Category Archives: Other Cancers

Breast Implants and Cancer of the Immune System (ALCL): A History of Who Knew What When

Maura Duffy, Cancer Prevention & Treatment Fund

Experts now agree that breast implants can cause a type of cancer of the immune system.  The FDA finally admitted this risk of cancer in 2017, but other experts – including plastic surgeons — were aware of the risk years before.  Why did it take so long for FDA, the media, and women with implants to find out that choosing breast implants could increase their chances of developing a potentially fatal disease?

Anaplastic large cell lymphoma (ALCL) is a rare type of cancer of the immune system that usually develops in the lymph nodes, skin, lungs, or liver. However, ALCL sometimes develops in the breast area of women with breast implants.

In 2008 Dutch researchers published a report of 11 women with breast implants and ALCL, and concluded that the implants seemed to be associated with ALCL.[3]  Although published in the Journal of the American Medical Association (JAMA), this information was not widely reported.

The link between ALCL and breast implants was first reported by the U.S. Food and Drug Administration (FDA) in January of 2011. In 2013, researchers at MD Anderson Cancer Center studied 60 women with breast implants who were diagnosed with ALCL in the breast. Since ALCL was thought to be diagnosed in only 1 woman in half a million, this was much higher than would be expected.[3] In 2014, the National Comprehensive Cancer Network (NCCN), a nonprofit network of cancer experts, released a worldwide oncology standard for surgeons and oncologists to test for and diagnose “breast implant associated ALCL (BIA-ALCL).  In 2016, the World Health Organization (WHO) officially named the disease “breast implant associated ALCL (BIA-ALCL)”.

And yet, it was not until March 2017 that the FDA finally updated its website to officially report that breast implants could cause ALCL. At the time of the FDA announcement, the agency reported that they had received 359 reports of ALCL among women with breast implants. Reports to the FDA of problems from medical devices are acknowledged to be the “tip of the iceberg” since surgeons frequently do not do these online reports.

How did women find out they had ALCL before the official announcement of BIA-ALCL was made? Most of them approached their doctors with symptoms such as pain, lumps, swelling, or asymmetry in their breasts years after getting implants.  Since breast implants are a “foreign body,” the body forms scar tissue around the implant to protect their body from this “foreign invader.”  The scar tissue surrounding the implant is known as the scar capsule. It is natural for the body to form scar tissue, and the scar tissue is only a problem if it tightens or hardens around the implants, causing pain and hardness known as “capsular contracture.”  Breast implant-associated ALCL is almost always found in the scar capsule surrounding the implant, not the breast tissue itself. It has been reported in women both with and without capsular contracture, as well as women with silicone gel or saline breast implants.[4]

ALCL is diagnosed by testing the fluid that collects around the implant, called a seroma.[5] Seroma is usually not caused by ALCL.  It is important to understand that even when ALCL is in the breast, it is not breast cancer, but rather a cancer of the immune system.  Most breast implant-associated ALCL has cancer cells within the fluid inside the scar capsule. That ALCL can be treated by removing the implant and the surrounding scar tissue. This surgery is known as a capsulectomy.

One study of nine women who had a capsulectomy after being diagnosed with BIA-ALCL found that all nine were disease free when they were studied 3.5 years later, and they did not require chemotherapy nor radiation treatment. However, some types of ALCL are more aggressive and need to be treated with chemotherapy or radiation. [6]

In December 2013, the study of 60 patients with breast implants and ALCL reported that the ALCL was more likely to be fatal for women who had a solid ALCL tumor than for women who had ALCL cancer cells in the surrounding fluid (known as effusion ALCL). All of the patients with effusion-type ALCL were still alive 5 years after their diagnosis, compared to only 75% of the patients with solid ALCL tumors. ALCL returned in only 14% of patients with effusion-type ALCL. Patients with solid ALCL tumors had a 50% recurrence rate.[7]

Longer studies with more patients are needed to determine if certain kinds of breast implants are more likely to cause ALCL.  Preliminary data indicate that most, but not all, women with BIA-ALCL had textured breast implants at some point.  Meanwhile, women with all types of implants should have routine follow-ups and should immediately see a doctor if one or both of their breasts become swollen.

For women with silicone implants, FDA recommends getting a breast coil MRI three years after getting the implants, and every two years after that.[8]

Although plastic surgeons and breast implant manufacturers admit that breast implants can cause ALCL, they claimed it was very rare.  For example, Allergan, a manufacturer of many different types of breast implants, claimed that “A woman is more likely to be struck by lightning than to get this condition.”[9]   However, 400 people are injured or killed by lightning every year,[10] which is why most people avoid situations where lightening can harm them.

In fact, the Australian version of the FDA now estimates that 1 in 1,000 women with breast implants will develop BIA-ALCL, [11] which is not nearly as rare as plastic surgeons and manufacturers have claimed.

Many women would not want to take the chance of developing cancer as a result of breast implants, and this is especially true for women who underwent mastectomies that were not medically necessary in an effort to reduce their chances of cancer returning.

It is also important to note that the link between breast implants and autoimmune diseases has been hotly debated for two decades, with many women reporting serious autoimmune symptoms that went away when their implants were removed.[11]  The scientific evidence regarding ALCL and implants once again raises questions about the possible impact of breast implants on autoimmune disease or symptoms such as joint pain, body pain, memory loss, and chronic fatigue.

For many years, women with breast implants were assured by implant companies, plastic surgeons, and the FDA that breast implants did not cause breast cancer or any other type of cancer. Evidence of a link to some types of cancer and to autoimmune diseases, including studies conducted by researchers at FDA and the National Cancer Institute, was dismissed. However, as everyone knows from data on lung cancer and smoking, it can take decades to determine if an exposure causes cancer or other serious diseases. Even a very strong carcinogen, such as tobacco, is very unlikely to cause lung cancer for at least 30 years.  For this reason, it is essential that physicians and researchers take a closer look at the link between breast implants and cancer of the immune system, as well as other immune disorders.

