Therapeutics
Annual mammography screening did not reduce long-term breast cancer mortality in women 40 to 59 years of age
Miller AB, Wall C, Baines CJ, et al. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366.
Clinical impact rating: F ★★★★★★✩ Question In women 40 to 59 years of age, does annual screening with mammography for 5 years reduce long-term risk for breast cancer mortality more than usual care or annual screening without mammography?
Methods Design: Long-term follow-up of a randomized controlled trial (RCT) (Canadian National Breast Screening Study). Allocation: Concealed.* Blinding: Blinded* (cause of death adjudicators for deaths reported through treating surgeons in women with breast cancer). Follow-up period: ≤ 25 years (mean 22 y). Setting: 15 screening centers in Canada. Patients: 89 835 women who were 40 to 59 years of age, had no history of breast cancer, had not had a mammogram in the past 12 months, and were not pregnant. Intervention: 4 to 5 annual mammograms plus breast examinations (n = 44 925) or control (n = 44 910). In women 40 to 49 years of age (n = 50 430), the control group (n = 25 216) received usual care from their family doctors. In women 50 to 59 years of age (n = 39 405), the control group (n = 19 694) received 4 to 5 annual breast examinations. Outcomes: Breast cancer mortality. Secondary outcomes included breast cancer occurrence and overdiagnosis. Patient follow-up: 100% {intention-to-treat analysis}†.
Main results During the screening period and the total 25-year follow-up, breast cancer was detected in 1.5% and 7.2% of the mammography group and 1.2% and 7.0% of the control group. Groups did not differ for breast cancer mortality at a mean 22 years (Table). 22% of screen-detected invasive cases of breast cancer were overdiagnosed.
Conclusion In women 40 to 59 years of age, annual screening with mammography for 5 years does not reduce long-term risk for breast cancer mortality more than usual care or annual screening without mammography. *See Glossary. †Information provided by author.
Sources of funding: Canadian Breast Cancer Research Alliance; Canadian Breast Cancer Research Initiative; Canadian Cancer Annual mammography vs usual care or physical breast examination only for breast cancer mortality‡ Rate per 10 000 women Mammography Usual care
At a mean 22 y RRR (95% CI) NNT (CI)
108
1% (−12 to 12)
110
Not significant
‡Abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rate and hazard ratio in article.
20 May 2014 | ACP Journal Club | Volume 160 • Number 10 Downloaded From: http://annals.org/ by a McGill University User on 11/21/2014
Society; Health and Welfare Canada; National Cancer Institute of Canada; Alberta Heritage Fund for Cancer Research; Manitoba Health Services Commission; Medical Research Council of Canada; le Ministère de la Santé et des Services Soçiaux du Québec; Nova Scotia Department of Health; Ontario Ministry of Health. For correspondence: Dr. A.B. Miller, University of Toronto, Toronto, ON, Canada. E-mail [email protected]. ■
Commentary No breast cancer screening trial has endured more angry criticism than the Canadian National Breast Screening Study (NBSS). Even for women 50 to 59 years of age, other trials found decreased breast cancer mortality with mammography screening (1). Could NBSS be wrong, or at least a statistical outlier, despite its meticulous methods? Meta-analyses have not dealt with changing breast cancer treatments. The first RCT began 51 years ago; the NBSS started in the 1980s when it became evident that adjuvant therapies (used for NBSS patients) substantially reduced mortality rates, thus potentially affecting the benefit of screening. NBSS results strengthen evidence that mammography screening leads to overdiagnosis (screen-detected cancers that would not become clinically apparent during life). After 22 years, excess numbers of invasive cancer in the mammography group represented 22% of all screen-detected cancer and 50% of nonpalpable cancer. Including ductal carcinoma in situ would raise the percentage further. No RCT has evaluated effects of new screening technologies on breast cancer mortality; ironically, these may increase overdiagnosis by finding smaller tumors. The NBSS also raises the intriguing possibility that annual standardized clinical breast examinations lasting 5 to 10 minutes— which all women age 50 to 59 years received—may be as effective as mammography for decreasing breast cancer mortality. Women and clinicians need information, even if not exact, to make informed decisions about mammography screening (2, 3). Including old RCTs, if one thousand 50-year old women have annual mammograms for the next 10 years, about 600 will have ≥ 1 false-positive mammogram, 25 will be diagnosed with invasive breast cancer (of whom 5 to 6 will be overdiagnosed and treated unnecessarily), and 3 will be “cured” (alive because of mammography). If the NBSS results are correct, the number of “cured” drops to 0. Even if the small numbers are incorrect by 100%, they can help women better understand the benefits and harms of breast cancer screening. Suzanne W. Fletcher, MD Harvard Medical School Boston, Massachusetts, USA References 1. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012; 380:1778-86. 2. Fletcher RH, Fletcher SW, Fletcher GS. Clinical Epidemiology: The Essentials, 5th edition. Philadelphia: Lippincott Williams & Wilkins. 2014 3. Welch HG, Passow HJ. Quantifying the benefits and harms of screening mammography. JAMA Intern Med. 2014;174:448-54. © 2014 American College of Physicians
JC7
Annual mammography screening did not reduce long-term breast cancer mortality in women 40 to 59 years of age
Miller AB, Wall C, Baines CJ, et al. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366.
