Sunday, May 19, 2013

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Considering BPA: State of the Art or Willful Ignorance?

By William H. Goodson III, MD, and Shanaz H. Dairkee, PhD

 The Food and Drug Administration said Friday that it lacks scientific information to ban the chemical bisphenol A from food containers.” —Wall Street Journal, March 31, 2012

 “ ...FDA supports reasonable steps to reduce exposure of infants to BPA in the food supply… FDA will support changes in food can linings and manufacturing to replace BPA to minimize BPA levels….” —U.S. Food and Drug Administration website, March 30, 2012.

William H. Goodson III, MDWhile it is technically correct that the FDA did not ban bisphenol A (BPA), the Wall Street Journal misled readers when it ignored the clear FDA statements that we need to reduce BPA exposure of our most vulnerable citizens. This is a prototype example of the spin-versus-spin arguments that characterize most of the environmental chemical debate. These arguments are not about truth. They are about control of public perception. It is time for willful efforts to skip the spin, outline the challenges, and answer the questions that affect the safety of our children and grandchildren.

The BPA debate centers around three types of data:

  1. BPA promotes breast cancer in animals. Animals exposed to BPA, either in utero or through nursing from dams fed BPA, develop breast epithelial abnormalities and are more susceptible to breast cancer induction by the carcinogen dimethylbenzanthracene (DMBA). Like natural estrogen, BPA stimulates growth of human breast cancer cells transplanted into mice. This is not unexpected, because BPA has been known since the 1930s to act as an estrogen. Note: The concern is not that BPA by itself causes cancer but rather that, through excessive estrogenic stimulation, it promotes cancer. The debate centers on the relation of animal doses to human exposure.

  2. In cell culture studies, BPA causes nonmalignant human breast epithelial cells (obtained by fine needle aspiration from women volunteers) to grow faster and evade apoptosis (programmed cell death), a necessary step for radiation and drugs to kill tumor cells. These changes are referred to as hallmarks of cancer because they are prerequisites for cancer to occur. BPA by itself is sufficient to induce these abnormalities. It is especially relevant that they occur in nonmalignant cells, because these are the target cells that must undergo the required changes for breast cancer to occur. These changes occur in concentrations that are found in fetuses, mothers, and mother’s milk. 

  3. Although most of us ingest BPA daily, it is metabolized quickly. Recent studies have shown that BPA in canned soups and similar products causes a spike in serum BPA, followed by a rapid fall back to preingestion levels. Some critics conclude from this that BPA cannot be around long enough to cause harm.

The real situation, however, is more complicated. 

First, clearance may not be functionally permanent. Most clearance is by conjugation to glucuronate, a frequent mechanism to clear hormones, chemicals, and drugs from the blood. However, the enzyme glucuronidase can deconjugate BPA from glucuronate, and significant levels of glucuronidase are present in many tissues. In the case of the breast, biologically active glucuronidase is present in mother’s milk and, for example, contributes to neonatal jaundice by deconjugating the baby’s bilirubin in the gut. It is difficult to expect that the BPA known to be in human breast milk would not be activated the same way.

Second, it is argued that BPA rises and falls too quickly to cause harm, but this ignores what reproductive endocrinologists have known for years. Reproduction responds to spikes in hormone levels as much or more as to constantly elevated hormone levels. It may be that spikes, such as from a preadolescent eating BPA-rich food, would pose a greater risk.

These studies do not imply that BPA by itself causes breast cancer, but rather the estrogenic activity of BPA causes changes that promote breast cancer. The cancer-promoting properties of estrogens are the reason millions of women discontinued menopausal hormone replacement therapy after the Women’s Health Initiative showed that combination estrogen plus progestin therapy increased breast cancer. Unfortunately, women living in the United States cannot decide to discontinue their exposure to BPA. BPA is present in food packaging, house dust, cash register receipts, etc., such that 95 percent of Americans and 90 percent of Canadians test positive for BPA in their urine.

