Category Archives: Breast Cancer

Statement of Dr. Diana Zuckerman, President, National Center for Health Research, March 8, 2023

Breast Cancer, Breast Cancer, news-you-can-use, Other Cancers, Other Cancers

Today the FDA announced that 19 women were reported in medical publications who developed squamous cell carcinoma (SCC) in the capsule around breast implants. This is more than the 10 women that FDA reported in September. Several of the women died.  It is important to know that 24 cases of SCC have been reported to the FDA, but it is not known if these cases overlap with the 19 that were published or if some of the 24 cases were reported more than once. Some of the women had silicone gel implants, some had saline implants, some textured, some smooth.  Some of the women got breast implants for augmentation, others for reconstruction after mastectomy.  That means that all women with breast implants need to be aware of this risk, even though it may be rare.

Last September, the FDA also reported 12 cases of lymphomas different from anaplastic large cell lymphoma (ALCL) that were also caused by breast implants.  The agency has not updated those numbers.

Statement on Keytruda for Early Stage Triple Negative Breast Cancer

Breast Cancer, Breast Cancer, Testimony & Briefings, , ,

February 9, 2021

The National Center for Health Research is a nonprofit think tank that scrutinizes the safety and effectiveness of medical products.  We don’t accept funding from companies that make those products, so we have no conflicts of interest.  We welcome the opportunity to provide our views on Merck’s application for approval of Keytruda for the indication of high-risk early stage triple negative breast cancer.

Triple negative breast cancer has a lower survival rate than other breast cancers.  However, chemotherapy clearly improves 5-year survival.  Patients need additional treatment options but the bottom line for patients is that FDA should not approve an indication that is not proven to have clinically meaningful benefits, especially when the treatment has clear risks.   

The first issue to address is whether there is evidence that immune checkpoint inhibitors (ICIs) are effective for TNBC.  We agree with FDA scientists that “there is still uncertainty regarding ICIs for TNBC” based on the results from several clinical trials.

  • KEYNOTE-119 failed to meet its primary OS endpoint. 
  • KEYNOTE-355 has not met its OS endpoint. 
  • IMpassion130: clinical benefits need to be confirmed
  • IMpassion131 interim OS results favored control group

The second major issue pertains to pCR data in the study.  The results indicate only 7.5% improvement in pCRs at IA3 (the most recent interim analysis), which the FDA scientists point out may not be clinically meaningful even if statistically significant.  We agree.  The problem is that it is impossible to determine how this slight improvement would affect overall survival, and even if it does, how much neoadjuvant and adjuvant use each contribute to any benefit. 

FDA scientists were clear to the sponsor that there were concerns with their study design and that the application for approval was premature since the study was not yet completed.  The agency made it clear that that the event free survival (EFS) study results were not statistically significant, not clinically meaningful, and did not show a “stable trend.” 

FDA reviewers are clear that data on overall survival “are too immature to provide a conclusive interpretation regarding the difference in OS between treatment arms.” 

What about safety?

At IA3 (the most recent interim analysis), there were 96 deaths, which FDA points out “accounts for only 32% of the events needed for the final analysis. Therefore, the OS estimate may be unreliable, and the treatment effect size reported is subject to uncertainty.”

It is notable that the study included patient-reported outcomes (PROs), but unfortunately, KEYNOTE-522 was not designed to compare differences in PROs (symptoms, side effects, health-related quality of life), nor were these patient-reported endpoints prospectively identified and statistically tested. 

PRO assessments should have been more frequent, both for neoadjuvant and adjuvant treatments

Since many high-risk, early-stage TNBC patients will be cured with standard therapy, the key issue is whether this drug has benefits that outweigh the risks.  The benefits are unclear.  Therefore, the evidence of the drug’s “added toxicity” is worrisome.  FDA scientists concluded that “Some of these toxicities may be irreversible or require lifelong medication in patients cured of their breast cancer.

