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Abortion and breast cancer: a hard decision made harder
Personal view
Abortion and breast cancer
Abortion and breast cancer: a hard decision made harder Tim Davidson
Over recent years, concerns have been raised about a possible causal relation between induced abortion and subsequent breast cancer. The abrupt hormonal changes associated with termination of pregnancy may induce changes in breast epithelial cells at a stage when they are not fully differentiated and therefore more vulnerable to later development of breast cancer. This review examines the published evidence supporting and refuting this hypothesis and concludes that there are, to date, insufficient data to justify warning women of future breast-cancer risk when counselling them about abortion.
Terminal duct lobular unit Terminal duct Extra- Intralobular lobular
Lobule: composed of a cluster of acini
Lancet Oncol 2001; 2: 756–58
The protective effect of both pregnancy and young age at first full pregnancy on the subsequent risk of breast cancer has been recognised for many decades. Nulliparity and late age at first birth increase the lifetime risk of breast cancer, although women who have a first child after the age of 35 appear to be at even higher risk than nulliparous women.1 Societal changes in planning and size of families since World War II have been implicated in a rising incidence of breast cancer in more developed countries. Brind and colleagues2 concluded that women who undergo induced abortion increase their risk of developing breast cancer in later life by a factor greater than the loss of protection that the pregnancy might otherwise have conferred. Not unexpectedly, given the emotive nature of the abortion debate and the entrenched views of many on both sides of the ‘pro-life’ versus ‘pro-choice’ debate, the controversy has become both topical and heated. The hypothesis linking abortion and breast cancer3,4 postulates that undifferentiated breast epithelial cells are stimulated by the high concentrations of oestradiol released into the circulation by the corpus luteum in early pregnancy. With a full-term pregnancy, these cells achieve full differentiation, whereas after an induced abortion the breast retains proliferated and supposedly vulnerable cells, which are more susceptible to carcinogens in later years (Figure 1). Because many spontaneous abortions are associated with low circulating maternal oestrogen concentrations, it is also suggested that the risk is lower after spontaneous abortion than after induced abortion. There is no histopathological or morphological verification of any such epithelial susceptibility and the hypothesis remains just that – a theory only.
Published studies The meta-analysis by Brind and colleagues2 reviewed 28 reported series of induced abortion, which included 756
Figure 1. Abortion and breast cancer hypothesis. During pregnancy, epithelial cells proliferate in the terminal duct lobular units. When pregnancy ends prematurely, the protective effect from complete differentiation is not achieved. Having undergone proliferation, the terminal duct lobular units are more susceptible to carcinogenesis.
specific data on induced abortion and breast-cancer incidence. Because some study data were presented in more than one report, the 28 reports were judged to constitute 23 independent studies. Reports pertaining only to spontaneous abortion or to abortion without specifying whether induced or spontaneous were excluded from the meta-analysis. The odds ratios for developing breast cancer were calculated from an average weighted according to the inverse of the variance. Combining the reviewed results, they found an overall odds ratio for breast cancer of 1.3 (95% CI 1.2–1.4) in patients with previous induced abortion. Brind and colleagues concluded that induced abortion should be regarded as an independent risk factor for breast cancer, irrespective of parity or timing of abortion relative to the first term pregnancy, although they conceded that the increase in risk was relatively low. This review stimulated considerable debate in medical journals,5-8 and Brind has publicised his findings widely at pro-life meetings. Critics of the paper have raised concerns about the effect of potential bias in reaching the conclusion that there is a significant causal association. A simple numerical TD is a Consultant Breast Surgeon and Honorary Senior Lecturer in Surgery in the University Department of Surgery, Royal Free Hospital, London, UK. Correspondence: Tim Davidson ChM MRCP FRCS, University Department of Surgery, Royal Free Hospital, Pond Street, London NW3 2QG, UK. Tel: +44 (0)20 7830 2794. Fax: +44 (0)20 7830 2194. THE LANCET Oncology Vol 2 December 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Personal view
