Category Archives: New Cancer Research

Startling link between pregnant mother’s exposure to DDT and daughter’s risk of breast cancer

by Ariana Eunjung Cha, Washington Post
June 17, 2015

Banned by the United States in 1972, the insecticide DDT is best known as the impetus for the modern environmental movement. Since Rachel Carson’s bestseller “Silent Spring” sounded the alarm about the poisonous effects of the chemical on wildlife, the environment and human health, numerous studies have linked it to birth defects, miscarriage and reduced fertility.

Its role in cancer has been less clear. The Environmental Protection Agency classifies DDT as a “probable” carcinogen. Roughly three dozen studies have been published about DDT and breast cancer risk for women who lived during its peak use in the 1950s, but a 2014 meta-analysis of that research found that there was no significant association between exposure and breast cancer risk.

They may have been looking at the wrong generation of women.

A new study published Tuesday in the Journal of Clinical Endocrinology and Metabolism found a startling link between pregnant women exposed to DDT and the breast cancer risk to their daughters.

The study tracked the daughters of women who were part of a study at the Kaiser Foundation Health Plan from 1959 to 1967 near the city of Oakland, Calif. During that time DDT was widely used and accumulated in the fat of animals that we eat and was found in milk, butter, cheese and other products in the food supply. It was also in a number of consumer products, including some wallpaper.

During that period the participants gave birth to 9,300 daughters. Every mother had some measurable level of DDT in her blood. Researchers determined the level of exposure to DDT in utero by analyzing stored blood samples that were taken from the mothers during pregnancy or shortly after they delivered their babies. By using state records and surveying the daughters, who are now in their late 40s and early 50s, they were able to figure out which ones developed breast cancer.

The researchers found that elevated levels of DDT in the mother’s blood were associated with almost a four-fold increase in her daughter’s risk of breast cancer and that this was independent of the mother’s history of breast cancer. They also determined that those with higher levels of exposure were diagnosed with more advanced breast cancer.

About 83 percent of those who got breast cancer had estrogen-receptor positive breast cancer and were more likely to develop HER2-positive breast cancer in which a genetic mutation produces an excess of a protein. In previous studies, DDT has been found to interfere with the function of estrogen and, separately, to activate the HER2 protein, which may explain the link.

Barbara A. Cohn, one of the study’s authors and the director of Child Health and Development Studies at the Public Health Institute in Berkeley, Calif., said the 54-year study is “the first to provide direct evidence that chemical exposures for pregnant women may have lifelong consequences for their daughters’ breast cancer risk.”

Elizabeth Ward, senior vice president of intramural research for the American Cancer Society, said the group of mothers and daughters the researchers are studying is a “unique resource” for studying potential associations between maternal blood levels of chemicals and risk to their children.

“What makes this study interesting is its analysis of in-utero exposure,” she said. However, she said that the number of breast cancer cases was small — 103 — so “the results should be interpreted cautiously.”

In an interview, Cohn said the paper is part of a series of studies on chemicals and their effects on hormones or  development during gestation. Earlier studies she led have looked at the effects of DDT on the time of pregnancy of the daughters of women exposed (they found it could slow their ability to become pregnant or shorten it depending on level of exposure) and on incidence of testicular cancer among the male children (those exposed to the highest levels had an almost three-fold risk  compared with those with lower exposure). She is also studying the effect of other chemicals used for stain control on carpeting and waterproofing for food containers.

“We are looking at a vulnerable period in utero,” she said. “In some ways it is not surprising that early in life is a time when some of these chemicals can have a strong effect.”

Earlier work by Cohn also supports the idea that timing of the exposure matters. In a 2007 paper, she found that DDT affected breast cancer only for women who were exposed before age 14.  The meta-analysis that didn’t find any association between DDT and exposure looked at studies of women who were exposed later in life.

DDT is still widely used in other parts of the world, including regions of Africa and Asia, where it is used to control the spread of malaria.

“Our findings don’t change the perception of benefits, but they do change the perception of risks,” Cohn said. “We are hoping that policymakers will use this information as they continue to debate the use of DDT around the world.”


See original article here.