Although the sponsor counted 2 deaths due to immune-mediated adverse events, the FDA counted 4.  Either way, these deaths must be considered worrisome given the lack of clear evidence of a meaningful benefit.  And, there are many other serious adverse events in addition to the small number of deaths.   All-grade and grade ≥3 immune-mediated AEs and infusion reactions occurred more frequently in Keytruda patients compared to placebo:    43% vs. 22% for all grade AEs, and 15% vs. 2% for high grade AEs.  In fact, 10% of Keytruda patients had immune-mediated AEs and infusion reactions leading to hospitalization compared to 1% of placebo.  These included the following relatively high number of adverse events:

  • Infusion reactions (18%), 
  • Hypothyroidism (15%), 
  • Severe skin reactions (6%)
  • Hyperthyroidism (5%), adrenal insufficiency (3%), pneumonitis (2%), and thyroiditis (2%).

It is important to note that these adverse events were not resolved at the last assessment in the study for 19% of Keytruda patients.   It is also important to note that 16% of the Keytruda patients initiated thyroid hormone replacement during the study.

In summary, we agree with FDA scientists that the deaths are “particularly concerning in this curative disease setting.”

  • “All grade and grade ≥3 immune-mediated AEs were increased in [Keytruda] patients.’
  • Some “may be severe or lifelong.” 
  • The adjuvant treatment has fewer adverse events but “has not demonstrated a significant effect on any efficacy endpoint, and may be adding risk without benefit.”

Based on our analysis, we agree with the overall conclusions made by FDA scientists: 

  1. Neoadjuvant Keytruda “confers only a small absolute improvement in pCR rate of questionable clinical meaningfulness.”
  2. Event-free survival and overall survival are “immature and unreliable.”
  3.  “The design and results of KEYNOTE-522 do not currently support a role for adjuvant [Keytruda].”
  4. “Supportive data of clinical benefit … are lacking.” 
  5. Adding Keytruda “is associated with increased toxicity … which may be severe, irreversible, and/or require life-long medication in potentially curable and otherwise healthy patients.” 

In conclusion, the FDA and the medical community do patients no favors to approve a treatment that is not proven to benefit them and at the same time is proven to cause harm for a substantial percentage of patients.  The studies should be continued to determine whether the benefit of adding Keytruda to other treatments outweigh the risks.

 

This written statement was submitted to the FDA on February 8, 2021 and an oral version with PowerPoint slides was presented at the FDA Advisory Committee meeting on February 9, 2021.

We are pleased that the FDA Advisory Committee agreed with our views and voted 10-0 on February 9 in favor of deferring an FDA regulatory decision until the study is completed.

Dr. Diana Zuckerman’s Statement on FDA’s Draft Guidance on Labeling for Breast Implants

Breast Cancer, Breast Cancer, Policy, Press Releases, Testimony & Briefings

Statement of Dr. Diana Zuckerman, President, National Center for Health Research on October 23 Regarding FDA Labeling Recommendations to Improve Patient Communication Draft Guidance

We thank the FDA for proposing a black box warning and a patient Informed Consent check list that provides specific, understandable information about the risks of breast implants.  The FDA’s draft includes the types of information that we have proposed to the FDA in recent months in our work with patient advocates and plastic surgeons.  The devil is in the details, so we look forward to working with the FDA to finalize these materials so that patients can make better informed decisions in the future than most women considering breast implants have been able to make. We will  keep working closely with the FDA, patients, and plastic surgeons to make that goal a reality.

For more information see FDA’s Draft Guidance here.

Insurance Coverage Information for Breast Implant Removal

Breast Cancer, Breast Cancer, Treatment & Management

The original reason for getting your breast implants matters to health insurance companies (as well as Medicare and Medicaid).  If your implants were put in after a mastectomy and your doctor believes that removing your implants is “medically necessary,” then your health insurance is legally obligated to cover your breast implant removal under the Women’s Health and Cancer Rights Act of 1998 (WHCRA).

