000. No one knows why there is such a discrepancy.

What’s inside the implant — silicone or saline — seems to make no difference: Case numbers have been similar for the two types. The reason for the implants — cosmetic breast enlargement or reconstruction after a mastectomy — makes no difference, either.

Symptoms of the lymphoma usually include painful swelling and fluid buildup around the implant. Sometimes there are lumps in the breast or armpit.

To make a diagnosis, doctors drain fluid from the breast and test it for a substance called CD30, which indicates lymphoma.

The disease is usually treatable and not often fatal. Removing the implant and the entire capsule of scar tissue around it often eliminates the lymphoma. But if the cancer has spread, women need chemotherapy and sometimes radiation.

“In the cases where we have seen bad outcomes, it was usually because they were not treated or there was a major delay in treatment, on the level of years,” Dr. Clemens said. Doctors at MD Anderson have treated 38 cases and have a laboratory dedicated to studying the disease.

About 85 percent of cases can be cured with surgery alone, he said. But he added that in the past, before doctors understood how well surgery worked, many women were given chemotherapy that they probably did not need.

Case reports on the F.D.A. website vary from sketchy to somewhat detailed and rarely include long-term follow-up. Some describe initial diagnoses that were apparently mistaken, including infection and other types of cancer. In some cases, symptoms lasted or recurred for years before the right diagnosis was made.

What exactly causes the disease is not known. One theory is that bacteria may cling to textured implants and form a coating called a biofilm that stirs up the immune system and causes persistent inflammation, which may eventually lead to lymphoma. The idea is medically plausible, because other types of lymphoma stem from certain chronic infections. Professional societies for plastic surgeons recommend special techniques to avoid contamination in the operating room when implants are inserted.

“It could also just be the immune system response to some component of the texturing,” Dr. Clemens said. The rough surface may be irritating or abrasive. Allergan implants seem to be associated with more cases than other types, possibly because they are more deeply textured and have more surface area for bacteria to stick to, he said. Allergan uses a “lost-salt” method that involves rolling an implant in salt to create texture and then washing the salt away. Other makers use a sponge to imprint texturing onto the implant surface.

Allergan is studying bacterial biofilms, and immune and inflammatory responses to breast implants, a spokesman said in an email. He said the company took the disease seriously and was working with professional societies to distribute educational materials about it.

Another possible cause is that some women have a genetic trait that somehow, in the presence of implants, predisposes them to lymphoma. Dr. Clemens said researchers were genetically sequencing 50 patients to look for mutations that might contribute to the disease.

Dr. Clemens was a paid consultant for Allergan from 2013 to 2015, but not for breast implants, and no longer consults for any company, he said.

A spokeswoman for Mentor said the company was monitoring reports about the lymphoma, and stood behind the safety of its implants.

[…]

Read the full article here.

Hormone replacement therapy and breast cancer

By Elizabeth Santoro, RN, MPH, Maushami DeSoto, PhD, and Jae Hong Lee, MD, MPH

Do women need to “replace” hormones as they age? Millions of women struggle with the decision about hormones during and after menopause: should I go on, should I stay on, or should I go off?

For decades, women were told that hormone therapy was like a fountain of youth that would protect them against many of the diseases and symptoms of aging that increase after menopause. Since estrogen alone was known to increase the risk of uterine cancer, doctors usually prescribed a combination of estrogen and progestin, unless a woman had a hysterectomy and therefore was at no risk of uterine cancer.

In addition to its proven effectiveness for decreasing hot flashes, night sweats, and vaginal dryness, in the 1980’s and 1990’s hormone therapy was thought to decrease osteoporosis, prevent heart disease, improve memory and concentration, reduce wrinkles, and improve mood. Women were encouraged to start hormone therapy before menopause started and to continue to take it for years, if not decades, in order to improve their health and their quality of life.

However, the research evidence is now clear: the risks of hormones outweigh the benefits for the vast majority of women.

What the research says

Research shows that, “replacing” the hormones women lose as they age is not only unnecessary, but it can bad for your health. The Women’s Health Initiative (WHI), sponsored by the National Institutes of Health (NIH), enrolled over 27,000 women in three different trials to study the effect of hormones on women’s bodies. The 3 trials were: 1) the Estrogen Plus Progestin Trial, 2) the Women’s Health Initiative Memory Study, and 3) the Estrogen-alone Trial.