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

References

  1. Mazzucco, AE. Next Steps for Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol, 2014. Early release publication. June 16, 2014.
  2. S. Food and Drug Administration. 26 January 2011. Web. June 25, 2012, <http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm241090.htm>
  3. “Anaplastic Large Cell Lymphoma (ALCL) In Women with Breast Implants: Preliminary FDA Findings and Analyses.” January 2011. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Web. June 25, 2012, <http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/BreastImplants/ucm239996.htm>
  4. “FDA Questions and Answers about Anaplastic Large Cell Lymphoma (ALCL).” U.S. Food and Drug Administration. 26 January 2011. Web. June 25, 2012, <http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/BreastImplants/ucm241086.htm>
  5. Kim B, Roth C, Young VL, Chung KC, van Busum K, et al. Anaplastic large cell lymphoma and breast implants: results from a structured expert consultation process. Plastic and Reconstructive Surgery. 2011 Sep;128(3):629-39.
  6. Aladily TN, Medeiros JL, Amin, MB, Haideri N, et al. Anaplastic Large Cell Lymphoma Associated with Breast Implants: A Report of 13 Cases. Am J Surg Pathol. 2012 June 36(6).
  7. end Miranda, et al. Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients. J Clin Oncol. 9 December 2013.
  8. FDA Update on the Safety of Gel-Filled Breast Implants.” June 2011. Center for Devices and Radiological Health. U.S. Food and Drug Administration. Web. June 25, 2012, http://www.fda.gov/downloads/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/BreastImplants/UCM260090.pdf target=”_blank”>http://www.fda.gov/downloads/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/BreastImplants/UCM260090.pdf>
  9. Edwards, Jim. “Breast Implant Maker Challenges FDA on Cancer Link.” CBS Money Watch. 27 January 2011. Web. 25 June http://www.cbsnews.com/8301-505123_162-42847224/breast-implant-maker-challenges-fda-on-cancer-link/ target=”_blank”>http://www.cbsnews.com/8301-505123_162-42847224/breast-implant-maker-challenges-fda-on-cancer-link/
  10. Cooper, Mary Ann, MD. “Medical Aspects of Lightning.” National Weather Service. Web. 25 June 2012.http://www.lightningsafety.noaa.gov/medical.htm
  11. Mazzucco, Anna, Ph.D and Zuckerman, Diana, Ph.D. “ALCL and Breast Implants: 2017 Update.” Breast Implant Information. Web. March 14, 2017. <http://www.breastimplantinfo.org/implantalcl/>

ALCL and Breast Implants: 2017 Update

Anna E. Mazzucco, PhD and Diana Zuckerman, PhD, Cancer Prevention & Treatment Fund

In March, 2017, the U.S. Food and Drug Administration (FDA) updated its website to officially report that breast implants could cause a type of cancer of the immune system called anaplastic large cell lymphoma (ALCL).  They stated they have received 359 reports of ALCL among women with breast implants.

The FDA’s announcement came 10 months after the disease was named breast implant associated ALCL (BIA-ALCL) in a  World Health Organization publication in 2016, and a few months after the and the National Comprehensive Cancer Network (NCCN) released the first worldwide oncology standard for the disease.  NCCN includes a guided algorithm for surgeons and oncologists to test for and diagnose the disease.  They concluded that any abnormal accumulation of fluid or a mass that develops near the breasts months after breast implants were implanted must be evaluated.

The oncologists also state that even if the BIA-ALCL is confined to the scar capsule that surrounds the implant and even if that capsule is totally removed through proper explant surgery, the patient must be followed for 2 years.  Here is the link to their guidelines: https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf#page17

Although rare, it seems that BIA-ALCL is not “very rare.”  In Australia, which can track medical problems from any kind of implants better than the tracking of implants in the U.S., they estimate that BIA-ALCL affects one woman per 1,000 with breast implants.  The estimates were much lower in the U.S., but there is no reason to think BIA-ALCL is less likely to develop in women in the U.S.  Given the dramatic increase in diagnoses in recent years, it is clear that BIA-ALCL was under-diagnosed and under-reported for many years.

The sooner ALCL is diagnosed, the more likely it can be treated easily and effectively by removing the implants and capsule.  At later stages, treatment includes chemo and is less likely to be successful, as specified by researchers at the well-respected MD Anderson Cancer Center in a medical journal in 2013. Their study followed women for 5 years and found that ALCL related to breast implants sometimes requires chemotherapy, and approximately 25% of the implant patients with the more serious type of ALCL died during the 5 years following their diagnosis.[1] Dr. Anna Mazzucco published a response to this study,[2] urging physicians to respond quickly and to check patients who have swelling near their implants for ALCL. This would require cytology testing rather than testing for bacteria. The authors of the original study also published a response to Dr. Mazzucco’s article, expressing similar concerns.[3]

For more information, see our summary of that study here.

ALCL caused by breast implants can result in swelling, which is often mistaken for an infection and treated with antibiotics. Antibiotics are ineffective against ALCL and the delay in timely and appropriate treatment for ALCL is dangerous.

Unfortunately, some health insurance companies have traditionally not covered the cost of medical tests or treatment for women with breast problems related to cosmetic breast implants. The published articles on ALCL clearly indicate that this can result in undetected cancer of the immune system (ALCL), which can be fatal. In addition, delays in treatment for ALCL can be extremely expensive for patients and their insurance companies; the companies would be required to pay for treatment for ALCL when it is eventually diagnosed at a later stage.

References

  1. Miranda RN, Aladily TN, Prince HM, et al: Breast implant–associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 32:114-120, 2014.
  2. Mazzucco, AE. Next Steps for Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol, 2014.
  3. Miranda RN. Reply to AE Mazzucco. J Clin Oncol, 2014. Early Release publication. June 16, 2014.

Phthalates and Children’s Products

Paul Brown, Keris Krenn Hrubec, Dana Casciotti, PhD, Brandel France de Bravo, MPH, Stephanie Fox-Rawlings, PhD, Cancer Prevention & Treatment Fund

Phthalates are synthetic chemicals found in every home, in plastic toys, personal care products such as shampoos and lotions, vinyl floors, and shower curtains. They are also found in some medical products, such as saline bags, feeding tubes and catheters. They are used to make plastic flexible and to add fragrances to soap and other personal products.  Unfortunately, these chemicals don’t stay inside the products. Based on recent research on ants, scientists have concluded that the high levels of phthalates in the bodies of insects around the world are the result of phthalates in the air.[1] Because phthalates are released into the air and dust around us, they are found in human urine, blood, and breast milk.[2] Levels are highest in women and children ages 6 to 11. Young children may have higher levels of phthalates in their bodies because their hands find their way into their mouths more frequently: they touch objects made with phthalates and surfaces covered with phthalate dust, and then their hands touch their mouths.

Phthalates are called “endocrine disruptors” because they affect the body’s hormones by mimicking them or blocking them. They interfere with the body’s natural levels of estrogen, testosterone, and other hormones, which is why they are called “disruptors.” Endocrine disruptors are hard to study for several reasons: 1) we are exposed to very small quantities from many different sources every day, 2) researchers have proved that, unlike other chemicals, these appear to have more serious effects at lower levels than at higher levels.[3] Usually, we assume that the higher the dose or exposure, the greater the harm, but endocrine disruptors play by different rules. The director of the National Institute of Environmental Health Sciences, Linda Birnbaum, says that chemical manufacturers are asking “old questions” when they test for safety even though “science has moved on.”[4]

Hormones can increase the risk of some cancers, whether those hormones are natural or synthetic. Too much or too little of a hormone can be harmful. Is a child who is exposed to phthalates more likely to develop cancer as an adult?  No one knows for sure but animals exposed to phthalates are more likely to develop liver cancer, kidney cancer, and male reproductive organ damage.[5]

Phthalates are believed to also affect girls’ hormones, but the health impact is not yet known. Studies also show associations between children’s exposure to phthalates and the risk of asthma, allergies and bronchial obstruction.[6][7][8]

Researchers at Mount Sinai also found a link between obesity and phthalates.[9] They found that among overweight girls ages 6 to 8, the higher the concentration of certain phthalates (including low molecular weight phthalates) in their urine, the higher their body mass index (BMI).  BMI takes height and weight into account when determining if someone is overweight. A study among Danish children ages 4 to 9 found that the higher the concentration of phthalates (all of them), the shorter the child. This was true for girls and boys.[10] More research is needed to determine the impact of phthalates on height and BMI.

