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Breast cancer and hormone-replacement therapy in the Million Women Study
Maturitas 46 (2003) 91 /92 www.elsevier.com/locate/maturitas
Critical comment
Breast cancer and hormone-replacement therapy in the Million Women Study P.G. Crosignani * I Clinica Ostetrica e Ginecologica, Universita` di Milano, Via Commenda, 12, 20122 Milan, Italy
The Million Women Study [1] was set up to investigate in an unselected population the effect of specific types of the HRT on incident and fatal breast cancer. The study recruited 1 084 110 UK women aged 50 /64 years between 1996 and 2001. Half the women had used HRT. The main findings were as follows: (1) Current users of HRT were more likely than ever users to develop breast cancer and die from it. The risk disappears in the past users. Relative risk
Current HRT Past HRT
Incidence
Mortality
1.66 1.01
1.22 1.05
(2) The only factor that seemed to modify materially the relative risk estimates was bodymass index. (3) Among the various hormonal preparations breast cancer incidence was significantly increased for current users of oestrogen only (RR 1.30), oestrogen /progestagen (RR 2.00) and tibolone (RR 1.45). * Tel.: /39-02-5032-0256; fax: /39-02-5032-0255. E-mail address: [email protected] Crosignani).
(P.G.
(4) The increase of the relative risk in estrogen only users varied for oral, transdermal and implanted formulations (1.32, 1.24 and 1.65, respectively). (5) In current users of each type of HRT the risk of breast cancer increased with the duration of use. 10 years use of HRT is estimated to result in five additional breast cancers per 1000 users of oestrogen-only preparation and 19 additional cancers per 1000 users of oestrogen /progestagen combinations. (6) The increased risk of endometrial cancer associated with the use of oestrogen-only preparations is the main reason to prescribe combined HRT. Since incidence of breast cancer in this age group is higher than that of endometrial cancer, the excess incidences is due largely to endometrial cancer for oestrogen-only HRT, whereas for combined HRT the excess is exclusively made up of breast cancers. The following comments can be made: 1) The relative risk of breast cancer in the estrogen/progestagen users is the same found in the Women’s Health Initiative trial [2]. Taking in account the modest continuation rate of HRT users, the quick disappearance of the risk after drug withdrawal is quite reassuring. Nevertheless, since HRT is an important treatment, it has to be used only when clearly indicated and discontinued as soon as possible.
0378-5122/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2003.09.002
92
P.G. Crosignani / Maturitas 46 (2003) 91 /92
2) Considering its frequency, obesity ‘‘per se’’, probably remains the first modifiable risk factor for breast cancer [3]. 3) The increased risk associated with the use of tibolone is one of the original contributions of the ‘‘Million Women study’’. This preparation is often considered a sort of SERM without harmful effect for the breast and for the endometrium [4]. 4) Specific breast cancer risk data linked to the different forms of estrogen delivery is also an original finding and after this study it seems reasonable to consider that all estrogen preparations increase the risk. 5) ‘‘Qui vult vitare Scillam incidit in Cariddim’’. After WHI and the Million Women studies the number of ‘‘complimentary’’ hysterectomy will increase. HRT is a very effective drug and all drugs show unwanted side effects. Incidentally, it will be helpful to know the risk associated with the long-term use of commonly used medications in 500 000 citizens. The practical conclusions to be drawn are: . For women distressed by postmenopausal symptoms HRT still is the best effective cure.
The treatment can be discontinued after few months in the vast majority of users. . Weight loss must be seriously advised in all obese patients. . For prevention of bone loss or skin aging HRT can be discussed as part of an integrated preventive programme. Any preventive intervention in healthy woman must be virtually free from major risk.
References [1] Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet 2003;362:419 /27. [2] Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomised controlled trial. J Am Med Assoc 2002;288:321 /33. [3] Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity and mortality from cancer in a prospectively studied cohort of US adults. New Engl J Med 2003;348:1625 /8. [4] Moore RA. Livial: a review of clinical studies. Br J Obstet Gynaecol 1999;106(Suppl. 19):1 /21.