The researchers found that women taking a combination of estrogen and progesterone hormones were more likely to develop breast cancer, stroke, and blood clots, and at least as likely to develop heart disease, compared to women taking placebo. Those on estrogen alone were at an increased risk for strokes and at a significantly increased risk for deep vein, thrombosis.† The memory Study revealed that women taking a combination of estrogen plus progesterone were twice as likely to develop Alzheimer’s Disease and other forms of dementia compared to women on placebo.

All the three trials were stopped early for ethical reasons when it became clear that women taking hormones were more likely to be harmed than helped. While there are some short-term benefits to taking hormones, the researchers concluded that for most women, the risks of hormone therapy outweigh the benefits.

Following release of these findings, use of hormone therapy in the U.S. dropped significantly.  Since then, several large studies have pointed out that breast cancer incidence also dropped a few years after the decline in HRT use. 6, 7  This unexpected and unprecedented drop in breast cancer incidence suggests that HRT has a more dramatic impact on breast cancer risk than previously thought. 8  In 2009, a study found that hormone therapy increased the risk of dying of lung cancer among women who smoked or previously smoked, compared to smokers or former smokers who did not take hormone therapy. For more information click here.

In 2010 the University of California at San Francisco did a study of nearly 700,000 women. The researchers found that taking hormones may actually promote the growth of tumors in the breast which increases the incidents of invasive cancer and the risk of ductal carcinoma in situ (DCIS), a form of non-invasive pre-cancer. You can read more about that study by clicking here.

Experts who promote the use of HRT have criticized the WHI for enrolling women after menopause rather than just before or in the earliest stages.  So, it is important to note that in 2014, a study of 727 women in early menopause showed that hormone therapy did not prevent atherosclerosis (artery thickening), as had been claimed previously.  Following women on HRT for 4 years, the researchers from the Kronos Longevity Research Institute, a pro-HRT research institute, and other institutions, found no difference in artery thickening between the women who took HRT and those who didn’t. 9   In 2015, the same group published an article admitting that hormone therapy also had no impact on “cognitive decline,” despite claims that it would prevent Alzheimer’s and memory loss. 10  Although the authors focused on a small improvement in mood related to using hormone pills for 4 years (but not found with hormone creams), they downplayed the more important finding: no impact on depression as measured by the valid and reliable Beck Depression Inventory.

What are the risks and benefits of hormone therapy?

To emphasize that lost hormones don’t necessarily need to be replaced, the term “hormone replacement therapy” has been changed to “hormone therapy.” Experts now advise women to use hormone therapy only for severe symptoms of menopause that reduce the quality of life, such as severe hot flashes, night sweats, insomnia, and vaginal dryness. Women are urged to take hormones at the lowest dose that is effective and for the shortest possible period of time. However, even short-term use (less than one year) increases some risks; for example, the increase in heart disease comes primarily from the first year of hormone use.

Hormone therapy may be recommended in severe cases of vulvar and vaginal atrophy as well as for treating severe postmenopausal osteoporosis when non-estrogen medications or other strategies are unsuccessful or impossible. A decision to use any combination of estrogen and progestin should be discussed with a physician who is expert on the topic, and specific criteria for the indication, dose, and duration of these hormones must be met prior to their prescription and administration.

To learn more about the debate about hormone therapy for menopause, click here.

Risks:

Compared to women taking placebo, within 5 years the women who received estrogen plus progestin experienced:
— 41% more strokes
— 29% more heart attacks
— twice as many blood clots
— 22% more heart disease of all types
— 26% more breast cancer
— 37% fewer cases of colorectal cancer
— one-third fewer hip fractures
— 24% fewer bone fractures of any type
— no difference in the overall death rate

It’s important to note that only 2.5% of the women in the study experienced health problems. So, while the percentage increase in some diseases was rather large, the risk for most patients remained relatively small. That does not mean these risks are not important however.

To provide a better sense of the additional risks that come with combination hormone therapy, the study data can be summarized more simply. Compared to a group of 10,000 women taking placebo, 10,000 women taking combination hormone therapy will experience:
— 7 more heart attacks
— 8 more strokes
— 8 more cases of breast cancer
— 18 more blood clots
— 6 fewer cases of colorectal cancer
— 5 fewer hip fractures

Research evidence

The Women’s Health Initiative was a major 15-year research program to address the most common causes of death, disability and poor quality of life in post-menopausal women – cardiovascular disease, cancer, and osteoporosis. The WHI was launched in 1991 and consisted of a set of clinical trials and an observational study. The clinical trials were designed to test the effects of post-menopausal hormone therapy, diet modification, and calcium and vitamin D supplements on heart disease, fractures, and breast and colorectal cancer.