Even short-term exposure has now been linked to developmental deficits.[11] Researchers found that children in intensive care units were exposed to the phthalate DEHP through plastic tubing and catheters. The children had 18 times (!)  as much DEHP in their blood compared to children who had not spent time in the ICU. Four years later, the children who had been exposed to DEHP had more problems with attention and motor coordination. The researchers found that the DEHP caused these problems regardless of medical complications or treatments.

Prenatal Exposure to Phthalates

Childhood exposure to phthalates begins in the womb. Several studies that have tested phthalate levels in women in their third trimester of pregnancy have found health effects in the infants, toddlers, and older children of the mothers with the highest levels. There are many different types of phthalates. Most studies look at several types, and the effects tend to vary by type.  A 2011 study found that six-month-old boys whose mothers had the highest phthalate levels scored lower on brain and motor development tests.[12] The same effect was not true for female infants.

Research indicates that boys exposed to phthalates while in the womb may be more likely to develop smaller genitals and incomplete descent of the testicles.[13] Boys who are born with undescended testicles are 2-8 times more likely to develop testicular cancer later on than men born with both testicles descended[14] (their risk is lessened if they get corrective surgery before age 13.[15]). Studies by Harvard researchers have shown phthalates may alter human sperm DNA and semen quality.[16][17][18][19]

Columbia University researchers discovered that three-year olds with high prenatal exposure to two types of phthalates were more likely to have motor delays.[20] They also reported that three phthalates were linked to certain behavior problems in three-year olds, such as social withdrawal.  One phthalate in the study was linked to lower mental development in girls.

Other studies have also linked increased prenatal phthalate exposure to behavior problems. Researchers in Taiwan found an association with aggressive and disobedient behaviors in eight-year-olds of both sexes.[21][22] Similarly, researchers from Icahn School of Medicine at Mount Sinai found that higher levels of exposure to phthalates during gestation were associated with aggression, rule-breaking, and conduct problems for males only.[23]

Researchers at Mount Sinai School of Medicine studied the impact of prenatal exposure to “low molecular weight” phthalates—the kind often found in personal care products and the coatings of some medications—on the social behavior of children ages 7 to 9. Children who were exposed to higher levels of these phthalates, which include DEP and DBP, had worse scores for social learning, communication, and awareness.  This means they were less able to interpret social cues, use language to communicate, and engage in social interactions.[24]

What Is Being Done to Limit Children’s Exposure?

As of February, 2009, children’s toys and child care products sold in the U.S (such as teething rings and plastic books) cannot contain certain phthalates.  The ban on those phthalates is the result of a law passed in 2008, the Consumer Product Safety Improvement Act.  The law permanently bans certain kinds of phthalates (BBP, DBP and DEHP) from toys and child care products, and temporarily bans other phthalates (DIDP, DINP and DnOP) until a scientific board (the Chronic Hazard Advisory Panel) determines for the Consumer Product Safety Commission (CPSC) whether or not they are safe. In 2014 the Chronic Hazard Advisory Panel determined that stricter regulations were appropriate.[25] It stated that the permeant bans should remain on BBP, DBP and DEHP, and that DINP should be added to this list. Furthermore, because a large component of exposure to these chemicals comes from food and other products, it recommended increased regulation. The panel was less concerned about DIDP and DnOP, but recommended additional study. Finally, the panel recommended permanently banning DIBP, DPENP, DHEXP, and DCHP, and putting an interim ban on DIOP.

A few months before the 2008 bill passed, major retailers such as Wal-Mart, Target, and Babies “R” Us promised to remove or severely restrict children’s products containing phthalates by the end of 2008.[26] That provided added incentives for major companies making teething rings and other soft plastic products to stop using phthalates.

The ban in the U.S.followed similar bans in other countries.  In 2006, the European Union banned the use of 6 phthalates in toys that may be placed in the mouth by children younger than 3 years old.[27] The banned phthalates are DINP, DEHP, DBP, DIDP, DNOP, and BBzP.  Fourteen other countries, including Japan, Argentina, and Mexico, had also banned phthalates from children’s toys prior to the U.S.

Phthalate Exposure Continues

A 2014 study looking at data over a ten-year period (2001– 2010) found that exposures to some phthalates have declined while others have increased. Americans’ exposure to three substances permanently banned in toys and children’s products—DEHP, DBP and BBP—has declined. But exposure to other phthalates such as DiNP and DiBP, as measured in urine, has increased. The higher  levels of DiBP and other phthalates “suggest that manufacturers may be using them as substitutes for other phthalates even though the US EPA has expressed concern about their use.”[28] It is surprising that DiNP exposure has gone up since it was banned on an interim basis from children’s toys and children’s products.  Additionally, in 2013, California declared DiNP a carcinogen.[29]

Even with the ban on phthalates in children’s toys, children, and adults, too, continue to be exposed because these chemicals are in many products, including food packaging, pharmaceuticals, medical devices and tubing, soap, lotions, and shampoos.[30] Johnson & Johnson recently reformulated its baby shampoo to remove harmful chemicals,[31] and Proctor & Gamble has promised to eliminate the phthalate DEP from fragrances used in its products by the end of 2014.[32] DEP is used in personal care products  and “reductions in DEP exposures have been the most pronounced,” according to the 2014 study.[33] Ten years ago, more than a thousand companies pledged to remove “chemicals of concern from personal care products,” however, it is unclear how many have done so. The U.S. Food and Drug Administration (FDA) regulates many of these products, including baby shampoo and baby lotion.  If the FDA does not decide to ban phthalates from these products, legislation would be required to do so.

The U.S. Environmental Protection Agency (EPA) developed an “action plan” in 2010 for eight phthalates “because of their toxicity and the evidence of pervasive human and environmental exposure.” [34] The phthalates are being studied for health effects and for alternatives. The EPA developed two new rules for these chemicals. However, the rules were delayed and then withdrawn in 2013.[35] In 2014, seven of these phthalates were included in the Toxic Substances Control Act work plan, because of their potential for harm and the frequency of exposure.[36] The eighth phthalate (DnPP) was not included because it is no longer being used in new products. The chemicals on the work plan are to be assessed for additional study or regulation, but it is unclear when that assessment will occur.

