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Breast screening in women aged 40–49 years
Accepting survival statistics from the two published studies,2,3 both of which originated between 1978 and 1981, as an indicator of the appropriateness of a screening procedure at the present time may be inappropriate. Current and future treatments may improve the future statistics for long-term survival of patients currently detected by mammographic screening. The issue should not be the suggestion that any segment of the population be excluded, but rather a rational discussion of who should pay for screening under what circumstances. As noted by Gail and Rimer,4 any woman aged 40–49 years who shared the same risk for developing breast cancer as a woman aged 50 or greater would certainly qualify for screening. One would then have to quantify risk on an individual basis for those at increased risk. It would then have to be determined, should controversy continue, who should pay for mammography in women at low or no increased risk of breast cancer. We should not address all women in a particular decade of life with the implication that they share equal risk. *Murray H Seltzer, Janette H McDermott Department of Surgery, University of Medicine and Dentistry of New Jersey, New Jersey College of Medicine, Newark, NJ; Department of Surgery, St Barnabas Medical Center, Livingston, NJ; and *Practice Limited to Surgical Diseases of the Breast, PO Box 1845, Livingston, NJ 07039, USA 1
Dickersin K. Breast screening in women aged 40–49 years: what next? Lancet 1999; 353: 1896–97. 2 Alexander FE, Anderson TJ, Brown HK, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999; 353: 1903–08. 3 UK Trial of Early Detection of Breast Cancer group. 16-year mortality from breast cancer in the UK Trial of Early Detection of Breast Cancer. Lancet 1999; 353: 1909–14. 4 Gail M, Rimer B. Risk-based recommendations for mammographic screening for women in their forties. J Clin Oncol 1998; 16: 3105–14.
Author’s reply Sir—D W van Bekkum takes issue with the fact that I am from the USA and commented on UK studies. I fail to see the problem. If research evidence applied only to the country in which it was generated, patients and their doctors would have little to guide them in selecting the right care. Furthermore, I am not sure what is “widely” different between the USA and Europe. Irrespective of who pays for health care, women are afraid of breast cancer and currently depend on mammography as the only available means to detect it early.
THE LANCET • Vol 354 • September 11, 1999
I did not discuss the NCI recommendations or the results of the other randomised trials of mammography for women aged 40–49, mainly because that territory has been well covered in the literature. It is unlikely that either he or I or others who have been thinking about these issues for a long time would be swayed in our opinions by yet another critical review of the existing trials. My point was that the issue of screening women aged 40–49 is no longer just scientific, it is also political. Van Bekkum states that the best way to decrease the risks associated with a diagnosis of breast cancer is through early detection by mammography. One of the main difficulties with screening younger women is the low prevalence of breast cancer in this age group resulting in a rather large number of women who have false-positive results and must return for further testing, including biopsies. In addition, mammography frequently detects ductal carcinoma in situ (DCIS), a breast condition that progresses in some but not all women to invasive cancer. Because it is not possible to predict when DCIS will progress, women with DCIS are commonly treated as if they have invasive breast cancer, for example with mastectomy. Daniel Kopans is correct that discussion of the efficacy of mammographic screening seems to imply inappropriately a special significance to age 50. Age groups originally constructed for the purpose of statistical analysis have perhaps become firmly entrenched because age 50 is seen as a surrogate for menopause, when the risk of breast cancer and the sensitivity of mammography do in fact increase. What we all really want to know is: at what age should women begin mammographic screening? Unfortunately, no trial has addressed this question so far. And with the exception of the Canadian trial,1 none of the available data are from randomised trials specifically designed to address the efficacy of screening women in their forties. The Canadian trial showed no benefit to screening in this age group. The benefit shown by F Alexander and colleagues’ Edinburgh trial,2 was not apparent while the participating women were still in their forties, but only when they had reached their fifties. Kopans’ major criticism centres on combining results in a systematic review and meta-analysis, yet he has not specified how such an analysis might “skew” interpretation. Indeed, the objective of a systematic review is to apply scientific principles to reviewing
research. Thus, it is correct to take all available high-quality evidence into consideration when making a treatment decision or setting policy. Would Kopans prefer instead that a nonsystematic method of combining data or just selected individual studies be used to inform decision making? In describing the distribution of age at diagnosis of breast cancer, I did not intend to trivialise a breast cancer diagnosis at any age. I agree that the importance of DCIS to the issue of mammographic screening in women 40–49 is not trivial, but I known of no evidence that the mortality reduction that accrued more than 10 years after the start of the Edinburgh or Swedish trials is the result of an intervention in women with DCIS. Kay Dickersin Department of Community Health, School of Medicine, Brown University, Providence, RI 02912, USA (e-mail: [email protected]) 1
2
Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: In: Beast cancer detection and death rates among women aged 40 to 49 years. Can Med Assoc J 1992; 147: 1459–76. Alexander FE, Alderson TJ, Forrest APM, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999; 353: 1903–08.
Sir—In the summary of their report on the Edinburgh study of breast cancer screening, F E Alexander and colleagues (June 5, p 1903),1 conclude that “the results for younger women suggest benefit from introduction of screening before 50 years of age”. However, earlier in the summary they note that “no breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years”. Although screening was associated with a (non-significant) reduction in breast cancer mortality for women who entered the trial at ages 45–49, all the benefit these women experienced was derived from cancers detected by screening that occurred after they turned 50, which would seem to argue against screening before age 50. *Virginia L Ernster, Karla Kerlikowske Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA 94143, USA (e-mail: [email protected]) 1
Alexander FE, Anderson TJ, Brown HK, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999; 353: 1903–09.