If the original reason for getting breast implants was for augmentation of healthy breasts, then some health insurance companies will cover your explant surgery if they consider the services to be “medically necessary.”

What are “Medically Necessary” Services?

Insurance companies cover services that they determine to be “medically necessary” to treat a disease or illness. Although you or your doctor may believe a service is medically necessary, insurance companies don’t always agree.

Most insurance companies will not cover any cosmetic procedures and some will not cover complications from previous cosmetic procedures.  However, many companies consider removal of breast implants medically necessary for patients with any of these conditions:

Unfortunately, insurance companies usually won’t cover the cost of breast implant removal for autoimmune or connective tissue diseases or other systemic complications. If you have any of the conditions listed in the bullets above, you should focus on those in your insurance claim because insurance companies are more likely to cover these symptoms.

How do I know whether my insurance company will cover the cost of removal?

To find out if your insurance company is likely to cover removal, you will need to look at your specific policy language. You can usually find this language in a document called “Evidence of Coverage” (EOC), this is also sometimes called a “Benefits Booklet.” It is a document (typically about 100 pages) that describes in detail the healthcare benefits covered by your health plan, including procedures that your insurance company will and will not cover.

You can access an electronic copy of your EOC through your online account on your insurance company’s website. You can also call the member services number on the back of your insurance card and ask an insurance representative for a copy of this document.

What Do I Look For?

Once you have your policy, look for language about breast implant removal.  If you don’t see any language about breast implant removal, search for language on complications from cosmetic surgery. If you cannot find any specific language about breast implant removal, you should also look to see what your insurance company’s definition of “medically necessary” is. It is also important to check whether your insurance plan requires pre-authorization for any surgeries.

If you’re using an electronic copy, you don’t need to read the entire document. You can easily find terms using the “Control+F” keys on your keyboard. That will provide a “search box” that will search for any words you enter. Just enter the word “breast” or “cosmetic” or “medically” in the search box. If you are unable to find what you need in the lengthy document, call your member services line and ask for assistance to locate the correct pages.

File for Pre-Authorization

Most insurance companies will require that you get pre-authorization (also called prior approval or pre-certification) before the surgery. This means your insurance company reviews your relevant information and determines whether surgery is medically necessary. Then, the insurance company will let you know if it is likely to cover your surgery. However, that pre-authorization isn’t a promise that your surgery will be covered.

The easiest way to get pre-authorization is to have your plastic surgeon sign and submit a letter that lists your symptoms and explains why removal is medically necessary based on your insurance policy language. (Usually one or more of health problems listed on the bullets earlier in this article). Your surgeon should also enclose any medical documentation that provides proof of your symptoms.

It is best if your plastic surgeon signs this letter to send with your insurance claim. However, if your surgeon is unwilling to sign the letter, another doctor involved with your care, such as your primary care provider, can sign. You can find templates for these letters here. If your doctor agrees to sign the letter, but won’t submit it to your insurance company, you will need to submit the letter before your surgery to ensure you receive pre-authorization.

NOTE: If you don’t get pre-authorization when it was required, the insurance company isn’t required to cover the surgery, even if it considers the procedure to be medically necessary.

After Your Surgery: Filing a Reimbursement Claim

If your surgeon is in your insurance company network, he/she should file a claim on your behalf. If not, you will have to pay upfront for the surgery and file the reimbursement claim with your insurance company. Even if you see a surgeon who doesn’t take insurance, you should still file a pre-authorization claim with your insurance company. If you didn’t seek pre-authorization before your surgery, you can still file a reimbursement claim.

In your reimbursement claim, you will need to submit your pre- and post-operative reports, along with a letter from the surgeon stating that the procedure was medically necessary.

You can learn more about getting private insurance to cover your explant surgery, including how to appeal a denial, here on our breast implant information website. 

What if I have Medicare?