While other government agencies are concerned about phthalates in specific products, the EPA’s job is to focus on the chemicals for use in any kind of product and establish safety standards for each phthalate.  A challenge for the EPA is to set safety standards that make sense given that people may be exposed to several phthalates from many different sources. Teenage girls, for instance, have been found to use up to 17 personal care products a day.[37] Setting safety standards for phthalates individually or for individual products without considering their interactions and cumulative effects could underestimate the real-world risks of phthalates to the health of children and adults.

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

References

  1. Rudel RA, Brody JG, Spengler JD, Vallarino J, Geno PW, Sun G, Yau A (2001). Identification of selected hormonally active agents and animal mammary carcinogens in commercial and residential air and dust samples. Journal of Air and Waste Management Association 51(4):499-513.
  2. Kato K, Silva MJ, Reidy JA, Hurtz D, Malek NA, Needham LL, Nakazawa H, Barr DB, Calafat AM (2003). Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxhexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate. Environmental Health Perspectives 112: 327-330.
  3. Vandenberg et al. (2012). Hormones and Endocrine Disrupting Chemicals: Low-dose Effects and Nonmonotonic Dose Responses. Endocrine Reviews.  First published ahead of print March 14, 2012 as doi:10.1210/er.2011-1050.
  4. Cone, Marla and Environmental Health News. Low Doses of Hormone-Like Chemicals May Have Big Effects. Scientific American.march 15, 2012. http://www.scientificamerican.com/article.cfm?id=low-doses-hormone-like-chemicals-may-have-big-effects.
  5. Vastag, B., (2001). CDC Unveils First Report on Toxins in People, JAMA 285(14): 1827-1828.
  6. Jaakkola JJ, Knight TL (2008 July). The Role of exposure to phthalates from polyvinyl chloride products in the development of asthma and allergies: a systematic review and meta-analysis. Environ Health Perspect, 116(7): 845-53.
  7. Kanazawa A, Kishi R (2009 May). Potential risk of indoor semivolatile organic compounds indoors to human health. Nippon Eiseigaku Zasshi, 64(3): 672-82.
  8. Hsu NY, Lee CC, Wang JY, et al. (2012). Predicted risk of childhood allergy, asthma, and reported symptoms using measured phthalate exposure in dust and urine. Indoor Air. 22(3): 189-99.
  9. Teitelbaum SL, Mervish N, L Moshier E, Vangeepuram N, Galvez MP, Calafat AM, Silva MJ, L Brenner B, Wolff MS. (2012, January).Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environmental Research 112:186-193.
  10. Boas M, Frederiksen H, Feldt-Rasmussen U, Skakkebaek NE, Hegedus L, Hilsted L, et al. (2010). Childhood exposure to phthalates: associations with thyroid function, insulin-like growth factor I, and growth. Environmental Health Perspectives 118:1458-1464.
  11. Verstraete S, Vanhorebeek I, Covaci A, Güiza F, Malarvannan G, Jorens PG, Van den Berghe G. (2016). Circulating phthalates during critical illness in children are associated with long-term attention deficit: a study of a development and a validation cohort. Intensive Care Med 42(3):379-92.
  12. Yeni Kim Y, Eun-Hee Ha, Eui-Jung Kim, et al. (2011). Prenatal Exposure to Phthalates and Infant Development at Six Months: Prospective Mothers and Children’s Environmental Health (MOCEH) Study, Environmental Health Perspectives. 119(10): 1495-500.
  13. Main KM, Skakkebaek NE, Virtanen HE, Toppari J (2010). Genital anomalies in boys and the environment. Best Pract Res Clin Endocrinol Metab.Apr;24(2):279-89.
  14. Toppari J, Kaleva M. Maldescendus testis. Horm Res 1999;51:261-9.
  15. Pettersson A et al. (2007) Age at surgery for undescended testis and risk of testicular cancer. New England Journal of Medicine 356:1835-41.
  16. Duty, S. M., M. J. Silva, et al., (2003). Phthalate exposure and human semen parameters. Epidemiology 14(3): 269-77.
  17. Duty, S. M., N. P. Singh, et al., (2003). The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay. Environ Health Perspect 111(9): 1164-9.
  18. Duty, S. M., A. M. Calafat, et al., (2004). The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters. J Androl 25(2): 293-302.
  19. Duty, S. M., A. M. Calafat, et al., (2005). Phthalate exposure and reproductive hormones in adult men. Hum Reprod 20(3): 604-10.
  20. Whyatt RM, Liu X, Rauh, VA, Calafat AM, Just AC, Hoepner L, Diaz D, et al. (2012). Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor and behavioral development at age three years.  Environmental Health Perspectives 120(2):290-5.
  21. Lien YJ, Ku HY, Su PH, Chen SJ, Chen HY, Liao PC, Chen WJ, & Want SL (2015). Prenatal Exposure to Phthalate Esters and Behavioral Syndromes in Children at 8 Years of Age: Taiwan Maternal and Infant Cohort Study. Environ Health Perspect 123(1): 95–100.
  22. Prenatal Phthalate Exposures and Neurobehavioral Development Scores in Boys and Girls at 6–10 Years of Age. Environ Health Perspect 122(5): 521–528.
  23. Kobrosly RW, Evans S, Miodovnik A, Barrett ES, Thurston SW, Calafat AM, & Swan SH (2014).
  24. Miodovnik A, Engel SM, Zhu C, et al. (2011). Endocrine disruptors and childhood social impairment.  Neurotoxicology Mar;32(2):261-7.
  25. CPSC. Chronic Hazard Advisory Panel on Phthalates and Phthalate Alternatives. 2014. http://www.cpsc.gov/PageFiles/169902/CHAP-REPORT-With-Appendices.pdf
  26. Pereira, J. and Stecklow, S. (2008, May). Wal-Mart Raises Bar on Toy-Safety Standards, The Wall Street Journal.
  27. Sathyanarayana S, Swan SH et al., (2008, February). Baby Care Products: Possible Sources of Infant Phthalate Exposure, Pediatrics, Vol. 121, No. 2.
  28. Zota AR, Calafat AM, & Woodruff TJ (Advance on-line publication January 15, 2014) Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001-2010.
  29. Lee SM, (January 15, 2014). Banned chemicals replaced by worrisome ones, UCSF study shows. SFgate.com (San Francisco Chronicle).
  30. U.S. Food and Drug Administration (2008). Phthalates and Cosmetic Products. Retrieved November 4, 2009 at http://www.fda.gov/Cosmetics/ProductandIngredientSafety/SelectedCosmeticIngredients/ucm128250.htm
  31. Thomas K (January 17, 2014). The ‘No More Tears’ Shampoo, Now With No Formaldehyde. The New York Times. http://www.nytimes.com/2014/01/18/business/johnson-johnson-takes-first-step-in-removal-of-questionable-chemicals-from-products.html.
  32. Prcoter & Gamble Web site: What are Phthalates?  Accessed January 22, 2014. http://www.pg.com/en_US/sustainability/safety/ingredients/phthalates.shtml.
  33. Zota AR, Calafat AM, & Woodruff TJ (Advance on-line publication January 15, 2014) Temporal Trends in Phthalate Exposures: Findings from the National Health and Nutrition Examination Survey, 2001-2010.
  34. EPA. Phthalates Action Plan Summary. http://www.epa.gov/assessing-and-managing-chemicals-under-tsca/phthalates.
  35. Sheppard Kate (September 6, 2013). EPA Quietly Withdraws Two Proposed Chemical Safety Rules. Huffington Post. http://www.huffingtonpost.com/2013/09/06/epa-chemical-safety_n_3882262.html.
  36. EPA. TSCA Work Plan for Chemical Assessments: 2014 Update. https://www.epa.gov/sites/production/files/2015-01/documents/tsca_work_plan_chemicals_2014_update-final.pdf
  37. Environmental Working Group. 2008. Sutton R. Adolescent exposures to cosmetic chemicals of concern. http://www.ewg.org/research/teen-girls-body-burden-hormone-altering-cosmetics-chemicals.