Public Health Implications of Differences in US and European Union Regulatory Policies for Breast Implants

Diana Zuckerman, PhD, Nyedra Booker, PharmD, MPH, and Sonia Nagda, MD, MPH

Published in Reproductive Health Matters, December 2012

Tens of thousands of defective silicone breast implants were recalled in Europe in 2011–12 soon after the FDA’s unrelated announcement that a rare cancer of the immune system was associated with all saline and silicone gel breast implants. These developments raised questions about whether U.S. and European regulations were protecting patients from unsafe medical implants.

In the US, breast implants are regulated as high-risk medical devices that must be proven reasonably safe and effective in clinical trials and subject to government inspection before they can be sold. In contrast, clinical trials and inspections have not been required for breast implants or other implanted devices in Europe. As a result of these differing standards, the PIP breast implants that were recalled across Europe had been removed from the market years earlier in the US. Nevertheless, the FDA track record on breast implants indicates that studies have provided limited information about safety.

The authors conclude that neither the European Union nor the US has used their regulatory authority to ensure the long-term safety of breast implants. However, in 2012 the EU announced regulatory changes that could improve that situation.

To see the official summary:

Cancer Researchers with Industry Ties Report “Rosier” Results

Stephanie Portes-Antoine and Brandel France de Bravo, MPH, Cancer Prevention and Treatment Fund

With all of the cancer studies being performed today, how can consumers be sure of their accuracy? A study by Dr. Reshma Jagsi at the University of Michigan and her colleagues indicates that cancer studies are more likely to have positive results when the researchers have ties to the company that makes the product being studied.[1]

This study focused on cancer research articles published in eight medical journals, including Cancer, the Journal of the National Cancer Institute, the New England Journal of Medicine, the Journal of the American Medical Association, and the Lancet. An author was categorized as having a conflict of interest if he or she reported one or was employed, at the time of publication, by the company that makes the medical product being studied, or if a drug or medical device manufacturer was a source of funding for the study. Dr. Jagsi and colleagues relied exclusively on disclosures and information given in the articles themselves. They did no further investigation into authors’ financial ties to industry such as checking board memberships or employee listings. For this reason, the authors believe that their findings may underestimate the extent and effects of conflicts of interest in cancer research.

The authors reviewed 1,534 articles on cancer studies published in 2006. Twelve percent of the articles included at least one author employed by industry—a company that makes medical products—and 17% of articles declared industry funding. The articles most likely to have conflicts of interest included those with authors from medical oncology departments; articles from North America; and articles where the first or last author was a man (these are most likely to be the senior author or principle investigator).  Studies having to do with diagnostic radiology were least likely to have conflicts, whereas those involving prostate, lung, skin, and hematologic (blood-related) cancer were most likely to have conflicts.

Nearly one-quarter of the articles disclosed a conflict of interest. By looking at funding sources and author affiliations, Dr. Jagsi and colleagues concluded that 29% of articles had an apparent conflict of interest, meaning that disclosures do not tell the whole story. This discrepancy can be due to many factors: some journals may have chosen to omit certain information in the disclosures; different journals have different guidelines and policies on disclosure; and cultural norms regarding disclosure vary from one region of the world to another.


Cancer studies with conflict
Industry funding of study
Industry employee
Industry funding of other research by author
Lecture fees
Corporate board
Industry-supplied drugs or technology
Testimony/legal team

Source: “Frequency, Nature, Effects, and Correlates of Conflicts of Interest in Published Clinical Cancer Research,” Cancer. 2009; 115:2783-2791. Table in this form reproduced from:

Industry-funded studies were far more likely to focus on treatment than non-industry funded studies (62% vs. 36%) and much less likely to look at epidemiology, risk factors, and effective means of disease prevention and diagnosis (20% vs. 47%).

Randomized clinical trials were more likely to find that a treatment or intervention improved patient survival if a conflict of interest was present. Dr. Jagsi and his co-authors suggest that several factors may account for this. Industry-funded research may tend to design studies that are likely to show their products are effective. The example they give is trials where a drug is tested against a placebo rather than against a drug already in use. Also, journals may be more interested in publishing positive results, which would inadvertently favor studies whose authors have conflicts of interest.