Abortion and breast cancer
count of papers finding an association, versus those finding no significant link, is clearly subject to publication bias. Furthermore, in case-control studies, a persistent problem is the selection of an appropriate control group, and recall bias (or reporting bias, ie under-reporting of induced abortions by controls) is acknowledged as a further major difficulty,9 for which accurate correction is impossible. About 180 000 terminations are performed annually in England and Wales and about 12 000 in Scotland; the Royal College of Obstetricians and Gynaecologists10 has estimated that at least a third of British women will have had an abortion by the age of 45. In the light of these statistics, it is apparent that healthy control women have been more reluctant to report on a controversial, emotionally charged subject such as induced abortion, than have patients with breast cancer. Differential under-reporting may therefore be a cause of spurious associations in some case-control studies. In societies where termination of pregnancy remains illegal, verification of data is even more difficult. The validity of case-control studies in investigating the association between abortion and breast cancer has been questioned by other investigators.11-12 In their review, Michels and Willett13 addressed the apparent inconsistencies between studies and considered possible biases in data collection, presentation, and analysis that might create spurious associations. They concluded that the relation between induced or spontaneous abortion and breast cancer risk is likely to be small or non-existent (Table 1). The systematic review by Wingo and co-workers14 included case-control and cohort studies. The researchers reviewed 32 epidemiological studies that provided data on type of abortion, timing of abortion in relation to first fullterm pregnancy, and age at first abortion. While recognising inconsistencies across the studies, they concluded that there was no definite association between abortion and breast cancer, and that breast-cancer risk did not appear to be associated with an increasing number of spontaneous or induced abortions. The data suggested a slightly increased risk among nulliparous women, but definitive conclusions were not possible because of the small numbers of these in the study. The review by Wingo and co-workers14 has been included in the Cochrane Library’s Database of Reviews of Effectiveness and therefore meets the quality criteria required by the Cochrane Collaboration. Analysis of a Dutch population-based case-control study by Rookus and Van Leeuwen15 addressed the question of recall bias, and the effect of social bias with
Search strategy and selection criteria References for this review were identified by a search of MEDLINE for the years 1977 to 2001, using both the Medley and Ovid databases to include publications in all languages identified with the key words ‘abortion’ and ‘breast cancer’.
different outcomes in the predominantly Catholic southeast Netherlands, where the odds ratio exceeded that in the mainly Protestant western region. Case-control studies from Wisconsin,16 Boston,17 Italy,18 and Greece19 and Slovenia20 have shown either no significant risk after induced abortion, or a weak association, equivalent to the loss of the long-term protective effect of full-term pregnancy. A large Danish cohort study of 1.5 million women21 found that, on a population basis, induced abortion was not associated with an increased risk of breast cancer, with an odds ratio of 1.00 (95% CI 0.94–1.06). A recent case-control record linkage study from Oxford,22 which avoided the potential bias of case-control interview studies, found previous abortion to be slightly less common in women with breast cancer than in controls. An earlier Swedish cohort study23 followed up practically all Swedish women with a history of legal abortion in the first trimester before the age of 30 and found no overall increased risk of breast cancer (odds ratio 0.80; 95% CI 0.58–0.99), although this study has been criticised for its short follow-up period. A recent review of all the available published data by Bartholomew and Grimes24 again underlined the inconsistent results from case-control studies, whereas the large cohort studies, which are less susceptible to bias, showed either protection or no effect on breast-cancer risk from an induced abortion. Their conclusion supported a Class B recommendation (ie fair evidence) that induced abortion does not increase a woman’s risk of breast cancer later in life.