Thirty years ago, Lippman and Bolan recognized the importance of cell culture “ . . . in the analysis of estrogen action in nonmalignant tissue . . . ” In our work with nonmalignant cells, we have identified six different major cell features that are altered by BPA in ways that promote hallmark, cancer-like behavior in previously benign cells. The irony in this battle of spin is that if we had a drug that turned off cancer cells in culture as much as BPA turns them on, if we had data showing a clear mechanism of action like we have for BPA, and if we had as much supportive animal exposure data as already exists for BPA, the hypothetical drug would be expeditiously lined up for clinical trials.

It is time for responsible parents and grandparents to demand an end to the battle of spin. Calm minds must sort through the facts objectively and design and perform the studies needed to resolve pertinent questions.

William H. Goodson III, MD, is a breast cancer specialist, senior clinical research scientist at CPMC Research Institute, and former a SFMS president. Shanaz H. Dairkee, PhD, is senior scientist, CPMC Research Institute.


References

  1. Carwile JL, Ye X, Xiaoliu Z, Calafat AM, Michels KB. Canned soup consumption and urinary bisphenol A: A randomized crossover trial. JAMA. 2011; 306(20):2218-2220.
  2. Dairkee SH, Seok J, Champion S, Sayeed A, Mindrinos M, Xiao W, Davis RW, Goodson WH. Bisphenol A induces a profile of tumor aggressiveness in high-risk cells from breast cancer patients. Cancer Res. 2008; 68(7):2076-80.
  3. Goodson WH III, Luciani MG, Sayeed SA, Jaffee IM, Moore DH II, Dairkee SH. Activation of the mTOR pathway by low levels of xenoestrogens in breast epithelial cells from high-risk women. Carcinogenesis. 2011; 32(11):1724-33.
  4. Teeguarden JG, Calafat AM, Ye X, Doerge DR, Churchwell MI, Gunawan R, Graham MK. Twenty-four hour human urine and serum profiles of bisphenol a during high-dietary exposure. Toxicol Sci. 2011; 123(1):48-57.

SFMS Member Among SF Bay Area’s Most Influential Women in Business

Toni Brayer, MDToni Brayer, MD, member and past president of SFMS, has been named one of the “Most Influential Women in Bay Area Business” by the San Francisco Business Times. The honorable distinction is given to woman executives who are shaping Bay Area companies and communities.

Dr. Brayer has been a SFMS member since 1988. She is the vice president and chief medical officer for Sutter Health’s Bay Area Region and practices Internal Medicine at CPMC. She has written extensively about health care issues, public policy, and quality on her blog--EverythingHealth--and is a recognized physician leader.

Dr. Brayer will be honored at a gala dinner awards celebration on June 7 at the Hilton San Francisco.

Education: BS, Arizona State University; MD, University of Arizona

Community Involvement: Make-A-Wish Foundation board; Medical Insurance Exchange of California board; Women’s Initiative for Self Employment

Proudest professional accomplishment: Blazing the way for women in medical leadership as first (and only, still) woman chief of staff at California Pacific Medical Center, and the only woman chief medical officer at Sutter Health.

Best strategy for success in a tough economy: Be grateful for all you have and remember to help others who have it tougher. Think thrifty, not poor.

What makes you influential: I am very focused and can be counted on to deliver the goods. I put out good energy, am open and candid, and maintain broad relationships with all types of people.

Source: San Francisco Business Times, Special Supplement Issue, April 27-May 3, 2012. 