Since randomized clinical trials are the gold standard for the adoption of new therapies and technologies, these conflicts of interest or “funder effects” have serious implications for cancer treatment and public health. Even if industry funding does not lead researchers to exaggerate a treatment or product’s benefits, studies have indicated that they may tend to not publish negative findings. For example, an analysis of 44 studies on the cost-effectiveness of new oncology drugs found that those sponsored by industry were less likely to conclude that a drug was not cost-effective than studies funded by agencies or institutions without a profit incentive, such as government or university-funded studies.[2] In fact, the industry-funded studies were eight times less likely to assess a drug unfavorably than non-industry studies.

Studies dating back as far as 1986 have shown that clinical trials funded by industry are far more likely to favor new therapies over traditional ones.[3] New therapies usually cost more, and usually less is known about their potential risks.

Medical researchers often rely on industry funding, and this is true for cancer researchers. In a study published in 2013, Dr. Francisco Emilio Vera-Badillo and colleagues at the University of Toronto found that 63% of the breast cancer studies they looked at were funded by industry, but they did not find that the results of the studies necessarily favored the companies that paid for them.[4] Other studies, however, indicate that industry funding affects not only the way results are reported but the type of research that is carried out. This is why it is important that medical research—which is for the benefit of all, not just those who manufacture drugs and other therapies—receive funding from diverse sources, including those without a profit incentive. Since the new research indicates that not all conflicts of interest are acknowledged in medical publications, journals should implement stricter policies regarding accurate disclosure of potential conflicts of interest. In addition, peer reviewers and editors should scrutinize the study design and data analyses carefully and ask tough questions of authors to ensure the accuracy of the findings and conclusions. These efforts are especially crucial when the studies involve treatment for potentially fatal diseases such as cancer.

For information on the misrepresentation of effectiveness and side effects of cancer treatments, click here.


  1. Jagsi R, Sheets N, Jankovic A, Motomura AR, Amarnath S, Ubel PA. Frequency, nature, effects, and correlates of conflict of interest in published clinical cancer research. Cancer. 2009;115: 2783-2791.
  2. Friedberg M, Saffran B, Stinson TJ, Nelson W, Bennett CL.. Evaluation of conflict of interest in economic analyses of new drugs used in oncology. Journal of the American Medical Association. 1999; 282: 1453-1457
  3. Davidson RA. Source of funding and outcome of clinical trials. Journal of General Internal Medicine. 1986; 1:155-158.
  4. Vera-Badillo, FE, Shapiro, R, Ocana, A, Amir, E, Tannock, IF. Bias in reporting of endpoints of efficacy and toxicity in randomized, clinical trials for women with breast cancer. Annals of Oncology. 2013; 00: 1-6.

Decisions in the dark: The FDA, breast cancer survivors, and silicone implants

Decisions in the Dark: The FDA, Breast Cancer Survivors, and Silicone Implants warns that industry-funded data indicates that reconstructive surgery patients experience substantially more complications, ruptures and a greater need for additional corrective surgeries than women who receive implants for augmentation purposes. The report also highlights FDA research showing that silicone implants interfere with mammography and may limit future breast cancer treatment options such as lumpectomy and sentinel node biopsy.

The report reveals that:

  • After selling silicone breast implants to tens of thousands of mastectomy patients in the last 5 years, under the conditions that they participate in clinical trials, implant manufacturer Implant included only 80 mastectomy patients in their longitudinal safety study submitted to the FDA, and Mentor Corporation included 0 breast cancer patients in their only long-term study;
  • Industry-funded research reveals that reconstruction patients experience two to three times as many complications and additional surgeries as augmentation patients;
  • Most ruptures (86 percent) are “silent” and can only be detected with MRIs, yet Inamed included less than 30 women in their sample of breast cancer patients undergoing MRIs to determine rupture rates, and the medical societies for plastic surgeons do not advise women to undergo MRIs.
  • Research consistently indicates that reconstruction patients are not enjoying life more than mastectomy patients without reconstruction, and there is evidence they may be more likely to commit suicide; and
  • Breast implants can limit treatment options for later breast cancer.

View report

Reconstructive Breast Implantation After Mastectomy

Diana Zuckerman, PhD, Archives of Surgery: July 2006

Henriksen et al provided useful data on the short-term complications of breast reconstruction with implants.[1] Although the invited critique described the complication rate as “alarmingly high and arguably unacceptable,” the complication rate is even higher in other studies with superior study designs.