Conclusions How should the clinician proceed when dealing with a patient considering induced abortion? Primum non nocere, first do no harm, is a guiding tenet that must not be lost in the face of uncertain or confounding information. In the absence of robust evidence that an increased risk of breast cancer in later life is relevant to her deliberations, a woman deciding whether to opt for termination or to continue with an unwanted pregnancy has a hard enough task
Table 1. Literature reviews and meta-analyses Authors Michels and Willett 1996
Ref 13
Studies considered Case-control and cohort studies
Brind et al 1996
2
Wingo et al 1997
14
Case-control studies of induced abortion (spontaneous abortion excluded) Case-control and cohort studies
Bartholomew and Grimes 1998
24
Case-control and cohort studies
THE LANCET Oncology Vol 2 December 2001
Conclusions Data inadequate to infer a significant relation which is likely to be small or non-existent Abortion is a significant independent risk factor for breast cancer No increase with abortion except possible slight increase in nulliparous women No increase in breast cancer with spontaneous or induced abortion
757
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Personal view without being made to confront the breast-cancer issue. Until consistent and conclusive evidence of a causal link can be shown, her decision need not be made more difficult by having to entertain hypothetical future risks – a view endorsed by the Royal College of Obstetricians and Gynaecologists.25 Similarly, for the woman who develops breast cancer, the malignant disease that remains the largest killer of women in the UK between the ages of 30 and 50, there can be no possible advantage in stressing an unproven link with an abortion she underwent at an earlier stage in her life. To add a sense of guilt to the anxiety and despair that every woman faces at the time of breast-cancer diagnosis is nothing more than unnecessary cruelty. Abortion is a crisis in a woman’s life, inevitably a life or death decision for the foetus, and a potential source of psychological distress for the mother who makes the choice. For future epidemiological studies in breast cancer, more work is needed in specific areas where a stronger association might exist, such as in late second-trimester abortions,26 in very young patients,27 and in families with a genetic predisposition (eg carriers of BRCA 1 and BRCA 2 genes).28 From our current knowledge on abortion and breast cancer, the topic should be put to one side as far as the individual is concerned. Personal bias has no place here. References
1 McPherson K, Steele CM, Dixon JM. Breast cancer epidemiology, risk factors and genetics. In: Dixon JM (Ed). ABC of breast diseases. London: BMJ Publications, 2000: 624–28. 2 Brind J, Chinchilli VM, Severs WB, Summy-Long J. Induced abortion as an independent risk factor for breast cancer: a comprehensive review and meta-analysis. J Epidemiol Community Health 1996; 50: 481–96. 3 Russo J, Russo IH. Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumour incidence. Am J Pathol 1980; 100: 497–512. 4 Krieger N. Exposure, susceptibility, and breast cancer risk: a hypothesis regarding exogenous carcinogens, breast tissue development, and social gradients, including black/white differences, in breast cancer incidence. Br Cancer Res Treat 1989; 13: 205–32. 4 Melbye M, Wohlfahrt J, Olsen JH, et al. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 81–85. 5 Blettner M, Chang-Claude J, Scheuchenpflug T. Induced abortion as an independent risk factor for breast cancer. J Epidemiol Community Health 1997; 51: 465–67. 6 Canty L. Breast cancer risk: protective effect of an early first fullterm pregnancy versus increased risk of induced abortion. Oncol Nurs Forum 1997; 24: 1025–31. 7 Senghas RE, Dolan MF. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 1834; discussion 1835.
758
Abortion and breast cancer
8 Brind J, Chinchilli VM. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 1834; discussion 1835. 9 Tang MTC, Weiss NS, Daling JR et al. Case-control differences in the reliability of reporting a history of indiced abortion. Am J Epidemiol 2000; 151: 1139–43. 10 Abortion and breast cancer. Royal College of Obstetricians and Gynaecologists http://www.rcog.org.uk/press/press17.html, accessed October 2001. 11 Lindefors-Harris BM, Eklund G, Adami HO, Meirik O. Response bias in a case-control study: analysis utilizing comparative data concerning legal abortions from two independent Swedish studies. Am J Epidemiol 1991; 134: 1003–08. 12 Gammon MD, Bertin JE, Terry MB. Abortion and the risk of breast cancer. Is there a believable association? JAMA 1996; 275: 321–22. 13 Michels KB and Willett WC. Does induced or spontaneous abortion affect the risk of breast cancer? Epidemiology 1996; 7: 251–58. 14 Wingo PA, Newsome K, Marks JS. The risk of breast cancer following spontaneous or induced abortion. Cancer Causes Control. 