Medicare usually covers breast implant (saline or silicone) removal for any of these conditions:

  • Painful capsular contracture with disfigurement
  • Implant rupture
  • Infection
  • Implant extrusion (coming through the skin)
  • Interference with the diagnosis of breast cancer
  • Siliconoma or granuloma (silicone-filled lumps under the skin)
  • Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), a cancer of the immune system)

Medicare coverage can differ depending on the state where you live. You can check the specific Medicare policies on breast implants removal in your state here.

You can learn more about getting Medicare to cover your explant surgery here on our breast implant information website. 

You can learn more about getting Medicaid to cover your explant surgery here on our breast implant information website. 

What do I Need to Know about Breast Implant Removal Surgery?

See our article here.

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

NCHR Statement on FDA’s Request for Recall of Allergan Breast Implants and Expanders

Breast Cancer, Breast Cancer, Policy

Statement of Dr. Diana Zuckerman, President, National Center for Health Research on July 24 Announced Recall of Allergan Biocell Breast Implants and Expanders

h Research on July 24 Announced Recall of Allergan Biocell Breast Implants and Expanders

“The FDA announced today that at its request, Allergan is implementing a worldwide recall of their Biocell textured breast implants and expanders.  This recall is an important step toward reducing the risk of a type of cancer of the immune system called Anaplastic Large Cell Lymphoma (ALCL) caused by breast implants.  Many other countries had already banned this type of Allergan textured breast implant, but the FDA had previously stated that such a ban was premature.  However, it was inevitable that 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.  It is a little surprising that the FDA is taking credit for the recall, since most recalls of medical devices are described by the companies as voluntary.

“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.  This recall will reduce that risk but it won’t eliminate it.”

For more information, see the FDA’s Press Release here.

Breast Reconstruction Options After Mastectomy

Breast Cancer, Breast Cancer

Many breast surgeons and breast cancer patients believe that breast reconstruction is an important step in recovering physically and mentally from a mastectomy.  Research shows that women who undergo flap procedures (described below) have a better quality of life after reconstruction than women undergoing reconstruction with breast implants.1

However, not all women are able to undergo those procedures.  Unfortunately, many patients are not given complete information about the different options for breast reconstruction, including the risks and benefits of each.  In fact, a 2017 study showed that only 43% of mastectomy patients received the information and counseling necessary to make an informed decision regarding their reconstruction choice.2

The Women’s Health and Cancer Rights Act of 1998 is a law that requires that private insurance companies pay for breast reconstruction if they pay for mastectomies.  This includes reconstruction on the removed breast, modification of the other breast to create a symmetric appearance, and treatment of any complications that result from a mastectomy or reconstruction.  The forms of reconstruction covered may vary by state and insurance provider, so it is important that you call your insurance provider to see which options will be covered in your particular case.3

This article does not provide medical advice, but we provide information based on scientific research and from speaking to many experts in the field.  We recommend discussing your treatment options with a physician whom you trust.  As a patient, you have the right to seek more than one medical opinion.

Which Type of Breast Reconstruction is Best?

The decision of which reconstruction option to choose, if any, is a personal one.  To make an informed choice, however, patients need to meet with breast surgeons who are skilled at the different options.  Since most breast surgeons only know how to do reconstruction with breast implants, they don’t usually provide good information to their patients about the benefits of other options.

There are several studies which look at the long-term outcomes for each of the reconstruction options, and these can help patients to make a decision.

For example, a study published in 2018 analyzed over 2000 reconstruction patients and found that patients who undergo autologous breast reconstruction (“flap” procedures) are generally more satisfied in the long-term than women who choose reconstruction with breast implants.  After two years, patients who chose to get flap procedures reported having a better quality of life than patients who got breast implants.  Some of the areas in which the flap patients reported greater satisfaction include their psychosocial, physical, and sexual well-being.4

The researchers also found differences in surgery-related complications within the first 2 years after surgery.  Flap procedures have significantly higher rates of short-term surgery-related complications that occur immediately following surgery.  In contrast, breast implants have more surgery-related complications that occur weeks or months after the surgery is completed. 5 In addition, women are likely to need multiple surgeries to replace implants over their lifetime.6

A description of the options for reconstruction is below.