For example, a study conducted by implant manufacturer Inamed found that 46% of reconstruction patients needed additional surgery within the first 2 to 3 years after getting silicone gel breast implants 2 – more than twice as high as the 21% reported by Henriksen et al. One explanation is that the women in the Henriksen study had breast implants for an average of only 23 months, compared to 2-3 years in the Inamed study. Henriksen et al reported that 31% developed at least one serious complication and 16% developed at least 2 serious complications. The Inamed study reported that 25% underwent implant removal, 16% experienced Baker III-IV capsular contracture, 6% experienced necrosis, 6% had breast pain, and 6% had scarring, in addition to infections and other complications. [2]

Henriksen et al concluded that “reconstruction failure (loss of implant) is rare.” However, in addition to the short follow-up, Henriksen et al did not use Magnetic Resonance Imaging (MRIs) to detect rupture, thus undercounting the number of ruptures according to the FDA. [3] A study using MRIs found that 20% of reconstruction patients had ruptured implants by the third year;4 very few ruptures were detected without MRIs. Food and Drug Administration scientists concluded that the risk of rupture would likely increase exponentially every year.

Henriksen et al’s lack of MRI use also helps explain the lower rate of additional surgery. If a woman underwent an MRI and learned that her implant was ruptured, she would probably have surgery to remove it.

In his critique, Singh states that “the immunologic and systemic complications ascribed to implants (silicone or saline) have been debunked by the Institute of Medicine’s 1999 definitive report.” However, most research on diseases among implant patients was published after 1999. The IOM report included only 17 studies of autoimmune diseases among implants, almost all of which studied small numbers of women for short periods of time. Many of the studies reported higher levels of disease or symptoms among women with breast implants, which would have reached statistical significance if maintained in larger studies conducted for a longer period of time. For example, the study by Schusterman et al, included only 250 women with implants, all of whom had implants for 2 years.

In 2001, Food and Drug Administration scientists reported a significant increase in fibromyalgia and several other autoimmune diseases among women whose silicone gel breast implants were leaking, compared to women with silicone implants without extracapsular leakage. [3] The National Cancer Institute (NCI) found a doubling of deaths from brain cancer, lung cancer, and suicides among women with breast implants compared to other plastic surgery patients. [5] National Cancer Institute findings regarding autoimmune diseases were not definitive. [6] National Cancer Institute scientists concluded that more research was needed to determine if implants increase the risk of cancer or autoimmune diseases. [5,6]

The unanswered questions about diseases and the high complication rate for breast cancer patients raise important safety issues about breast implants. It is difficult for patients to receive informed consent when definitive long-term data are not yet available.


  1. Henriksen TF, Fryzek JP, Holmich LR et al Reconstructive breast implantation after mastectomy for breast cancer: clinical outcomes in a nationwide prospective cohort study. Arch Surg. 2005; 140: 1152-1159.
  2. Inamed Corporation’s McGhan Silicone-Filled Breast Implants, October 14-15, 2003, slides presented by the FDA,
  3. Brown SL, Pennello G, Berg WA, et al. Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women. Journal of Rheumatology. 2001; 28:996-1003.
  4. FDA Summary Memorandum, Inamed PMA Review Team, March 2, 2005.,
  5. Brinton LA, Lubin, JH, Murray MC, et al. Mortality among augmentation mammoplasty patients: an update. Epidemiology. 2006; 17: 162-169.
  6. Brinton, LA, Buckley, LM, Dvorkina, O et al. Risks of connective tissue disorders among breast implant patients. American Journal of Epidemiology. 2004, 180: 619-627.

FDA Advisory Committees: Does Approval Mean Safety?

Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund

Executive Summary

The U.S. Food and Drug Administration (FDA) has the responsibility to determine if newly developed medical products are safe and effective. Whether it is a prescription medication, a medication sold over the counter, a medical device, a vaccine, or another type of biologic, the product can be marketed for general sale in the United States only if it has FDA approval.

FDA advisory committees are the most visible part of the FDA approval process. They meet in public to review the most controversial and cutting-edge medical products, examining applications for FDA approval. Committee members discuss the strengths and weaknesses of the studies and their enthusiasm or concerns about the medical product under review. At recent FDA advisory committee meetings on controversial drugs and medical devices such as Vioxx®, silicone implants, and antidepressants, the media have provided the Congress and the general public with a glimpse of the approval process.