1997; 8: 93–108. 15 Rookus MA, Van Leeuwen FE. Induced abortion and risk of breast cancer: reporting (recall) bias in a Dutch case-control study. J Natl Cancer Inst 1996; 88: 1759–84. 16 Newcomb PA, Storer BE, Longnecker MP, et al. Pregnancy termination in relation to risk of breast cancer. JAMA 1996; 275: 283–87. 17 Palmer JR, Rosenberg L, Rao RS, et al. Induced and spontaneous abortion in relation to risk of breast cancer. Cancer Causes Control 1997; 8: 841–49. 18 Tavani A, La Vecchia C, Franceschi S, et al. Abortion and breast cancer risk. Int J Cancer 1996; 65: 401–05. 19 Lipworth F, Katsouyanni K, Ekbom A, et al. Abortion and the risk of breast cancer: a case-control study in Greece. Int J Cancer 1995; 61: 181–84. 20 Robertson C, Van den Donk M, Primic-Zakelj M, et al. The association between induced and spontaneous abortion and risk of breast cancer in Slovenian women aged 25–54. The Breast 2001; 10: 291–98. 21 Melbye M, Wohlfahrt J, Olsen JH et al. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 81–85. 22 Goldacre MJ, Kurina LM, Seegroatt V et al. Abortion and breast cancer: a case-control record linkage study. J Epidemiol Community Health 2001; 55: 336–37. 23 Lindefors-Harris BM, Eklund G, Meirik O, et al. Risk of cancer of the breast after legal abortion during first trimester: a Swedish register study. BMJ 1989; 299: 1430–32. 24 Bartholomew LL, Grimes DA. The alleged association between induced abortion and risk of breast cancer: biology or bias? Obstet Gynecol Surg 1998; 53: 708–14. 25 The care of women requesting induced abortion. Royal College of Obstetricians and Gynaecologists. www.rcog.org.uk/guidelines/abortion/abortion-contents.html, acessed October 2001. 26 Melbye M, Wohlfahrt J, Olsen JH, et al. Induced abortion and risk of breast cancer [Danish]. Ugeskr Laeger 1998; 160: 5178–82. 27 Tavani A, Gallus S, La Vecchia C, et al. Risk factors for breast cancer in women under 40 years. Eur J Cancer 1999; 35: 1361–67. 28 Andrieu N, Duffy SW, Rohan TE, et al. Familial risk, abortion and their interactive effect on the risk of breast cancer: a combined analysis of six case-control studies. Br J Cancer 1995; 72: 1744–51.
THE LANCET Oncology Vol 2 December 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Abortion and breast cancer
Abortion and breast cancer: a hard decision made harder Tim Davidson
Over recent years, concerns have been raised about a possible causal relation between induced abortion and subsequent breast cancer. The abrupt hormonal changes associated with termination of pregnancy may induce changes in breast epithelial cells at a stage when they are not fully differentiated and therefore more vulnerable to later development of breast cancer. This review examines the published evidence supporting and refuting this hypothesis and concludes that there are, to date, insufficient data to justify warning women of future breast-cancer risk when counselling them about abortion.
Terminal duct lobular unit Terminal duct Extra- Intralobular lobular
Lobule: composed of a cluster of acini
Lancet Oncol 2001; 2: 756–58
The protective effect of both pregnancy and young age at first full pregnancy on the subsequent risk of breast cancer has been recognised for many decades. Nulliparity and late age at first birth increase the lifetime risk of breast cancer, although women who have a first child after the age of 35 appear to be at even higher risk than nulliparous women.1 Societal changes in planning and size of families since World War II have been implicated in a rising incidence of breast cancer in more developed countries. Brind and colleagues2 concluded that women who undergo induced abortion increase their risk of developing breast cancer in later life by a factor greater than the loss of protection that the pregnancy might otherwise have conferred. Not unexpectedly, given the emotive nature of the abortion debate and the entrenched views of many on both sides of the ‘pro-life’ versus ‘pro-choice’ debate, the controversy has become both topical and heated. The hypothesis linking abortion and breast cancer3,4 postulates that undifferentiated breast epithelial cells are stimulated by the high concentrations of oestradiol released into the circulation by the corpus luteum in early pregnancy. With a full-term pregnancy, these cells achieve full differentiation, whereas after an induced abortion the breast retains proliferated and supposedly vulnerable cells, which are more susceptible to carcinogens in later years (Figure 1). Because many spontaneous abortions are associated with low circulating maternal oestrogen concentrations, it is also suggested that the risk is lower after spontaneous abortion than after induced abortion. There is no histopathological or morphological verification of any such epithelial susceptibility and the hypothesis remains just that – a theory only.
