Opinion ID: 1381810
Heading Depth: 3
Heading Rank: 2

Heading: Wyeth's Reaction to Hormone Replacement Therapy Being Linked to Breast Cancer

Text: By 1976, the medical community began questioning whether there was a connection between estrogens and breast cancer. In an internal memo dated June 14, 1976, Wyeth doctors recognized that there is valid concern as to whether or not the use of exogenous estrogen leads to an increase in the incidence of breast cancer, but the memo ultimately concluded that [e]strogen use does not appear to bring about an increased risk of breast cancer. The following month, Dr. Robert Hoover of the National Cancer Institute at the NIH sent a manuscript of his forthcoming study on menopausal estrogens and breast cancer to Wyeth. [3] Dr. Hoover had concluded that estrogens may be a risk factor for breast cancer, and the study found a 2.0 relative risk [4] for women using estrogen for fifteen years or more. Dr. Hoover's letter stated that his study's findings were cause for grave concern and that more intensive study was necessary. Faced with the upcoming publication of Dr. Hoover's study in the New England Journal of Medicine, Wyeth prepared to defend Premarin. Internal correspondence stated that it was crucial to formulate a plan to mitigate the possible adverse effects of the study. The correspondence suggested prioritizing the refutation, or mitigation of the effects of Dr. Hoover's study, concluding that Wyeth could not afford to wait for the axe to start its descent before we give serious attention to how we might blunt its edge. Internal documents also showed a concern that the breast cancer risk was being overstated and that the study might affect Premarin's labeling requirements. A Wyeth-sponsored case-control study [5] on mammary cancer was considered, but never materialized. Prescriptions for estrogen in combination with progestin were on the rise, and as a Wyeth document stated, the number of published, well-designed studies [was] small or practically non existent. In the late 1980s and early 1990s, additional studies linked hormone replacement therapy to an increased risk of breast cancer. In 1989, Dr. Leif Bergkvist published the results of his long-term study of the risk of breast cancer following estrogen and estrogen-progestin replacement. Although the study had a small sample size, it nonetheless concluded that treatment with estrogens seems to be associated with a slightly increased risk of breast cancer, which is not prevented and may even be increased by the addition of progestins. This conclusion was contrary to the prevailing view that progestins might decrease the risk of breast cancer in much the same way that they decreased the risk of endometrial cancer. In 1990, Wyeth obtained information that Dr. Graham Colditz would present the results of a study showing that Premarin increased the risk of breast cancer by thirty percent in current users. The presentation was scheduled to take place at a meeting of the Society of Epidemiologic Research. Wyeth prepared talking points in advance of the meeting, planning to effectively position[] the risks vs. benefits so there is some counterbalance to potential negative news. Wyeth implemented a similar plan in response to the International Agency for Research on Cancer's (IARC) [6] announcement that it would evaluate the carcinogenic risks of estrogen replacement therapy. Justin Victoria, Wyeth's Associate Director of Regulatory Affairs, proposed the formation of a task force to ensure that IARC does not develop a position on a definitive relationship between breast cancer and estrogen replacement therapy as well as to ensure that conjugated estrogens are not singled out from other estrogen replacement therapies as any different in terms of carcinogenic risk. Throughout the 1990s, Wyeth remained vigilant in disassociating its product from cancer. In accordance with company policy, Wyeth denied the Eastern Cooperative Oncology Group's 1993 request for a supply of Premarin to conduct a study of hormone replacement therapy in women who have breast cancer. Presumably, the request was denied because estrogen is contraindicated for breast cancer, but a later memo referred to a custom at Wyeth of denying requests for Premarin for studies involving breast cancer. In 1994, a Wyeth executive responded to the suggestion that a respected oncologist chair an upcoming meeting of Wyeth consultants with [n]o way having an oncologist chair this. NO NO NO NO & NO. In 1995, a British scientist requested mammograms used in previous Wyeth studies for a study on breast density in estrogen and progestin users. Wyeth agreed on condition that there be no review of issues currently under discussion in literature elsewhere reviewing HRT and breast cancer and that the Premarin Study Review Committee has an absolute and final right to comment on the content, emphasis and conclusions of any publication(s) and if there are any significant differences of opinion raised the scientist will agree to accept the views of the Premarin Study Review Committee. In 1996, an NIH-sponsored study, authored by Dr. Steven Cummings, concluded that the risk of breast cancer associated with hormone replacement therapy may have been substantially underestimated. Wyeth received an advanced abstract of the study and established a breast cancer task force in response. Wyeth's response plan involved the following strategy: shift attention to other cancers; characterize the study as just one more paper; and highlight flaws in the study's methodology. The task force's stated goal for an upcoming meeting of the American Society of Clinical Oncology was to [o]vershadow [the] Cummings data by directing media attention elsewhere. Handwritten notes regarding the study state keep U.S. press busy and dismiss/distract. Wyeth also engaged in the lawful, though questionable, practice of commissioning ghost written articles. In 2000, Wyeth tapped Dr. John Eden to author Breast Cancer and Progestins, but the true author was a technical writing company, hired to produce the manuscript for Wyeth's approval and Dr. Eden's editing. Wyeth submitted a project assignment with references, a timetable, and topics to address, such as why progestins may not be responsible for the incidence of breast cancer in hormone replacement therapy (HRT) users. The finished product was published in the Journal of Obstetrics and Gynecology, apparently without the publication's knowledge of the article's origins and with no reference to Wyeth. Other authors then cited to the article, including Wyeth's own Dr. Ginger Constantine, facilitating its absorption into the collection of reliable medical data. [7]