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Oral oestrogen–progestagen contraceptives, menopausal treatment, and cancer
Reflection and Reaction
Oral oestrogen–progestagen contraceptives, menopausal treatment, and cancer
Lancet Oncol 2005; 6: 552–53
736
In August, 2005, The Lancet Oncology published a Policy Watch article1 that summarised evidence for the carcinogenicity of combined oestrogen–progestagen contraceptives and combined hormone-replacement therapy, established at a meeting of the Monograph Working Group in June, 2005, held by the International Agency for Research on Cancer (IARC). I was a participant of the Working Group. The Working Group concluded that there is sufficient evidence in human beings to classify combined oestrogen–progestagen contraceptives as carcinogenic to the breast and cervix (group 1), and to classify combined hormone-replacement therapy as carcinogenic to the breast (group 1). However, the Policy Watch article1 did not mention that I disagreed with those conclusions, and I wish to record this opinion. To give the reasons for my disagreement before the assessment has been published in full would be premature. However, to consider additional facts about the remit given by IARC to the Working Group is also necessary: these facts bear directly on the a priori scientific validity of the IARC Monograph presently in press.2 The terms of reference for the Working Group were restricted to combined oestrogen–progestagen products; the epidemiological evidence for single-ingredient products containing only an oestrogen or progestagen was not judged. I pointed out in the meeting that nearly all chemicals present in combination products are also present in single-ingredient products. Hence, assessment of combination products, while not addressing how the epidemiological evidence for single-ingredient products might affect that assessment, would inevitably be incomplete. These facts were not challenged, but it was argued that an assessment of single-ingredient products would not change the main conclusions for combination products. No evidence was presented to support that argument. It was also argued that to change the terms of reference would be too complicated and impractical at that late stage. The overall effect was that, by design, the resulting IARC Monograph is based on an incomplete assessment of the relevant evidence. Failure to take into account epidemiological evidence for single-ingredient products
was clearly an error, and one that could only have been corrected by the amendment of the terms of reference and by the adjournment of the proceedings to a later date. Samuel Shapiro Department of Public Health, University of Cape Town Medical School, Cape Town, South Africa [email protected] I have been sponsored by various pharmaceutical companies that manufacture oral contraceptives and supplemental female hormones to attend or lecture at conferences, to give expert testimonies, and to act as a consultant. 1
2
Cogliano V, Grosse Y, Baan R, et al. Carcinogenicity of combined oestrogen–progestagen contraceptives and menopausal treatment. Lancet Oncol 2005; 6: 552–53. IARC Monographs on the evaluation of carcinogenic risks to humans, volume 91, combined oestrogen-progestogen contraceptives and combined oestrogen-progestogen menopausal therapy. Lyon: International Agency for Research on Cancer (in press).
In the August issue of The Lancet Oncology, a Policy Watch article1 summarised an IARC Monograph, which is not due for publication for several months. The article suggested that the combined oral contraceptive pill was now regarded as a cause of both breast cancer and cervical cancer. I am not aware that causality has been proven in either cancer, although there is an association2,4,5 (an observed association does not necessarily imply a causal relation).6 Intrigued by this article, I would have liked to have checked which studies had been cited by the Monograph Working Group to support their statement, but the only reference provided in the Policy Watch article1 was the unpublished IARC Monograph. How are scientists, clinicians, and other interested parties supposed to assess the evidence? How do we know that the summary is an accurate representation of the full document? This situation makes it very difficult for those who interact with patients, who are understandably worried by the resultant reports in the media, to know what advice they should be giving. Although I fully understand that a journal that publishes breaking news stories might wish to report on the activities of the Monograph Working Group as early as possible, I question such a policy when the full Monograph will not be available for months, rather than days, afterwards. http://oncology.thelancet.com Vol 6 October 2005
Oral oestrogen–progestagen contraceptives, menopausal treatment, and cancer
Lancet Oncol 2005; 6: 552–53
736
In August, 2005, The Lancet Oncology published a Policy Watch article1 that summarised evidence for the carcinogenicity of combined oestrogen–progestagen contraceptives and combined hormone-replacement therapy, established at a meeting of the Monograph Working Group in June, 2005, held by the International Agency for Research on Cancer (IARC). I was a participant of the Working Group. The Working Group concluded that there is sufficient evidence in human beings to classify combined oestrogen–progestagen contraceptives as carcinogenic to the breast and cervix (group 1), and to classify combined hormone-replacement therapy as carcinogenic to the breast (group 1). However, the Policy Watch article1 did not mention that I disagreed with those conclusions, and I wish to record this opinion. To give the reasons for my disagreement before the assessment has been published in full would be premature. However, to consider additional facts about the remit given by IARC to the Working Group is also necessary: these facts bear directly on the a priori scientific validity of the IARC Monograph presently in press.2 The terms of reference for the Working Group were restricted to combined oestrogen–progestagen products; the epidemiological evidence for single-ingredient products containing only an oestrogen or progestagen was not judged. I pointed out in the meeting that nearly all chemicals present in combination products are also present in single-ingredient products. Hence, assessment of combination products, while not addressing how the epidemiological evidence for single-ingredient products might affect that assessment, would inevitably be incomplete. These facts were not challenged, but it was argued that an assessment of single-ingredient products would not change the main conclusions for combination products. No evidence was presented to support that argument. It was also argued that to change the terms of reference would be too complicated and impractical at that late stage. The overall effect was that, by design, the resulting IARC Monograph is based on an incomplete assessment of the relevant evidence. Failure to take into account epidemiological evidence for single-ingredient products
was clearly an error, and one that could only have been corrected by the amendment of the terms of reference and by the adjournment of the proceedings to a later date. Samuel Shapiro Department of Public Health, University of Cape Town Medical School, Cape Town, South Africa [email protected] I have been sponsored by various pharmaceutical companies that manufacture oral contraceptives and supplemental female hormones to attend or lecture at conferences, to give expert testimonies, and to act as a consultant. 1
2
Cogliano V, Grosse Y, Baan R, et al. Carcinogenicity of combined oestrogen–progestagen contraceptives and menopausal treatment. Lancet Oncol 2005; 6: 552–53. IARC Monographs on the evaluation of carcinogenic risks to humans, volume 91, combined oestrogen-progestogen contraceptives and combined oestrogen-progestogen menopausal therapy. Lyon: International Agency for Research on Cancer (in press).
In the August issue of The Lancet Oncology, a Policy Watch article1 summarised an IARC Monograph, which is not due for publication for several months. The article suggested that the combined oral contraceptive pill was now regarded as a cause of both breast cancer and cervical cancer. I am not aware that causality has been proven in either cancer, although there is an association2,4,5 (an observed association does not necessarily imply a causal relation).6 Intrigued by this article, I would have liked to have checked which studies had been cited by the Monograph Working Group to support their statement, but the only reference provided in the Policy Watch article1 was the unpublished IARC Monograph. How are scientists, clinicians, and other interested parties supposed to assess the evidence? How do we know that the summary is an accurate representation of the full document? This situation makes it very difficult for those who interact with patients, who are understandably worried by the resultant reports in the media, to know what advice they should be giving. Although I fully understand that a journal that publishes breaking news stories might wish to report on the activities of the Monograph Working Group as early as possible, I question such a policy when the full Monograph will not be available for months, rather than days, afterwards. http://oncology.thelancet.com Vol 6 October 2005