Stomach Cancer and Diet: Can Certain Foods Increase Your Risk?

Laura Gottschalk, PhD, Cancer Prevention & Treatment Fund

There is growing evidence that the foods we eat can increase the chances of developing certain types of cancer. A new report by the World Cancer Research Fund International says that stomach cancer is one of them.

Stomach cancer is the fifth most common cancer worldwide and the third most common cause of death from cancer.[1] Older adults are more at risk to develop stomach cancer with most people in the U.S. being diagnosed over the age of 70.[2] Men are twice as likely to develop stomach cancer compared to women.[2]

You can’t control how old you are or whether you are a man or woman, but what you eat can either increase or decrease your chances of developing stomach cancer. The World Cancer Research Fund looked at all the scientific research that was available discussing diet, weight, physical activity, and the risk of stomach cancer.[3] After looking at 89 studies that examined nearly 77,000 cases of stomach cancer, the report concluded that each of the following can increase a person’s risk for developing stomach cancer.

  • Drinking three or more alcoholic drinks per day.
  • Eating foods preserved by salting, such as pickled vegetables and salted or dried fish, as traditionally prepared in East Asia.
  • Eating processed meats that have been preserved by smoking, curing or salting, or by the addition of preservatives. Examples: ham, bacon, pastrami, salami, hot dogs, and some sausages
  • Being overweight or obese, as measured by body mass index (BMI).

Based on their findings, the WCFR has made several recommendations to reduce your risk of stomach cancer:

  • Maintain a healthy weight
  • Be physically active
  • Eat a healthy diet that avoids processed meat and limits salt
  • Limit your alcohol consumption

These recommendations are good ones for preventing cancer in general, not just stomach cancer.

Still not convinced to give up your 6-packs, kimchi, and bacon just yet? This is just the latest of many studies showing that being overweight and eating processed meats increases your risk of cancer. And, previous research has also shown that drinking more alcohol increases your chances of developing cancer.[4] However, this is probably the most comprehensive study showing the link between a range of eating and drinking habits and stomach cancer.

In addition to what you eat, there are other aspects of your life that increase the risk of stomach cancer.

  • Smoking: It is estimated that 11% of stomach cancer cases are due to smoking.
  • Infection: A bacteria called pylori is known to cause chronic inflammation of the stomach which can lead to stomach cancer. Fortunately, food sanitation in developed countries dramatically cuts down on risk of infection.
  • Industrial chemicals: Exposure to dust and high-temperature environments in the workplace increases the risk of stomach cancer.

If you can’t reduce the risks of smoking, infection or industrial chemicals, changing your diet is the best option for reducing your chances of stomach cancer. Eating fresh vegetables and meats is better than preserved and processed ones. That doesn’t mean you should never eat another hot dog or slice of bacon, but it does mean trying to eat them only rarely. As with most things, moderation is key. Try and balance your diet:  don’t just decrease the amount of unhealthy foods you eat, but also increase the amount of healthy foods. Studies have shown that eating lots of fresh fruits and vegetables, especially citrus fruit,[5] may even reduce your chances of developing stomach cancer![3]

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

References

  1. end Centers for Disease Control and Prevention. “Global Cancer Statistics.”  Department of Health and Human Services. 02 Feb. 2015. Accessed: 05/04/2016. http://www.cdc.gov/cancer/international/statistics.htm
  2. end National Cancer Institute. “What you need to know about stomach cancer.” NIH Publication No. 09-1554. Printed September 2009. Brochure.
  3. end World Cancer Research Fund International/American Institute for Cancer Research. Continuous “Update Project Report: Diet, Nutrition, Physical Activity and Stomach Cancer.” 2016. Available at: wcrf.org/stomach-cancer-2016.
  4. end IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. “Personal habits and indoor combustions. Volume 100 E. A review of human carcinogens. Exit Disclaimer.” IARC Monographs on the Evaluation of Carcinogenic Risks in Humans. 2012: 100(Pt E):373-472.
  5. end Bae JM, Lee EJ, et al. “Citrus fruit intake and stomach cancer risk: a quantitative systematic review.” Gastric Cancer. 2008;11(1):23-32.

Phthalates Q&A

By Paul Brown & Stephanie Fox-Rawlings, PhD
Updated 2016

Phthalates are synthetic chemicals found in everyday plastic products, including toys, children’s care products, medical tubes and saline or blood bags, and food packaging. They are used to make plastic flexible.  They are also used in many personal care products that smell good, such as shampoo and creams, as well as air fresheners. The use of some phthalates is being restricted in some products; however, they are still very common. Phthalates can leach out of the plastic to cause health problems, especially for young children.

Q: Animals exposed to phthalates are more likely to develop serious diseases and health problems, such as liver cancer, kidney cancer, and male reproductive organ damage1, but have any studies shown that phthalates cause health problems in humans?

A: Yes, studies by Harvard researchers have shown that phthalates may damage human sperm DNA, reduce sperm numbers, and reduce its mobility2, and another study from several major medical centers has found that phthalates may cause genital changes for boys.3 Mount Sinai researchers found that girls exposed to more phthalates were more likely to be overweight.[end Wolff MS. (2012, January).Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environmental Research 112:186-193] Other studies have shown that being exposed to phthalates increases the chance of developing asthma, allergies and bronchial obstruction.4

Q: Can phthalate exposure affect a child’s behavior?

A: Yes, prenatal exposure to phthalates and/or as a young child increases the chances of cognitive and behavior problems.5 Higher levels of phthalates have been associated with attention and memory problems, increased aggression and law-breaking behaviors, as well as poor social skills.

Q: Have scientists representing the European Union concluded that phthalates are safe?