Questions have arisen about committee members’ financial ties to the companies submitting applications, their commitment to scientific scrutiny, the independence and objectivity of the deliberative process, and inconsistencies between the panel members’ expressed concerns and their approval recommendations.

This report describes the results of a study conducted by the National Research Center (NRC) for Women & Families, providing the first objective analysis of the key role of FDA advisory committees as part of the FDA approval process. The purpose of this report is to better understand the strengths and weaknesses of the FDA’s advisory committee process for FDA’s two largest centers, the Center for Drug Evaluation and Research (CDER) and the Center for Devices and Radiological Health (CDRH).

The study analyzes the voting patterns and committee discussions of a random sample of 6 of 16 drug advisory committees and 5 of 18 medical device advisory panels:

Drug Committees

Antiviral Drugs
Arthritis Drugs
Dermatologic and Ophthalmic Drugs
Gastrointestinal Drugs
Pulmonary and Allergy Drugs
Reproductive Health Drugs

Medical Device Panels
Immunology Devices
Microbiology Devices
Obstetrics and Gynecology Devices
Ophthalmic Devices
Radiological Devices

Data for these advisory committees were collected from the FDA Web site, based on transcripts of advisory committee meetings from January 1998 through December 2005. In that time, the 11 randomly selected advisory committees considered 89 prescription drugs and medical devices, including arthritis medications, LASIK devices, erectile dysfunction drugs, and devices to improve the accuracy of mammograms. There were 866 committee member votes.


As described by FDA officials, its advisory committees meet only to discuss the most controversial or innovative products, or products whose data are not clear-cut. The public might expect, therefore, that many of the drugs and devices reviewed by advisory committees would not be recommended for approval. The data indicate that this is true for some advisory committees, but not others. Overall, the 11 randomly selected advisory committees recommended approval for 79% of the 89 products reviewed between 1998 and 2005. The device advisory panels were even more likely to vote for approval than the drug advisory committees, recommending approval 82% of the time compared to 76% for drugs.

Despite the controversies surrounding many of these products, the votes for or against approval were rarely close. On the contrary, committee members agreed unanimously for 66% of the drugs and 75% of the medical devices that they recommended for approval.

Drug and Device Approval Recommendations

A review of the meeting transcripts indicates that advisory committee members frequently expressed strong concerns about the safety or the efficacy of the drug or device under review. However, those concerns were not necessarily reflected in their recommendations for approval.

There were many examples of committee members who strongly criticized the studies or the medical products under review, and then recommended approval anyway. FDA officials at the meetings almost never expressed concerns about the disconnect between the committee members’ explicitly expressed doubts about safety and effectiveness and their votes in favor of approval.

Of the 50 drug committee voting sessions in the study, 38 (76%) recommended approval of the drug. Most of the votes were unanimous, and almost all (93%) of those unanimous votes recommended approval.

Some of the committees were much more likely to recommend approval than others. The percentage of drugs they recommended for approval ranged from 50% for reproductive health drugs to 100% for arthritis drugs. The percentage of individual votes cast to recommend approval ranged from 50% for reproductive drugs to 98% for arthritis drugs.

What happens after the meetings are over? Of the 38 drugs recommended for approval by the drug advisory committees, all were subsequently approved by the FDA except one drug whose application was withdrawn before FDA made its decision. The FDA also approved four (36%) of the 11 drugs that the drug advisory committees voted against, including products that were opposed by almost all the committee members.

Of the 39 device panel voting sessions studied, 32 (82%) recommended approval of the device. Most of the votes were unanimous, with almost all (92%) of those unanimous votes recommending approval.

The percentage of devices that were recommended for approval ranged from 67% for microbiology devices to 88% for ophthalmic devices. The number of panel member votes cast to recommend approval ranged from 57% for microbiology devices to 91% for radiological devices. Three of the five randomly selected devices panels – the Radiological Devices Panel, the Immunology Devices Panel, and the Microbiology Devices Panel – had unanimous support for approval whenever they recommended approval during the eight years of the study.

Almost all (94%) the devices recommended for approval were subsequently approved by the FDA, and close to half (43%) of the devices that were not recommended for approval obtained FDA approval anyway.