Clinical impact rating: F ★★★★★★✩ Question In women 40 to 59 years of age, does annual screening with mammography for 5 years reduce long-term risk for breast cancer mortality more than usual care or annual screening without mammography?
Methods Design: Long-term follow-up of a randomized controlled trial (RCT) (Canadian National Breast Screening Study). Allocation: Concealed.* Blinding: Blinded* (cause of death adjudicators for deaths reported through treating surgeons in women with breast cancer). Follow-up period: ≤ 25 years (mean 22 y). Setting: 15 screening centers in Canada. Patients: 89 835 women who were 40 to 59 years of age, had no history of breast cancer, had not had a mammogram in the past 12 months, and were not pregnant. Intervention: 4 to 5 annual mammograms plus breast examinations (n = 44 925) or control (n = 44 910). In women 40 to 49 years of age (n = 50 430), the control group (n = 25 216) received usual care from their family doctors. In women 50 to 59 years of age (n = 39 405), the control group (n = 19 694) received 4 to 5 annual breast examinations. Outcomes: Breast cancer mortality. Secondary outcomes included breast cancer occurrence and overdiagnosis. Patient follow-up: 100% {intention-to-treat analysis}†.
Main results During the screening period and the total 25-year follow-up, breast cancer was detected in 1.5% and 7.2% of the mammography group and 1.2% and 7.0% of the control group. Groups did not differ for breast cancer mortality at a mean 22 years (Table). 22% of screen-detected invasive cases of breast cancer were overdiagnosed.
Conclusion In women 40 to 59 years of age, annual screening with mammography for 5 years does not reduce long-term risk for breast cancer mortality more than usual care or annual screening without mammography. *See Glossary. †Information provided by author.
Sources of funding: Canadian Breast Cancer Research Alliance; Canadian Breast Cancer Research Initiative; Canadian Cancer Annual mammography vs usual care or physical breast examination only for breast cancer mortality‡ Rate per 10 000 women Mammography Usual care
At a mean 22 y RRR (95% CI) NNT (CI)
108
1% (−12 to 12)
110
Not significant
‡Abbreviations defined in Glossary. RRR, NNT, and CI calculated from control event rate and hazard ratio in article.
20 May 2014 | ACP Journal Club | Volume 160 • Number 10 Downloaded From: http://annals.org/ by a McGill University User on 11/21/2014
Society; Health and Welfare Canada; National Cancer Institute of Canada; Alberta Heritage Fund for Cancer Research; Manitoba Health Services Commission; Medical Research Council of Canada; le Ministère de la Santé et des Services Soçiaux du Québec; Nova Scotia Department of Health; Ontario Ministry of Health. For correspondence: Dr. A.B. Miller, University of Toronto, Toronto, ON, Canada. E-mail [email protected]. ■
Commentary No breast cancer screening trial has endured more angry criticism than the Canadian National Breast Screening Study (NBSS). Even for women 50 to 59 years of age, other trials found decreased breast cancer mortality with mammography screening (1). Could NBSS be wrong, or at least a statistical outlier, despite its meticulous methods? Meta-analyses have not dealt with changing breast cancer treatments. The first RCT began 51 years ago; the NBSS started in the 1980s when it became evident that adjuvant therapies (used for NBSS patients) substantially reduced mortality rates, thus potentially affecting the benefit of screening. NBSS results strengthen evidence that mammography screening leads to overdiagnosis (screen-detected cancers that would not become clinically apparent during life). After 22 years, excess numbers of invasive cancer in the mammography group represented 22% of all screen-detected cancer and 50% of nonpalpable cancer. Including ductal carcinoma in situ would raise the percentage further. No RCT has evaluated effects of new screening technologies on breast cancer mortality; ironically, these may increase overdiagnosis by finding smaller tumors. The NBSS also raises the intriguing possibility that annual standardized clinical breast examinations lasting 5 to 10 minutes— which all women age 50 to 59 years received—may be as effective as mammography for decreasing breast cancer mortality. Women and clinicians need information, even if not exact, to make informed decisions about mammography screening (2, 3). Including old RCTs, if one thousand 50-year old women have annual mammograms for the next 10 years, about 600 will have ≥ 1 false-positive mammogram, 25 will be diagnosed with invasive breast cancer (of whom 5 to 6 will be overdiagnosed and treated unnecessarily), and 3 will be “cured” (alive because of mammography). If the NBSS results are correct, the number of “cured” drops to 0. Even if the small numbers are incorrect by 100%, they can help women better understand the benefits and harms of breast cancer screening. Suzanne W. Fletcher, MD Harvard Medical School Boston, Massachusetts, USA References 1. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet. 2012; 380:1778-86. 2. Fletcher RH, Fletcher SW, Fletcher GS. Clinical Epidemiology: The Essentials, 5th edition. Philadelphia: Lippincott Williams & Wilkins. 2014 3. Welch HG, Passow HJ. Quantifying the benefits and harms of screening mammography. JAMA Intern Med. 2014;174:448-54. © 2014 American College of Physicians
JC7