A: No, in 2006, the European Union banned the use of 6 phthalates in toys that may be placed in the mouth by children younger than 3.6 The banned phthalates are DINP, DEHP, DBP, DIDP, DNOP, and BBzP. More recently the European Union banned the use of DEHP, BBP, DBP and BiBP in electronic equipment starting in 2019. The chemicals cause environmental and health hazards during recycling or disposal.7

Q: How are phthalates regulated in the US?

A: As of February 2009, U.S. law bans children’s toys and child care products related to sleep or feeding that contain the phthalates BBP, DBP, or DEHP. Toys or items that can be placed in a child’s mouth cannot contain DIDP, DINP, or DnOP.8 In 2014, the Chronic Hazard Advisory Panel recommended banning DIBP, DPENP, DHEXP, DCHP, and DIOP.9 The Consumer Protection and Safety Commission (CPSC) followed with a proposed a rule to ban DIBP, DPENP, DHEXP, and DCHP in children’s toys and care products.10 However a final rule (and thus the ban) has not been published. The Environmental Protection Agency (EPA) has planned to assess seven phthalates under the Toxic Substances Control Act, which could limit their use in all kinds of products.11 These are DBP, DIBP, BBP, DEHP, DnOP, DINP, and DIDP. However, it is unclear when assessment will occur.

Q: If phthalates are banned, will the toy industry start using unsafe alternatives?

A:  No, federal legislation requires that alternatives to the banned phthalates are not hazardous under the Federal Hazardous Substance Act.8 Manufactures are also required to sufficiently test their product to insure it will not cause injury through normal use or predictable misuse.

Q: Should the Consumer Product Safety Commission (CPSC) establish federal regulations for phthalates that preempt state laws?

A: That would be a bad idea because some States have better laws than the federal government. The CPSC is a small agency that has a hard time keeping up with reports of unsafe products that are sold in the U.S. In 2015, CPSC recalled more than 600 distinct products, including 52 for children and babies.11 The states of California and Washington have passed strong laws to protect adults and children from unsafe products, and it would be inappropriate for federal laws to interfere. California has listed six phthalates (DBP, DEHP, BBP, DINP, DIDP, and DNHP) on their Prop 65 lists of chemicals known to cause cancer, birth defects or reproductive harm.12 In Washington state, the definition of “children’s product” is broader that that used by the CPSC. Therefore, there are some children’s products that cannot be sold in the state of Washington but are not banned by the CPSC. Examples include children’s cosmetics or clothing that are not packaged as toys.13

For more information, contact Dr. Diana Zuckerman or Paul Brown at (202) 223-4000 or by e-mail at dz@center4research.org and pb@center4research.org

Agent Orange and Serious Diseases including Multiple Myeloma

Nicholas J. Jury, PhD and Diana Zuckerman, PhD
2015

It has taken many years to determine how Agent Orange exposure during the Vietnam War has harmed the health of those who were exposed. One of the reasons is that it can take decades for cancer to develop after a dangerous exposure.  Agent Orange was used extensively by the United States military during the Vietnam War to clear vegetation to make it easier to see enemy soldiers. Agent Orange was contaminated with dioxin, making it more dangerous to humans. Nearly 1.5 million veterans were exposed to Agent Orange during the war 14  when approximately, 20 million gallons of Agent Orange were sprayed over Vietnam during Operation Ranch Hand. 15,16

Although more research is still needed to learn more about the risks of Agent Orange, by 2012, the Institute of Medicine had concluded that individuals exposed to Agent Orange are more likely to develop these types of cancers and serious diseases 17:

Cancers:

  • Chronic B-cell leukemia
  • Chronic lymphocytic leukemia
  • Hodgkin disease
  • Non-Hodgkin lymphoma
  • Prostate cancer
  • Respiratory cancers (bronchus, larynx, lung, and trachea)
  • Soft tissue sarcoma

Serious diseases:

  • Early-onset peripheral neuropathy
  • High blood pressure
  • Ischemic heart disease
  • Parkinson disease
  • Stroke
  • Type 2 diabetes

The report also stated that some of the children being born to those exposed had spinal cord birth defects. 18

New research indicates Agent Orange also increases the chances of developing a type of cancer of the bone marrow called multiple myeloma.

Veterans who have been exposed to Agent Orange or other herbicides during military service are eligible to receive Veterans Administration health care benefits and compensation for respiratory cancers without having to prove the connection between their disease and exposure.  19

Does Agent Orange cause Multiple Myeloma?

Bone marrow is crucial for making new blood cells. Multiple myeloma causes blood cells to accumulate in the bone marrow and interfere with the process of making new blood cells. 20  Patients who develop multiple myeloma are usually diagnosed first with a condition called monoclonal gammopathy of undetermined significance (MGUS). 21, 22  Patients who have MGUS tend to develop multiple myeloma, and this risk increases over time. 23  More than 26,000 people are expected to be diagnosed with multiple myeloma this year, and less than half are predicted to survive. 24

In its 2012 report, the Institute of Medicine stated that there was insufficient evidence to conclude that exposure to Agent Orange can cause multiple myeloma. 25  However, a study published in a cancer journal in 2015 reported that veterans who were exposed to Agent Orange were 2.4 times more likely to develop MGUS than the veterans who were not exposed to it. 26  The study was based on 958 veterans who served in the United States Air Force during Operation Ranch Hand. This study provides compelling evidence that Agent Orange exposure can increase the risk of multiple myeloma.

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.

Endometrial cancer: what you need to know

By Laurén Doamekpor, M.P.H.
December, 2013

What is endometrial cancer?

Endometrial cancer—also called uterine cancer—is the most common cancer affecting a woman’s reproductive system. It is diagnosed when tumors start growing in the lining of the uterus, which is called the endometrium. Studies show that endometrial cancer is much more likely to occur in women who have already reached menopause, and most endometrial cancer is diagnosed around age 70.27 When physicians and medical experts talk about endometrial cancer, they often refer to it as type I or type II. Type I endometrial cancer is more common, and is influenced by levels of the female hormone estrogen in a woman’s body.28 Anything that affects a woman’s estrogen levels can potentially raise or lower a woman’s risk of developing type I endometrial cancer.29 Type II is less common and does not seem to be related to estrogen.30

In 2013, 49,560 new cases of endometrial cancer were diagnosed in the U.S., and about 8,000 women are expected to die from it this year.31

What are common symptoms of endometrial cancer?

Abnormal vaginal bleeding or discharge are frequently reported symptoms, as is pain in the pelvic area, and pain during intercourse.32  However, a woman can have endometrial cancer without having any of these symptoms, and women can have these symptoms without having cancer. You know your body best, so it is important to see your doctor if you experience any symptoms that seem out of the ordinary.

Who is at risk?