Reconstruction with Breast Implants

Breast implants are the most common form of breast reconstruction after mastectomy.  7 This is probably because breast implants are the easiest form of reconstruction and most plastic surgeons are not skilled enough to perform the other types of breast reconstruction discussed below.  There are silicone gel breast implants and saline breast implants on the market, and both options have a high complication rate for reconstruction patients.  You will probably be told that breast implants are not lifetime devices, but that’s an understatement.  Studies by researchers and by implant manufacturers have shown that after three years, most reconstruction patients will have at least one serious complication.8,9

Below are some of the most common complications of breast implants.

In addition, women who have breast implants, either for mastectomy or healthy breasts, are more likely to develop a type of lymphoma (cancer of the immune system) called ALCL.17

You can read more about risks and complications related to breast implants here and more about the different types of breast implants here.  Despite the risks, some women get implants because they are not good candidates for other types of breast reconstruction.  Women who are very thin or very physically active, have poor veins, or who may become pregnant in the near future may not be good candidates for other reconstruction options.

Reconstruction with Autologous Tissue Transfer (Flap Procedures)

Autologous tissue transfer (also known as a flap or flap procedure) refers to any procedure in which the body’s own tissue is used to reconstruct breasts.  Surgeons take fat and other tissue from another part of a woman’s body and move it to create breasts.  Sometimes, implants are used along with the tissue transfer to create larger breasts.  When implants are used with flap procedures, the risk for complications is higher than for either procedure alone.  For that reason, it makes sense to choose either flap reconstruction or implants but not both.

There are various types of autologous tissue transfer as described below.

Flap Reconstruction with Muscle and Fat

In this procedure, surgeons take muscle and fat from other areas of the body and move it to the breast area.  The most common form of this procedure is the TRAM flap, which uses muscle and fat from the abdomen.  While using stomach muscle is typical, surgeons can also take muscle from the inner thigh or buttocks.  Reconstruction methods using fat and muscle create a more natural looking reconstruction than those using only fat due to their added firmness.   Also, the larger amount of tissue used during muscle and fat reconstructions enables the surgeon to create larger breasts than those with fat only.  A drawback to this type of surgery is its complexity.  Veins and arteries must be reattached to the muscle and fat, so this surgery requires an experienced vascular surgeon.  Even with a good surgeon, this surgery isn’t 100% successful.  However, if it is successful, these reconstructed breasts can last a lifetime.   But, if muscle is removed from the abdomen, the women will not have as much strength there as they did before.18

Flap Reconstruction with Fat Only

Some reconstructions are performed using only fat.  The most common form of this is the DIEP flap, which takes skin, vessels, and fat from the abdomen but spares the muscles.  Surgeons can take tissue from most areas of the body that have a large fat supply.19 Reconstruction with only fat takes more time than other procedures because the tissue has to be harvested and removed from the body before the reconstruction can take place.20 To be a good candidate for this procedure, women need more body fat to create the breast.  This means that women with low body fat or poor vascularity may not be good candidates for this surgery.  The difficulty of this form of reconstruction are similar to those of reconstructions done with muscle and fat.  However, since no muscle is used, patients should not expect to permanently lose strength in any part of their body.21

Reconstruction with the Latissimus Dorsi

This surgery, commonly known as Lat flap, uses the latissimus dorsi muscle to reconstruct breasts.  The latissimus dorsi is a muscle of the upper back that extends around the side of the body. This procedure is more likely to fail than some other flap procedures, but less likely to have surgery-related complications or need reoperations within the first two years.22