Critical comment
Breast cancer and hormone-replacement therapy in the Million Women Study P.G. Crosignani * I Clinica Ostetrica e Ginecologica, Universita` di Milano, Via Commenda, 12, 20122 Milan, Italy
The Million Women Study [1] was set up to investigate in an unselected population the effect of specific types of the HRT on incident and fatal breast cancer. The study recruited 1 084 110 UK women aged 50 /64 years between 1996 and 2001. Half the women had used HRT. The main findings were as follows: (1) Current users of HRT were more likely than ever users to develop breast cancer and die from it. The risk disappears in the past users. Relative risk
Current HRT Past HRT
Incidence
Mortality
1.66 1.01
1.22 1.05
(2) The only factor that seemed to modify materially the relative risk estimates was bodymass index. (3) Among the various hormonal preparations breast cancer incidence was significantly increased for current users of oestrogen only (RR 1.30), oestrogen /progestagen (RR 2.00) and tibolone (RR 1.45). * Tel.: /39-02-5032-0256; fax: /39-02-5032-0255. E-mail address: [email protected] Crosignani).
(P.G.
(4) The increase of the relative risk in estrogen only users varied for oral, transdermal and implanted formulations (1.32, 1.24 and 1.65, respectively). (5) In current users of each type of HRT the risk of breast cancer increased with the duration of use. 10 years use of HRT is estimated to result in five additional breast cancers per 1000 users of oestrogen-only preparation and 19 additional cancers per 1000 users of oestrogen /progestagen combinations. (6) The increased risk of endometrial cancer associated with the use of oestrogen-only preparations is the main reason to prescribe combined HRT. Since incidence of breast cancer in this age group is higher than that of endometrial cancer, the excess incidences is due largely to endometrial cancer for oestrogen-only HRT, whereas for combined HRT the excess is exclusively made up of breast cancers. The following comments can be made: 1) The relative risk of breast cancer in the estrogen/progestagen users is the same found in the Women’s Health Initiative trial [2]. Taking in account the modest continuation rate of HRT users, the quick disappearance of the risk after drug withdrawal is quite reassuring. Nevertheless, since HRT is an important treatment, it has to be used only when clearly indicated and discontinued as soon as possible.
0378-5122/03/$ - see front matter # 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2003.09.002
92
P.G. Crosignani / Maturitas 46 (2003) 91 /92
2) Considering its frequency, obesity ‘‘per se’’, probably remains the first modifiable risk factor for breast cancer [3]. 3) The increased risk associated with the use of tibolone is one of the original contributions of the ‘‘Million Women study’’. This preparation is often considered a sort of SERM without harmful effect for the breast and for the endometrium [4]. 4) Specific breast cancer risk data linked to the different forms of estrogen delivery is also an original finding and after this study it seems reasonable to consider that all estrogen preparations increase the risk. 5) ‘‘Qui vult vitare Scillam incidit in Cariddim’’. After WHI and the Million Women studies the number of ‘‘complimentary’’ hysterectomy will increase. HRT is a very effective drug and all drugs show unwanted side effects. Incidentally, it will be helpful to know the risk associated with the long-term use of commonly used medications in 500 000 citizens. The practical conclusions to be drawn are: . For women distressed by postmenopausal symptoms HRT still is the best effective cure.
The treatment can be discontinued after few months in the vast majority of users. . Weight loss must be seriously advised in all obese patients. . For prevention of bone loss or skin aging HRT can be discussed as part of an integrated preventive programme. Any preventive intervention in healthy woman must be virtually free from major risk.
References [1] Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet 2003;362:419 /27. [2] Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women’s health initiative randomised controlled trial. J Am Med Assoc 2002;288:321 /33. [3] Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity and mortality from cancer in a prospectively studied cohort of US adults. New Engl J Med 2003;348:1625 /8. [4] Moore RA. Livial: a review of clinical studies. Br J Obstet Gynaecol 1999;106(Suppl. 19):1 /21.