Overall, the study found:

  • Many advisory committees recommend approval for almost every product they review, usually unanimously;
  • Individual committee members can have a disproportionate influence on approval recommendations;
  • Voting patterns differ for drugs and devices, but not when we compare committee members with clinical, scientific, and consumer perspectives;
  • Committee members describe pressure to conform and to recommend approval, and they candidly admit that their votes for approval may not be consistent with their concerns about safety and effectiveness;
  • FDA officials passively acquiesce when they do not respond to committee members’ statements indicating that votes recommending approval are not necessarily based on scientific evidence of safety and effectiveness; and
  • The FDA almost always approves products recommended for approval but also often approves products that advisory committees reject.

Implications and Conclusions

The findings suggest that when the FDA schedules meetings for several of its advisory committees, the outcome is almost certainly going to be FDA approval for the products under review. In most cases the advisory committee will recommend approval, but even products that are not recommended for approval are frequently approved by the FDA. Even lopsided votes against approval apparently do not have much weight, since the FDA subsequently approved many of those products.

Although FDA officials describe the advisory committees as providing diverse perspectives and expertise, the large number of unanimous or nearly unanimous votes suggests that either the data are exceptionally convincing or that the committee members are reluctant to disagree with their colleagues or believe that the FDA wants the advisory committee members to come to consensus.

By combining information from the NRC study with studies of conflicts of interest on FDA advisory committees, it is possible to understand how a few committee members with conflicts of interest can have a disproportionate impact on approval recommendations. NRC’s analysis of meeting transcripts indicates that many committee members’ votes seem inconsistent with their concerns about the safety or efficacy of the drug or medical device under review. These transcripts clearly illustrate the pressures that committee members describe to conform to their colleagues or to be able to vote ‘yes’ even if it means changing the wording of the question so that they can do so in good conscience. The report includes examples of committee members directly trying to influence the views or votes of other committee members.

If the FDA is relying on advisory committees to help determine the conditions of approval, one would expect that FDA officials would provide explicit oral instructions about the types of conditions that the FDA is willing to impose, and that the FDA would impose most of the conditions and then enforce them. That is not the case, however.

Committee members frequently recommended unenforceable or vaguely worded conditions of approval and expressed their intention to recommend approval for products that they did not believe were proven safe or effective. Their candor suggests that they would welcome guidance from the FDA officials present, to make sure their recommendations were appropriate. Nevertheless, during committee discussions FDA officials showed remarkably little interest in providing oral guidance regarding the criteria for approval, or the realities of approval conditions to advisory committee members during the eight years of the study. Conditions of approval imposed by the FDA often did not reflect the conditions recommended by the advisory committees. Conditions that were imposed were rarely enforced.

Overall, the findings indicate that committee members, intentionally or unintentionally, move toward a consensus that often seems inconsistent with their differing views or perspectives in making decisions that may have life-or-death consequences for millions of Americans. Voting for approval contingent upon conditions is a popular compromise, but the FDA does not impose most of the specified conditions on the companies when it grants approval. The Committees’ tendency toward approval seems to reflect the FDA’s goals; in fact, the FDA appears to be even more geared toward approval than the advisory committees. The FDA approved almost all the prescription drugs and devices recommended by the advisory committee, and also frequently approved products that were opposed by the committee members.

Whatever the reasons, many of today’s FDA drug and device advisory committees are rubber stamps for approval almost every time they meet. Moreover, even when an overwhelming majority recommend “nonapproval,” there is a good chance that FDA officials will approve the product anyway. Approval is even more likely for medical devices than it is for drugs.


If the FDA wants to restore confidence in the FDA, and restore the independence that FDA advisory committees were intended to provide, it is essential that the FDA make changes in the policies and process governing its advisory committees. The following recommendations are based on the assumption that the Congress and the FDA are committed to that end:

1. The FDA should stop granting conflict-of-interest waivers for committee members, except under very restricted conditions.

2. The FDA should provide explicit and specific oral guidance whenever needed during advisory committee meetings regarding appropriate criteria for safety and effectiveness, and appropriate criteria for conditions of approval.

3. The FDA should demand more from advisory committee members, and then be more responsive to their concerns.
For a PDF copy of the 50-page report, click here.