Published studies The meta-analysis by Brind and colleagues2 reviewed 28 reported series of induced abortion, which included 756
Figure 1. Abortion and breast cancer hypothesis. During pregnancy, epithelial cells proliferate in the terminal duct lobular units. When pregnancy ends prematurely, the protective effect from complete differentiation is not achieved. Having undergone proliferation, the terminal duct lobular units are more susceptible to carcinogenesis.
specific data on induced abortion and breast-cancer incidence. Because some study data were presented in more than one report, the 28 reports were judged to constitute 23 independent studies. Reports pertaining only to spontaneous abortion or to abortion without specifying whether induced or spontaneous were excluded from the meta-analysis. The odds ratios for developing breast cancer were calculated from an average weighted according to the inverse of the variance. Combining the reviewed results, they found an overall odds ratio for breast cancer of 1.3 (95% CI 1.2–1.4) in patients with previous induced abortion. Brind and colleagues concluded that induced abortion should be regarded as an independent risk factor for breast cancer, irrespective of parity or timing of abortion relative to the first term pregnancy, although they conceded that the increase in risk was relatively low. This review stimulated considerable debate in medical journals,5-8 and Brind has publicised his findings widely at pro-life meetings. Critics of the paper have raised concerns about the effect of potential bias in reaching the conclusion that there is a significant causal association. A simple numerical TD is a Consultant Breast Surgeon and Honorary Senior Lecturer in Surgery in the University Department of Surgery, Royal Free Hospital, London, UK. Correspondence: Tim Davidson ChM MRCP FRCS, University Department of Surgery, Royal Free Hospital, Pond Street, London NW3 2QG, UK. Tel: +44 (0)20 7830 2794. Fax: +44 (0)20 7830 2194. THE LANCET Oncology Vol 2 December 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Personal view
Abortion and breast cancer
count of papers finding an association, versus those finding no significant link, is clearly subject to publication bias. Furthermore, in case-control studies, a persistent problem is the selection of an appropriate control group, and recall bias (or reporting bias, ie under-reporting of induced abortions by controls) is acknowledged as a further major difficulty,9 for which accurate correction is impossible. About 180 000 terminations are performed annually in England and Wales and about 12 000 in Scotland; the Royal College of Obstetricians and Gynaecologists10 has estimated that at least a third of British women will have had an abortion by the age of 45. In the light of these statistics, it is apparent that healthy control women have been more reluctant to report on a controversial, emotionally charged subject such as induced abortion, than have patients with breast cancer. Differential under-reporting may therefore be a cause of spurious associations in some case-control studies. In societies where termination of pregnancy remains illegal, verification of data is even more difficult. The validity of case-control studies in investigating the association between abortion and breast cancer has been questioned by other investigators.11-12 In their review, Michels and Willett13 addressed the apparent inconsistencies between studies and considered possible biases in data collection, presentation, and analysis that might create spurious associations. They concluded that the relation between induced or spontaneous abortion and breast cancer risk is likely to be small or non-existent (Table 1). The systematic review by Wingo and co-workers14 included case-control and cohort studies. The researchers reviewed 32 epidemiological studies that provided data on type of abortion, timing of abortion in relation to first fullterm pregnancy, and age at first abortion. While recognising inconsistencies across the studies, they concluded that there was no definite association between abortion and breast cancer, and that breast-cancer risk did not appear to be associated with an increasing number of spontaneous or induced abortions. The data suggested a slightly increased risk among nulliparous women, but definitive conclusions were not possible because of the small numbers of these in the study. The review by Wingo and co-workers14 has been included in the Cochrane Library’s Database of Reviews of Effectiveness and therefore meets the quality criteria required by the Cochrane Collaboration. Analysis of a Dutch population-based case-control study by Rookus and Van Leeuwen15 addressed the question of recall bias, and the effect of social bias with
Search strategy and selection criteria References for this review were identified by a search of MEDLINE for the years 1977 to 2001, using both the Medley and Ovid databases to include publications in all languages identified with the key words ‘abortion’ and ‘breast cancer’.