Lat flap can be performed on women who do not have enough body fat for other forms of autologous reconstruction, and is frequently used with breast implants.  Some surgeons prefer it because the only visible scar will be from the mastectomy, and because the muscle can remain attached to its original blood source, which lowers the chance of the tissue dying after transfer.  However, since the latissimus dorsi is a large and important back muscle, the procedure can lead to serious difficulties moving, lifting, or performing strenuous exercise.  Patients who choose this option can also expect to get fatigued more easily.23

It’s Your Choice

As you can see from the research above, flap procedures are a very good choice for women who want a lifetime solution that avoids the complications typical of breast implants, and the possible risk of developing lymphoma.  However, fewer doctors perform flap procedures.  They are also longer and more complicated surgeries than reconstruction using breast implants.  For this reason, it is extremely important that women choosing a flap procedure go to a surgeon who is very experienced in autologous reconstruction.

When making a reconstruction decision, it is important for each woman to weigh the risks and benefits of each procedure with a doctor that is capable of these different options, so that she can make a decision that is right for her.

We hope this information is helpful. For more information, check out http://www.breastimplantinfo.org or feel free to write to us at info@center4research.org / info@stopcancerfund.org

The comments and statements of the National Research Center for Women & Families are believed and intended to be accurate, and where applicable, based on scientific literature. NRC’s statements do not constitute medical diagnoses, medical advice, plans of treatment, or legal opinion, and we are not responsible for the use or application of this information. All medical information should be reviewed with your health care practitioner.

We hope that the information we’ve provided is helpful. In order to maintain this free service to all women and their families, we invite your tax-deductible contributions to NRC (see http://www.center4research.org/contribute/ )

Patient Satisfaction After Breast Reconstruction with Implants Compared to Flap Procedures

Breast Cancer, Breast Cancer

 

For many women, breast reconstruction can be an important step in recovering physically and mentally after a mastectomy.  However, research shows less than half of mastectomy patients received the information and counseling necessary to make an informed decision regarding their reconstruction choice.

A 2018 study by Katherine Santosa and her colleagues found that patients who undergo autologous breast reconstruction (also called “flap” procedures), are generally more satisfied in the long-term than women who choose reconstruction with breast implants.  The study included 2,013 patients, 74% of whom got breast implants and 26% of whom had autologous reconstruction. Autologous tissue transfer refers to any procedure in which the body’s own tissue is used to reconstruct breasts. Surgeons take fat and other tissue from another part of a woman’s body, usually the abdomen, and move it to create breasts.

The researchers surveyed women on their quality of life 90 days before their mastectomy, and at 1, 2, 3, and 4 years after reconstruction. The survey included questions on four topics: Patients’ satisfaction with their breasts, emotional and social well-being, sexual well-being, and physical well-being. In the satisfaction with breasts category, women were asked questions about their breasts appearance, their satisfaction with breasts and how bras fit, and how the breasts feel to the touch. To understand women’s emotional and social well-being, researchers asked questions about body image and a woman’s confidence in social settings. Women were also asked about their sexual well-being, including questions about feelings of sexual attractiveness, sexual confidence, and comfort level during sex. Lastly, researchers asked women about their physical well-being, including information about pain, tightness, and any physical difficulty with performing daily activities.

Patients who chose autologous reconstruction reported higher satisfaction with their breasts than those who got breast implants. The women who had autologous reconstruction also reported greater emotional and social well-being and sexual well-being compared to before reconstruction. In contrast, patients who got breast implants reported worsened sexual well-being compared to before reconstruction.

The information from this study can provide useful information to patients and their doctors about patients’ likely quality of life following breast reconstruction with autologous or “flap” procedures compared to breast implants.

You can read a summary of the original article here.

Reference:

  1. Santosa, Katherine B et al. Long-term Patient-Reported Outcomes in Postmastectomy Breast Reconstruction. JAMA Surgery. 2018; 153(10): 891 – 899.

Summary of Published Study by MD Anderson Physicians on the Increase in Rare Diseases Among Women with Breast Implants

Breast Cancer, Breast Cancer, New Cancer Research

National Center for Health Research: September 17, 2018.