SFMS Members Honored for Volunteer Efforts

Three SFMS members were recently recognized by Operation Access for their dedication and volunteerism to provide essential surgical and specialty care to Bay Area’s underserved community. Please join SFMS in congratulating our selfless physicians for their contribution to improving access to health care. Michelle Li, MD is a general surgeon at California Pacific Medical Center (CPMC) who has been volunteering since 2006. She consistently sees one patient per month to provide donated surgeries such as hernia repair and cholecystectomy among an array of other procedures. Heidi Wittenberg, MD, also a CPMC physician, is the only urogynocologist in the Operation Access program. Since she started last year, Heidi has been consistently seeing patients and provides life-changing surgeries to women who had been suffering with these conditions for years. Elaine Yutan, MD is a general surgeon at Kaiser Permanente San Francisco who has been a volunteer with Operation Access for more than 10 years and continues to play a crucial role in every surgery session we organize at the hospital. In her time with the program, she had provided 86 services. Operation Access is a non-profit that mobilizes a network of medical volunteers, hospitals, and referring community clinics to provide low-income, uninsured people access to donated outpatient surgeries and specialty care that improve their health, ability to work and quality of life. Since 1993, the San Francisco-based organization has coordinated $50 million in charity care and arranged outpatient surgical care and specialty procedures for more than 6,000 patients in the Bay Area. For more information regarding Operation Access, please visit http://www.operationaccess.org/.

SFMS Career Fair a Success

The SFMS second annual Career Fair enjoyed a great turnout. On September 27, over seventy residents and fellows from local residency programs connected with recruiters from nineteen exhibiting organizations representing variety of practice types and settings based in San Francisco Bay Area. Many residents felt this was a wonderful opportunity to become acquainted with practice position opportunities and choices available in their specialty in San Francisco Bay Area, and highlight small clinics and groups that may have been overlooked by regional or national job search events. One event attendee commented, “Thank you for organizing an event that showcases the Bay Area’s local community clinics. This event is unlike any other because of the emphasis on San Francisco Bay Area job opportunities.” For those that missed the career fair, SFMS will be publishing a list of available positions and recruiter contact information in our November member-only eNewsletter. SFMS is already planning for next year’s event, tentatively scheduled for September 2012 at St. Mary’s Medical Center. SFMS would like to thank the California Pacific Medical Center for providing the venue for this event. We would also like to recognize our participating exhibitors and staff at the graduate medical departments of CPMC, UCSF, St. Mary’s, and Kaiser Permanente for their generosity and support.

EXHIBITORS

Asian Health Services
Brown & Toland
Cardiovascular Medical Group
Chinese Hospital
CHW Medical Foundation
CPMC/Sutter Health
Haight-Ashbury Free Clinics – Walden House
La Clinica de La Raza
Malin, Aubry, Gores, Wang, Haddad, and Sankaran
Marin Hospitalist Medical Group/Marin General Hospital
My Doctor Medical Group
Native American Health Center
NorthEast Medical Services (NEMS)
One Medical Group
The Permanente Medical Group/Kaiser Permanente
San Francisco Community Clinic Consortium
San Francisco Department of Public Health
Sonora Regional Medical Center

SFMS Past-President’s Environmental Health Research Featured as Chronicle Cover Story

William Goodson, MD, breast cancer specialist and a past-president of the SFMS, has been toiling on some innovative research for over a decade.  His publication of some results were featured in a cover story in the San Francisco Chronicle in September, with the title “Study: BPA, methylparaben block breast cancer drugs”. Goodson, senior clinical research scientist at California Pacific Medical Center Research Institute and lead author of the study published in the journal Carcinogenesis, noted that BPA and methylparaben not only mimic estrogen's ability to drive cancer, but appear to be even better than the natural hormone in bypassing the ability of drugs to treat it. [caption id="" align="alignright" width="333" caption="Photo: Lacy Atkins / The Chronicle"][/caption] Goodson attributes his interest in this field to meetings at the SFMS and editorials he wrote in San Francisco Medicine while serving as SFMS president in 1999.  He served as faculty at early meetings of the Collaborative on Health and the Environment, founded at the SFMS in 2002.  As for the chemical he studied for this paper, as he concluded in the Chronicle, "It's used so much. We kind of swim in it.” Goodson plans to continue with more research in this arena. The Carcinogenesis article: http://carcin.oxfordjournals.org/content/early/2011/09/01/carcin.bgr196.abstract?sid=ed031383-0b51-49c1-b768-02b7b5b80054 The Chronicle article: http://www.sfgate.com/cgi-bin/article.cgi?f=/c/a/2011/09/12/MN2U1L2ERJ.DTL#ixzz1Y44FJeEu The Collaborative on Health and the Environment: http://www.healthandenvironment.org

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