different outcomes in the predominantly Catholic southeast Netherlands, where the odds ratio exceeded that in the mainly Protestant western region. Case-control studies from Wisconsin,16 Boston,17 Italy,18 and Greece19 and Slovenia20 have shown either no significant risk after induced abortion, or a weak association, equivalent to the loss of the long-term protective effect of full-term pregnancy. A large Danish cohort study of 1.5 million women21 found that, on a population basis, induced abortion was not associated with an increased risk of breast cancer, with an odds ratio of 1.00 (95% CI 0.94–1.06). A recent case-control record linkage study from Oxford,22 which avoided the potential bias of case-control interview studies, found previous abortion to be slightly less common in women with breast cancer than in controls. An earlier Swedish cohort study23 followed up practically all Swedish women with a history of legal abortion in the first trimester before the age of 30 and found no overall increased risk of breast cancer (odds ratio 0.80; 95% CI 0.58–0.99), although this study has been criticised for its short follow-up period. A recent review of all the available published data by Bartholomew and Grimes24 again underlined the inconsistent results from case-control studies, whereas the large cohort studies, which are less susceptible to bias, showed either protection or no effect on breast-cancer risk from an induced abortion. Their conclusion supported a Class B recommendation (ie fair evidence) that induced abortion does not increase a woman’s risk of breast cancer later in life.
Conclusions How should the clinician proceed when dealing with a patient considering induced abortion? Primum non nocere, first do no harm, is a guiding tenet that must not be lost in the face of uncertain or confounding information. In the absence of robust evidence that an increased risk of breast cancer in later life is relevant to her deliberations, a woman deciding whether to opt for termination or to continue with an unwanted pregnancy has a hard enough task
Table 1. Literature reviews and meta-analyses Authors Michels and Willett 1996
Ref 13
Studies considered Case-control and cohort studies
Brind et al 1996
2
Wingo et al 1997
14
Case-control studies of induced abortion (spontaneous abortion excluded) Case-control and cohort studies
Bartholomew and Grimes 1998
24
Case-control and cohort studies
THE LANCET Oncology Vol 2 December 2001
Conclusions Data inadequate to infer a significant relation which is likely to be small or non-existent Abortion is a significant independent risk factor for breast cancer No increase with abortion except possible slight increase in nulliparous women No increase in breast cancer with spontaneous or induced abortion
757
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Personal view without being made to confront the breast-cancer issue. Until consistent and conclusive evidence of a causal link can be shown, her decision need not be made more difficult by having to entertain hypothetical future risks – a view endorsed by the Royal College of Obstetricians and Gynaecologists.25 Similarly, for the woman who develops breast cancer, the malignant disease that remains the largest killer of women in the UK between the ages of 30 and 50, there can be no possible advantage in stressing an unproven link with an abortion she underwent at an earlier stage in her life. To add a sense of guilt to the anxiety and despair that every woman faces at the time of breast-cancer diagnosis is nothing more than unnecessary cruelty. Abortion is a crisis in a woman’s life, inevitably a life or death decision for the foetus, and a potential source of psychological distress for the mother who makes the choice. For future epidemiological studies in breast cancer, more work is needed in specific areas where a stronger association might exist, such as in late second-trimester abortions,26 in very young patients,27 and in families with a genetic predisposition (eg carriers of BRCA 1 and BRCA 2 genes).28 From our current knowledge on abortion and breast cancer, the topic should be put to one side as far as the individual is concerned. Personal bias has no place here. References
1 McPherson K, Steele CM, Dixon JM. Breast cancer epidemiology, risk factors and genetics. In: Dixon JM (Ed). ABC of breast diseases. London: BMJ Publications, 2000: 624–28. 2 Brind J, Chinchilli VM, Severs WB, Summy-Long J. Induced abortion as an independent risk factor for breast cancer: a comprehensive review and meta-analysis. J Epidemiol Community Health 1996; 50: 481–96. 3 Russo J, Russo IH. Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumour incidence. Am J Pathol 1980; 100: 497–512. 4 Krieger N. Exposure, susceptibility, and breast cancer risk: a hypothesis regarding exogenous carcinogens, breast tissue development, and social gradients, including black/white differences, in breast cancer incidence. Br Cancer Res Treat 1989; 13: 205–32. 4 Melbye M, Wohlfahrt J, Olsen JH, et al. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 81–85. 5 Blettner M, Chang-Claude J, Scheuchenpflug T. Induced abortion as an independent risk factor for breast cancer. J Epidemiol Community Health 1997; 51: 465–67. 6 Canty L. Breast cancer risk: protective effect of an early first fullterm pregnancy versus increased risk of induced abortion. Oncol Nurs Forum 1997; 24: 1025–31. 7 Senghas RE, Dolan MF. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 1834; discussion 1835.