A study published in September 2018 in the medical journal Annals of Surgery, entitled US FDA Breast Implant Postapproval Studies: Long-term Outcomes in 99,993 Patients, concluded that “silicone implants are associated with an increased risk of certain rare harms” and that further study is needed “to inform patient and surgeon decision-making.” Also, the study was published on social networks and became more visible with many subscribers and comments which were provided by The Marketing Heaven. The study is important because it is largest study to date, but it has limitations because it is based on data from flawed studies conducted by two implant companies, Mentor and Allergan.

The data collected from the two studies were supposed to be very similar, but because of how poorly the studies were conducted, they are not comparable.  Mentor’s data are focused on patients’ self-reporting on questionnaires, primarily on data of only 20% of the patients collected 7 years after the study was started. Allergan’s data are based on physicians’ diagnoses during the first two years after the patients had implant surgery.  Since patients’ self-reports at 7 years would be expected to include more complications than physicians’ diagnoses after 2 years, it is impossible to make meaningful comparisons between the two manufacturers. Nevertheless, it is important to note that the MD Anderson researchers found that the risks of certain autoimmune diseases increased by 800% (Sjogren syndrome), 700% (scleroderma), and 600% (arthritis) for the women with Mentor silicone gel breast implants compared to the general population of women of the same age and demographics.  Stillbirths increased by 450% in the women who became pregnant.  Other autoimmune and rare diseases were also significantly higher among women with Mentor silicone gel implants.  These diagnoses were also statistically significantly higher (although not as dramatically increased) for women with Allergan implants compared to the general population of women of similar demographics. Given the large percentage of women who were not in the study for more than 1 year, it is not possible to know how representative these findings are. However, these results certainly deserve careful attention.

It is also important to note that the women with saline breast implants who were in the Mentor and Allergan studies were not analyzed in the MD Anderson study.

FDA Response

In response to this important study, Dr. Binita Ashar of the FDA published an editorial in the same issue of the same medical journal, claiming that the MD Anderson study “failed to account for methodologic differences between studies, inconsistencies in the data, differential loss to follow-up, confound and other potential sources of bias.”  That is true.  However, Dr. Ashar did not mention that the FDA should take responsibility for all the shortcomings of the data that MD Anderson analyzed.  She did not mention that the flawed data were based on studies that were required by the FDA as a condition of approval for the breast implants made by Allergan and Mentor.  The data were flawed because women soon disappeared from the study, and the FDA did not require the companies to finish the studies, as they should have,

As a result of the FDA’s failure to enforce the study requirements, the large Allergan and Mentor studies used as the basis of the MD Anderson analyses were very flawed short-term studies rather than the 10-year studies that FDA had proudly said they were requiring.  Whereas the companies blamed the study shortcomings on the enormous number of women who “dropped out” of the study shortly after enrolling (including 80% of the women with Mentor implants after only 1 year), we have interviewed women who were enrolled in those studies who told us that they did not drop out of the studies – rather they were “dropped” from the study by the researchers without their consent.  They never heard from the researchers and hence had no opportunity to tell the researchers how sick they had become after getting breast implants.   Instead, several of those women went to the FDA this month to explain to FDA scientists what happened.  They told Dr. Ashar and other FDA officials that they were dropped from the studies.  They told Dr. Ashar and other FDA officials that they had suffered from autoimmune and connective tissue symptoms such as the ones reported in the MD Anderson study.  They told Dr. Ashar and the other FDA officials that despite being sick for years, they were unaware that breast implants could be the cause because neither the FDA nor their plastic surgeons had warned them of the risks.  When they finally found each other on social media (on Facebook pages joined by more than 50,000 women harmed by breast implants), they realized that removing their implants might help.  Much to their surprise, they experienced almost miraculous recoveries after their implants were removed by experienced explant surgeons.   The women told Dr. Ashar and other FDA officials that their symptoms disappeared entirely or improved by 85%.