Some of the factors that increase a woman’s chances of getting endometrial cancer are out of her control, but she can reduce her risks.  These factors increase a woman’s risks of endometrial cancer:

  • Had her first menstrual period before age 126
  • Has a family history of endometrial cancer6
  • Has or had trouble getting pregnant6
  • Has used or is using tamoxifen, a drug used to treat or prevent some types of breast cancer. Tamoxifen blocks estrogen to the breast, starving cancer cells that like to feed off of estrogen, but it acts like estrogen on the uterus.6
  • Had menopause after age 5533
  • Is obese – Studies suggest that obesity may be the largest risk factor for endometrial cancer.4

The more menstrual cycles a woman has in her life, the greater her risk.  That is why either early menstruation or late menopause (or both) can increase a woman’s risk of getting endometrial cancer.  And that is why taking birth control pills lowers a woman’s risk of endometrial cancer. Oral contraceptives eliminate “real” menstruation, replacing it with “withdrawal bleeding.”34

Screening and diagnosis

For women without symptoms, there are no accepted guidelines for a routine screening test.  That is why it is important to see your doctor if you experience any symptoms. Most women with symptoms that are consistent with endometrial cancer will receive one or more of the following tests, in addition to a physical exam and blood tests:

  • Pelvic exam: A pelvic exam will allow your doctor to check your vagina and uterus for any unusual changes in size or shape.
  • Transvaginal ultrasound: This type of ultrasound (sound waves) makes a picture of the uterus, and can be used to detect small masses.
  • Biopsy: A biopsy involves the removal of tissue from the uterus to test whether cancer cells are present. 35

What are the treatment options?

If you have been diagnosed with endometrial cancer, treatment depends on the type of uterine cancer you have and how far it has spread, your age, and how fast the tumor is likely to grow.36 Treatment usually includes:

  • Surgery to remove the tumors
  • Chemotherapy
  • Radiation therapy
  • Hormone therapy to block hormones and keep them from feeding cancer cells 10

How can you lower your risk of endometrial cancer?

Did you know that being overweight or obese increases your risk of many types of cancer, including endometrial cancer?  Keeping your weight down is the number one way you can reduce your risk, so limit the number of calories you eat and drink and stay (or get) active.  You can read more about the link between excess weight and cancer here. Scientists have proposed a few different explanations for this link, but one of them is that fat tissues secrete hormones, including estrogen. Abnormal amounts of estrogen circulating in the body increase a woman’s chances of developing type I endometrial cancer.

Dropping pounds (or at least not gaining weight) offers many health benefits in addition to lowering your risk of endometrial cancer. Shedding pounds can be a challenge. One of the easier ways is to cut down on sodas and other sweetened drinks that are high in calories with zero nutritional value.  A 2013 study found that women who drank a lot of sugar-sweetened beverages, such as Coke, Pepsi, and other carbonated beverages (such as 7-Up, Sprite), or non-carbonated drinks such as lemonade or Hawaiian Punch, were more likely to develop type I endometrial cancer than women who didn’t drink them, regardless of their body mass index (BMI), how physically active they were, or whether they had a history of diabetes or smoking. The study was based on postmenopausal, mostly white women who participated in the Iowa Women’s Health Study.  We don’t know if the results would be identical for younger women, or women of color, but we do know that these types of sugary beverages are generally harmful because they cause weight gain and do not provide nutrition.37 (Although the drinks are called “sugary,” most are made with corn syrup, not sugar.)

Physical activity is another way to control or reduce your weight and is one of the NRC’s seven recommended ways to maximize your health. Everyone can benefit from regular exercise, because it reduces the risk of heart disease and diabetes and can help you sleep better and improve your mood.38 Simple changes to your daily routine can make a difference. Read here to learn how to begin an exercise routine that works for your schedule.

The bottom line

If you’re having any pain in the pelvic area or experiencing unusual bleeding or discharge, be sure to tell your doctor.  Many of the factors that increase your risk of endometrial cancer are out of your control. What you can control is the number of sugary drinks you consume. You can lower your chances of endometrial cancer and many other cancers by keeping your weight down and staying active.

Flaxseed: What is it and Can it Keep you Healthy?

Carla Bozzolo, Cancer Prevention and Treatment Fund

1024px-Brown_Flax_SeedsSuddenly, everyone is talking about adding flaxseed to your diet.  What is flaxseed and how can eating it make you healthier?

What is Flaxseed?

Flaxseed is the seed of the flax plant and can be eaten as whole seeds, ground into a powder (flaxseed meal), or the oil can be taken in liquid or pill form.[1] There is evidence that it is a great way to incorporate dietary fiber, antioxidants, and omega-3 fatty acids into your diet.

Flaxseed has been shown to lower cholesterol in some people and it may even reduce the risk of breast cancer. People take flaxseed to help with many digestive conditions, including chronic constipation, diarrhea, diverticulitis (inflammation of the lining of the large intestine), irritable bowel syndrome (IBS), ulcerative colitis (sores in the lining of the large intestine), gastritis (inflammation of the lining of the stomach), and enteritis (inflammation of the small intestine). According to the National Institutes of Health (NIH), more study is needed to prove that flaxseed benefits people who have these conditions.[2]

What’s in This Miracle Seed?

Omega-3 essential fatty acids

Flaxseed is the richest source of omega-3 fatty acids,3 which is good for our hearts, brains, and normal growth and development.4 Omega-3 fatty acid can also be found in fish, plants, nuts, and oils made from nuts. No matter how you consume flaxseed—whole, ground or the oil—you will increase your intake of omega-3 fatty acids.

Lignans

Lignans are a type of plant estrogen that may help slow down certain cancers—cancers that depend on hormones to grow. Lignans also work as an antioxidant, which means they protect cells from the damage that comes with aging. Antioxidants—found in berries and many other foods—may help fight certain cancers. Lignans are concentrated in the coat of the seed so when flaxseed is expressed into oil, the anti-cancer and antioxidant benefits of the lignans are lost.

Dietary fiber

Dietary fiber helps regulate the digestive system and can lower bad cholesterol. Dietary fiber in flaxseed is only found in whole and ground flaxseeds, not in flax oil.

Flaxseed and Breast Cancer

For women who have gone through menopause, a small daily serving of flaxseed (just over half a teaspoon) was enough to lower breast cancer risk. While more research is needed, some studies suggest that for younger women who have not yet gone through menopause flaxseed reduces the risk of breast cancer and slows down the progress of certain breast cancers and other cancers that need estrogen to grow. A study published in 2013 found that eating flaxseed decreased a woman’s chance of getting breast cancer by 82%.

Flaxseed and Cholesterol

Flaxseed (but not flax oil) seems to decrease bad cholesterol among people who have relatively high cholesterol. Once again, women who already went through menopause seemed to benefit most: their “bad” cholesterol dropped more than the bad cholesterol of men or younger women. This is important for older women, because bad cholesterol tends to increase after menopause, as estrogen levels decline.

Who Benefits the Most?