758
Abortion and breast cancer
8 Brind J, Chinchilli VM. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 1834; discussion 1835. 9 Tang MTC, Weiss NS, Daling JR et al. Case-control differences in the reliability of reporting a history of indiced abortion. Am J Epidemiol 2000; 151: 1139–43. 10 Abortion and breast cancer. Royal College of Obstetricians and Gynaecologists http://www.rcog.org.uk/press/press17.html, accessed October 2001. 11 Lindefors-Harris BM, Eklund G, Adami HO, Meirik O. Response bias in a case-control study: analysis utilizing comparative data concerning legal abortions from two independent Swedish studies. Am J Epidemiol 1991; 134: 1003–08. 12 Gammon MD, Bertin JE, Terry MB. Abortion and the risk of breast cancer. Is there a believable association? JAMA 1996; 275: 321–22. 13 Michels KB and Willett WC. Does induced or spontaneous abortion affect the risk of breast cancer? Epidemiology 1996; 7: 251–58. 14 Wingo PA, Newsome K, Marks JS. The risk of breast cancer following spontaneous or induced abortion. Cancer Causes Control. 1997; 8: 93–108. 15 Rookus MA, Van Leeuwen FE. Induced abortion and risk of breast cancer: reporting (recall) bias in a Dutch case-control study. J Natl Cancer Inst 1996; 88: 1759–84. 16 Newcomb PA, Storer BE, Longnecker MP, et al. Pregnancy termination in relation to risk of breast cancer. JAMA 1996; 275: 283–87. 17 Palmer JR, Rosenberg L, Rao RS, et al. Induced and spontaneous abortion in relation to risk of breast cancer. Cancer Causes Control 1997; 8: 841–49. 18 Tavani A, La Vecchia C, Franceschi S, et al. Abortion and breast cancer risk. Int J Cancer 1996; 65: 401–05. 19 Lipworth F, Katsouyanni K, Ekbom A, et al. Abortion and the risk of breast cancer: a case-control study in Greece. Int J Cancer 1995; 61: 181–84. 20 Robertson C, Van den Donk M, Primic-Zakelj M, et al. The association between induced and spontaneous abortion and risk of breast cancer in Slovenian women aged 25–54. The Breast 2001; 10: 291–98. 21 Melbye M, Wohlfahrt J, Olsen JH et al. Induced abortion and the risk of breast cancer. N Engl J Med 1997; 336: 81–85. 22 Goldacre MJ, Kurina LM, Seegroatt V et al. Abortion and breast cancer: a case-control record linkage study. J Epidemiol Community Health 2001; 55: 336–37. 23 Lindefors-Harris BM, Eklund G, Meirik O, et al. Risk of cancer of the breast after legal abortion during first trimester: a Swedish register study. BMJ 1989; 299: 1430–32. 24 Bartholomew LL, Grimes DA. The alleged association between induced abortion and risk of breast cancer: biology or bias? Obstet Gynecol Surg 1998; 53: 708–14. 25 The care of women requesting induced abortion. Royal College of Obstetricians and Gynaecologists. www.rcog.org.uk/guidelines/abortion/abortion-contents.html, acessed October 2001. 26 Melbye M, Wohlfahrt J, Olsen JH, et al. Induced abortion and risk of breast cancer [Danish]. Ugeskr Laeger 1998; 160: 5178–82. 27 Tavani A, Gallus S, La Vecchia C, et al. Risk factors for breast cancer in women under 40 years. Eur J Cancer 1999; 35: 1361–67. 28 Andrieu N, Duffy SW, Rohan TE, et al. Familial risk, abortion and their interactive effect on the risk of breast cancer: a combined analysis of six case-control studies. Br J Cancer 1995; 72: 1744–51.
THE LANCET Oncology Vol 2 December 2001
For personal use. Only reproduce with permission from The Lancet Publishing Group.