The hormone trial had two studies: the estrogen-plus-progestin study of women with a uterus and the estrogen-alone study of women without a uterus. (Women with a uterus were given progestin in combination with estrogen, a practice known to prevent endometrial cancer.) In both hormone therapy studies, women were randomly assigned to either the hormone medication being studied or to placebo. Those studies ended several years ago, and the women are now participating in a follow-up phase, which will last until 2010.

Estrogen plus progestin trial (stopped in July 2002)

Compared with women in the placebo those on estrogen plus progestin had:

  • Increased risk of heart attack
  • Increased risk of stroke
  • Increased risk of blood clots>
  • Increased risk of breast cancer
  • Reduced risk of colorectal cancer
  • Fewer fractures
  • No protection against mild cognitive impairment and increased risk of dementia (study included only women 65 and older)
  • Increased risk of dying of lung cancer

Women’s Health Initiative memory study (stopped in May 2003)

  • Women taking hormones had twice the risk for developing dementia
  • Hormones provided no protection against mild cognitive impairment/memory loss

Estrogen-alone trial (stopped in February 2004)

  • Estrogen increased risk for stroke
  • Estrogen decreased risk for hip fracture
  • No positive or negative effect on breast cancer

Compared to placebo women on estrogen alone had:

  • Increased risk of stroke
  • Increased risk of blood clots
  • Uncertain effect for breast cancer
  • No difference in risk for colorectal cancer
  • No difference in risk for heart attack
  • Reduced risk of fracture

Links to Research Information

Estrogen Plus Progestin Trial: July 2002
The Women’s Health Initiative Memory Study: May 2003
The Estrogen-alone Trial: February 2004

_______________________________________________

† Deep vein thrombosis refers to a blood clot deep inside the veins, usually in the legs.
‡ Symptoms include thinning and inflammation of the vaginal walls and changes in the vulva.

Does abortion cause breast cancer?

No. Although there has been a great deal of controversy on this topic, scientists have agreed that abortion does not cause breast cancer.

The world’s leading experts, including epidemiologists, clinical researchers, and basic scientists, have discussed the scientific data on reproductive events in a woman’s life that could affect her risk of developing breast cancer. They evaluated the research that has been done on this topic and concluded that abortion and miscarriage do not increase a woman’s risk of breast cancer.

Breast cancer is related to reproductive experiences such as age of puberty and age of motherhood, and for years anti-abortion activists have cited research showing a link between abortion and breast cancer. That research has been quoted by some politicians as evidence that should be provided to women to discourage abortions. A workshop was held in 2003 (during the Bush Administration) at the National Cancer Institute (NCI) as a result of this controversy, and despite political pressures it concluded that the research linking breast cancer and abortion is flawed and not as credible as research indicating that there is no link between breast cancer and either abortion or miscarriage.

A medical journal article published in 201511 evaluated 15 studies on this issue, which included 31,816 women with breast cancer from seven studies in the U.S., seven studies in Europe, and one in China, conducted between 1986 and 2013. The scientists only evaluated studies which used the most reliable research design (what is known as a “prospective study”) and concluded that the evidence does not show a link between cancer and abortion.

The fact that abortion does not increase the risk of breast cancer is also supported by, among others, the World Health Organization (WHO), the National Cancer Institute and the American Cancer Society, as well as many women’s health advocacy organizations, including the National Breast Cancer Coalition, the National Women’s Health Network and Our Bodies Ourselves.

For more information on the NCI workshop and early reproductive events and breast cancer, please see: http://cancer.gov/cancerinfo/ere.

 

Morcellation devices: a surgical tool that can spread cancer? What you need to know

By Anna E. Mazzucco, Ph.D.
2014

If you have uterine fibroids and are considering treatment or if you’ve heard about uterine morcellation in the news, this article will help you understand the issue.

What are power morcellation devices?

A power morcellation device is a small surgical tool which cut tissue into smaller pieces.  This allows organs or other tissues to be removed through smaller incisions, making surgery shorter and leaving smaller scars behind.  The front end of a power morcellator has a spinning blade that cuts the tissue into tiny pieces (pulverizes it), and the back end is connected to a tube which sucks the tissue through the device (see image below).

morcellator

Power morcellation devices were originally designed for removal of the uterus (or the womb), but are currently used for many different types of surgical procedures because they make it easier for a physician to perform surgery using smaller incisions.