Flaxseed has the potential to benefit everyone as a great source of dietary fiber with almost no side effects.  People with high levels of bad cholesterol and women who are post-menopausal benefit the most.

Different Ways to Eat It

Flaxseed is sold as whole seeds, ground seeds (flaxseed meal), liquid oil, and oil in a pill form. It can easily be added to cereal, baked goods, salad, yogurt, and many other types of food.  Since whole seeds tend to go through the body undigested, ground seeds are considered to be more beneficial.  Flaxseed oil delivers essential fatty acids but it doesn’t have fiber or lignans. If you want to get all the benefits of flaxseed—omega-3 fatty acids, fiber, anti-oxidant and cancer-fighting properties—choose ground flaxseed.  

Cautions

Few side effects have been reported from flaxseed. When taken to reduce constipation, it should be taken with plenty of water.

The fiber in the flaxseed may also lower the body’s ability to absorb medications that are taken by mouth, so it should not be taken at the same time of day that you take pills or dietary supplements.

The Bottom Line

Flaxseeds are a great source of dietary fiber and omega-3 essential fatty acids for men and women of all ages. They don’t have any known serious side effects, and ground flaxseeds are easy to include in the foods you eat every day.

References:

  1. National Institutes of Health. National Center for Complimentary Medicine. Herbs At A Glance: Flaxseed and Flaxseed Oil. April 2012: http://nccam.nih.gov/health/flaxseed/ataglance.htm
  2. National Institutes of Health. National Library of Medicine. Flaxseed: MedlinePlus Supplements. August 2011. http://www.nlm.nih.gov/medlineplus/druginfo/natural/991.html
  3. National Institutes of Health. National Cancer Institute. Antioxidants and Cancer Prevention: Fact Sheet. July 2004. href=”http://www.cancer.gov/cancertopics/factsheet/prevention/antioxidants”>http://www.cancer.gov/cancertopics/factsheet/prevention/antioxidants  
  4. Brown L, Rosner B, Willett W, and Sacks F. Cholesterol-lowering effects of dietary fiber: a meta-analysis. American Journal of Clinical Nutrition. 1999; 69:30-42.  
  5. Cotterchio M, Boucher BA, Kreiger N, Mills CA, & Thompson LU. Dietary phytoestrogen intake–lignans and isoflavones–and breast cancer risk (Canada). Cancer Causes Control.2008; 19:259–272  
  6. Buck K, Zaineddin AK, Vrieling A, Linseisen J, & Chang-Claude J. Meta-analyses of lignans and enterolignans in relation to breast cancer risk. American Journal of Clinical Nutrition. 2010; 92:141–15  
  7. Velentzis LS, Cantwell MM, Cardwell C, Keshtgar MR, Leathem AJ, & Woodside JV.Lignans and breast cancer risk in pre and post-menopausal women: meta-analyses of observational studies. British Journal of Cancer. 2009; 100:1492–1498  
  8. Lowcock E, Cotterchio M, & Boucher B. Consumption of flaxseed, a rich source of lignans, is associated with reduced breast cancer risk. Cancer Causes Control. 2013. E-publicaton ahead of print. Retrieved from href=”http://www.ncbi.nlm.nih.gov/pubmed/23354422″>http://www.ncbi.nlm.nih.gov/pubmed/23354422.  
  9. Pan A, Yu D, Demark-Wahnefried W, Franco O, and Lin X. Meta-analysis of the effects of flaxseed interventions on blood lipids. American Journal of Clinical Nutrition. 2009; 90:288-297.  
  10. Fukami K, Koike K, Hirota K, Yoshikawa H, and Miyake A. Perimenopausal changes in serum lipids and lipoproteins: a 7-year longitudinal study. Maturitas. 1995; 22:193-197.  

 

Testimony of Dr. Jennifer Yttri at FDA Advisory Committee on Tivozanib

May 2013

I am Dr. Jennifer Yttri and I am speaking on behalf of the Cancer Prevention and Treatment Fund of the National Research Center for Women & Families. Our non-profit research center scrutinizes medical data, evaluating scientific evidence of benefits and risks for patients.  We analyze and review research and provide objective and understandable health information to patients, health care providers, and policy makers.  Our organization does not accept funding from pharmaceutical companies and therefore I have no conflict of interest.

Today’s fundamental question is whether the one completed Phase 3 clinical trial is enough to approve the new drug tivozanib as a treatment for patients with renal cell carcinoma.

FDA guidelines recommend two trials that support efficacy of a drug. In some cases, FDA will approve a new drug based on only one trial if that trial shows a significant improvement over existing therapy. In the FDA’s own words: “A conclusion based on two persuasive studies will always be more secure than a conclusion based on a single, comparably persuasive study. Reliance on only a single study will generally be limited to situations in which a trial has demonstrated a clinically meaningful effect on mortality, irreversible morbidity… and [when] confirmation of the result in a second trial would be practically or ethically impossible.”

The NDA submitted for tivozanib relies on one phase 3 study comparing tivozanib to sorafenib. While tivozanib was shown to increase progression free survival by 3 months in patients with renal cell carcinoma, it did not improve overall survival. In fact, there was a non-significant lower overall survival for tivozanib, suggesting the drug may actually harm patients more than it helps them. This one study alone is not enough to meet the FDA’s guidelines for drug approval.

In addition, the study results have inconsistencies that raise red flags about the research and about the drug itself.

1.       Patients receiving tivozanib had increased progression free survival, so why were they more likely to die in the first 30 days due to disease progression, compared to sorafenib. This does not make sense. The deaths in the first 30 days could be due to chance, but the disease free survival could also be due to chance.  More research is needed to clarify the risks as well as the long-term benefits.

2.       FDA noted that 70% of sorafenib patients stopped taking the drug at least temporarily and 44% ended up with a reduced dose. This is much higher than other studies – for example one study highlighted by the FDA had only 14% interruption and 10% reduction.  There is no logical explanation for this, but these unusual problems could make sorafenib seem inferior to tivozanib, when in fact it might be superior.

These inconsistencies may be due to chance or to irregularities in how the studies were conducted in other countries.  Standard of care and assessment of disease varies in the US and other countries, and fewer than 10% of patients enrolled in the trial were in the US.  We agree with the FDA reviewer that it is preferable to enroll US patients, so that the study reflects the disease burden and treatment in the US and can provide better insight into treatment outcomes for US patients.

Regardless of the reason for the inconsistencies in the study, a second, independent, phase 3 study would help determine the safety and efficacy of this drug for treatment of renal cancer.

We urge you to recommend that the FDA require the sponsor to complete a second trial to confirm the positive effect of tivozanib on PFS; address the concern over lower OS; and provide better information on how generalizable the results are in the US population. Based on the data provided, there are no ethical concerns with requiring another trial. With the additional information, the FDA can make an informed decision as to whether tivozanib meets their standards of safety and efficacy.  That is not possible based on this one study with such inconsistent results.