Author’s reply Sir—Interpretation of the analysis that Virginia Ernster and Karla Kerlikowske cite has to be made very carefully, as we noted in our report, because the
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Dickersin K. Breast screening in women aged 40–49 years: what next? Lancet 1999; 353: 1896–97. 2 Alexander FE, Anderson TJ, Brown HK, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999; 353: 1903–08. 3 UK Trial of Early Detection of Breast Cancer group. 16-year mortality from breast cancer in the UK Trial of Early Detection of Breast Cancer. Lancet 1999; 353: 1909–14. 4 Gail M, Rimer B. Risk-based recommendations for mammographic screening for women in their forties. J Clin Oncol 1998; 16: 3105–14.
Author’s reply Sir—D W van Bekkum takes issue with the fact that I am from the USA and commented on UK studies. I fail to see the problem. If research evidence applied only to the country in which it was generated, patients and their doctors would have little to guide them in selecting the right care. Furthermore, I am not sure what is “widely” different between the USA and Europe. Irrespective of who pays for health care, women are afraid of breast cancer and currently depend on mammography as the only available means to detect it early.
THE LANCET • Vol 354 • September 11, 1999
I did not discuss the NCI recommendations or the results of the other randomised trials of mammography for women aged 40–49, mainly because that territory has been well covered in the literature. It is unlikely that either he or I or others who have been thinking about these issues for a long time would be swayed in our opinions by yet another critical review of the existing trials. My point was that the issue of screening women aged 40–49 is no longer just scientific, it is also political. Van Bekkum states that the best way to decrease the risks associated with a diagnosis of breast cancer is through early detection by mammography. One of the main difficulties with screening younger women is the low prevalence of breast cancer in this age group resulting in a rather large number of women who have false-positive results and must return for further testing, including biopsies. In addition, mammography frequently detects ductal carcinoma in situ (DCIS), a breast condition that progresses in some but not all women to invasive cancer. Because it is not possible to predict when DCIS will progress, women with DCIS are commonly treated as if they have invasive breast cancer, for example with mastectomy. Daniel Kopans is correct that discussion of the efficacy of mammographic screening seems to imply inappropriately a special significance to age 50. Age groups originally constructed for the purpose of statistical analysis have perhaps become firmly entrenched because age 50 is seen as a surrogate for menopause, when the risk of breast cancer and the sensitivity of mammography do in fact increase. What we all really want to know is: at what age should women begin mammographic screening? Unfortunately, no trial has addressed this question so far. And with the exception of the Canadian trial,1 none of the available data are from randomised trials specifically designed to address the efficacy of screening women in their forties. The Canadian trial showed no benefit to screening in this age group. The benefit shown by F Alexander and colleagues’ Edinburgh trial,2 was not apparent while the participating women were still in their forties, but only when they had reached their fifties. Kopans’ major criticism centres on combining results in a systematic review and meta-analysis, yet he has not specified how such an analysis might “skew” interpretation. Indeed, the objective of a systematic review is to apply scientific principles to reviewing
research. Thus, it is correct to take all available high-quality evidence into consideration when making a treatment decision or setting policy. Would Kopans prefer instead that a nonsystematic method of combining data or just selected individual studies be used to inform decision making? In describing the distribution of age at diagnosis of breast cancer, I did not intend to trivialise a breast cancer diagnosis at any age. I agree that the importance of DCIS to the issue of mammographic screening in women 40–49 is not trivial, but I known of no evidence that the mortality reduction that accrued more than 10 years after the start of the Edinburgh or Swedish trials is the result of an intervention in women with DCIS. Kay Dickersin Department of Community Health, School of Medicine, Brown University, Providence, RI 02912, USA (e-mail: [email protected]) 1
2
Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: In: Beast cancer detection and death rates among women aged 40 to 49 years. Can Med Assoc J 1992; 147: 1459–76. Alexander FE, Alderson TJ, Forrest APM, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999; 353: 1903–08.
Sir—In the summary of their report on the Edinburgh study of breast cancer screening, F E Alexander and colleagues (June 5, p 1903),1 conclude that “the results for younger women suggest benefit from introduction of screening before 50 years of age”. However, earlier in the summary they note that “no breast-cancer mortality benefit was observed for women whose breast cancers were diagnosed when they were younger than 50 years”. Although screening was associated with a (non-significant) reduction in breast cancer mortality for women who entered the trial at ages 45–49, all the benefit these women experienced was derived from cancers detected by screening that occurred after they turned 50, which would seem to argue against screening before age 50. *Virginia L Ernster, Karla Kerlikowske Department of Epidemiology and Biostatistics, School of Medicine, University of California San Francisco, San Francisco, CA 94143, USA (e-mail: [email protected]) 1
Alexander FE, Anderson TJ, Brown HK, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999; 353: 1903–09.
Author’s reply Sir—Interpretation of the analysis that Virginia Ernster and Karla Kerlikowske cite has to be made very carefully, as we noted in our report, because the
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