What is the controversy about morcellation devices?

In 2012, two Harvard doctors had their lives tragically affected by these devices.  Dr. Amy Reed, an anesthesiologist at Beth Israel Deaconess Medical Center, which is affiliated with Harvard Medical School, had surgery in the fall of 2013 to remove her uterus due to fibroids.  After the surgery she was diagnosed with advanced (stage IV) uterine cancer, spread by the use of power morcellation during her surgery.  The morcellation left behind tiny pieces of tumor throughout her pelvic cavity, which allowed the cancer to spread.  While morcellation devices are sometimes used with a bag to contain the fibroid or tissue so that it won’t spread, the bags can be difficult to use so not all surgeons use them.   Dr. Reed was never told that morcellation would be performed during her surgery, or about the potential risks.

As a result of this surgical procedure with morcellation, a small cancer that could have been easily and completely removed through surgery has been spread and is now considered fatal.

Dr. Reed, who is now undergoing aggressive treatment for her metastasized uterine cancer, and her husband, Dr. Hooman Noorchashm, who was a surgeon at nearby Brigham and Women’s Hospital (also affiliated with Harvard), began a campaign to raise awareness of this issue and prevent other patients from being harmed.  As a result, Brigham and Women’s Hospital has since changed its policies on use of morcellation.  Since their story came out, other similar stories have surfaced, confirming that cancer has been spread by these devices, that it is not a rare event, and that it can have fatal results.  Moreover, many of these patients had not been told about these potential risks before their surgeries, and in some cases weren’t even told that morcellation would be used.  In May 2015, the Wall Street Journalreported that the FBI is investigating whether information about the risks of morcellation was not reported by hospitals, doctors, and device makers, as required by law.

What are uterine fibroids?

Uterine fibroids are non-cancerous (benign) growths on the uterus.  They are very common among women, especially during and after the reproductive years.  In many women, they do not cause any noticeable symptoms or problems.  But in some women, uterine fibroids can cause pain, discomfort during sex, and heavy bleeding.  To read more about fibroids and treatment options for them, read our in-depth article here.

What are the risks and benefits of using power morcellators?

Morcellation can allow surgeons to do shorter, less invasive surgeries.  This can reduce the chances of excessive blood loss and infection, and can reduce the amount of time spent in the hospital and result in an easier recovery afterwards.  However, in the case of fibroids, there is no way to rule out the chance of hidden cancer which could be spread by morcellation.  The Food and Drug Administration (FDA) estimates that 1 in 350 women receiving surgery for uterine fibroids has a hidden cancer that could be spread by morcellation. This is why the FDA released a warning in April 2014 recommending against morcellation for uterine fibroids.

On July 10-11, 2014, the FDA held a public meeting to discuss the risks and benefits of these devices.  Our testimony before the FDA panel on uterine morcellation, is here.

On November 24, 2014 the FDA announced that they were issuing an immediate change in the label for power morcellation devices, which will now include a black box warning as follows:

“Uterine tissue may contain unsuspected cancer. The use of laparoscopic power morcellators during fibroid surgery may spread cancer and decrease the long-term survival of patients. This information should be shared with patients when considering surgery with the use of these devices.”

These tragic events involving power morcellation devices raise questions about how medical devices are approved and monitored, and how a tragedy like this can be prevented in the future.  If larger studies had been done before the FDA allowed these devices to be used, and if cases of cancer being spread by morcellation had been reported to the FDA by doctors and companies, the FDA could have warned doctors and patients much earlier and prevented women from being exposed to these risks.

What do patients need to know?

If you are considering surgical treatment for uterine fibroids, be sure to discuss morcellation with your surgeon and make your wishes clearly known.  Depending on your particular situation, there are alternative surgical procedures, such as vaginal hysterectomy, which can be done without morcellation.  For any surgical procedure, make sure you have a clear and thorough discussion with your doctor about exactly how the procedure will be done, what choices you have, and what the risks and benefits of different options are.   If you feel that you are not getting enough information from your doctor, consider getting a second opinion.  Be sure to ask your doctor how often they perform the procedure you will have, because patients usually have a better outcome from surgery if the doctor performs the exact same surgery frequently.  If the physician does not have many years of frequent experience with the surgery, seek out a doctor who does.  For more tips on how to make smart decisions about medical treatments, especially use of medical devices, read our article here.