The FDA editorial was written before Dr. Ashar met with the former implant patients this month, but she had previously met with several of the same women who had reported these same problems and recoveries after explant surgery.  So it is very discouraging that FDA staff have been and continue to be so close-minded about the risk of breast implants despite the MD Anderson analyses.

What Have we Learned from the MD Anderson Study?

We agree with the FDA and the MD Anderson researchers that these results can’t be considered conclusive, but the FDA needs to look at the data more carefully and require better studies so that they can reconsider their repeated claim that breast implants are only proven to cause local complications, such as leaking and painful implants.  Although the FDA admits that breast implants can cause a cancer of the immune system known as ALCL, they continue to quote industry-funded studies claiming that implants do not cause other systemic illnesses.  It should be obvious to open-minded scientists that if breast implants can cause cancer of the immune system, they can probably cause other serious immune system diseases and symptoms.  Moreover, the results of the MD Anderson study supports those concerns about autoimmune symptoms and diseases.

What should be the key information of importance to women considering breast implants or women who have them in their bodies? Clearly, these studies indicate that patients should report any new symptoms that develop after getting their implants, whether involving their breasts or other parts of their body.  Breast implant patients should know that the FDA recommends MRI imaging of silicone breast implants 3 years after the augmentation or reconstructive surgery and every 2 years thereafter.

  

Statement of Dr. Diana Zuckerman, President of the National Center for Health Research Regarding the New Study of 100,000 Women with Breast Implants

Breast Cancer, Breast Cancer, In the News, Press Releases

Dr. Diana Zuckerman, President of the NCHR: September 17, 2018.

In the largest study ever conducted of long-term health risks for patients with breast implants, researchers at The University of Texas MD Anderson Cancer Center have reported that women with silicone implants are more likely to be diagnosed with several rare diseases, autoimmune disorders, and other conditions.  These results are consistent with numerous previously published studies, but contradict the conclusions of studies funded by implant manufacturers or plastic surgery medical societies.

The study, published in the medical journal Annals of Surgery, is by researchers in MD Anderson’s Department of Plastic Surgery and is based on analyses of almost 100,000 patients with either saline or silicone implants. The information was derived from the FDA’s database dating back to 2005.  When the FDA approved silicone gel breast implants made by two manufacturers in 2006, the agency required that each of the manufacturers study at least 40,000 women for 10 years.  Those studies were started but never completed, making it impossible to determine the long-term risks of breast implants.  In the absence of such crucial studies, patients report that they were not warned about the risks when they decided to get breast implants.

We thank Mark W. Clemens, M.D., associate professor, Plastic Surgery, the senior investigator of this very important study.  The findings are consistent with what thousands of women with breast implants have reported in Facebook groups and other social media, and directly challenge the FDA’s claims that breast implants do not cause such diseases.  We urge the FDA to be more patient-centered and finally require independent studies be conducted of women before and after their breast implants are removed.  Many women have reported that their debilitating autoimmune symptoms decreased or disappeared after their breast implants were removed, but scientific data is needed to establish the rate of recovery.

Radiation Therapy for Ductal Carcinoma In Situ (DCIS)

Breast Cancer, Breast Cancer, General Treatment Issues, Medical Treatments with Cancer Risks

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, as is hormonal therapy (such as tamoxifen) if the DCIS is estrogen-receptor positive. 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  However recommendations for radiation therapy are changing.

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.

The Van Nuys Prognostic Index incorporates four independent factors that predict local tumor recurrence (tumor sizes, margin width, pathology grade and necrosis, and patient age). Experts recommend that women with DCIS with a low score (4–6) on this Index should undergo a lumpectomy alone without radiotherapy since the chances of recurrence are low, and there is no evidence that radiation would reduce the chances of dying from breast cancer. 5

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
  5. Wong JS, Kaelin CM, Troyan SL, et al. Prospective study of wide excision alone for ductal carcinoma in situ of the breast. J Clin Oncol. 2006;24:1031–1036.