The Canadian National Breast Screening Study-1: Breast Cancer Mortality after 11 to 16 Years of Follow-up: A Randomized Screening Trial of Mammography in Women Age 40 to 49 Years

3 September 2002 | Volume 137 Issue 5 Part 1 | Pages 305-312

Background: The efficacy of breast cancer screening in women age 40 to 49 years remains controversial.

Objective: To compare breast cancer mortality in 40- to 49-year-old women who received either 1) screening with annual mammography, breast physical examination, and instruction on breast self-examination on 4 or 5 occasions or 2) community care after a single breast physical examination and instruction on breast self-examination.

Design: Individually randomized, controlled trial.

Setting: 15 Canadian centers.

Participants: 50 430 volunteers age 40 to 49 years, recruited from January 1980 to March 1985, who were not pregnant, had no previous breast cancer diagnosis, and had not had mammography in the preceding 12 months.

Interventions: Breast physical examination and instruction on breast self-examination preceded random assignment of 25 214 women to receive mammography and annual mammography, breast physical examination, and breast self-examination and 25 216 women to receive usual community care with annual follow-up.

Measurements: Verified breast cancer incidence and cohort mortality through 31 December 1993 and deaths from breast cancer through 30 June 1996.

Results: The 105 breast cancer deaths in the mammography group and 108 breast cancer deaths in the usual care group yielded a cumulative rate ratio, adjusted for mammography done outside the study, of 1.06 (95% CI, 0.80 to 1.40). A total of 592 cases of invasive breast cancer and 71 cases of in situ breast cancer were diagnosed by 31 December 1993 in the mammography group compared with 552 and 29 cases, respectively, in the usual care group. The expected proportions of nonpalpable and small invasive tumors were detected on mammography.

Conclusion: After 11 to 16 years of follow-up, four or five annual screenings with mammography, breast physical examination, and breast self-examination had not reduced breast cancer mortality compared with usual community care after a single breast physical examination and instruction on breast self-examination. The study data show that true effects of 20% or greater are unlikely.

Editors' Notes Context Seven- and 10-year results of the Canadian National Breast Screening Study (CNBSS) showed no reduction in breast cancer mortality from five annual mammographies and breast examinations for 40- to 49-year-old women. Some authors have argued that longer follow-up would reveal important benefits. Contribution After 11 to 16 years, the cumulative rate ratios for mammography versus usual care were 0.97 (95% CI, 0.74 to 1.27) for breast cancer mortality without adjustment for nonstudy mammography and 1.06 (CI, 0.80 to 1.40) with adjustment. Clinical Implications The CNBSS suggests that screening 40- to 49-year-old women is unlikely to reduce breast cancer by 20% or more. Controversy will persist because other studies suggest that screening causes small reductions in breast cancer mortality. –The Editors

 

Author and Article Information

From the University of Toronto, Toronto, Canada.

Acknowledgments: The authors thank the following CNBSS investigators for their contributions during the trial (1980 to 1988):

Center Directors: A.A. Bassett, D.C.G. Bethune, D.M. Bowman, H. Bush, J. Cantin, L. Dêschenes, J.E. Devitt, D.N. Graham, G. Hislop, A.W. Lees, B.M. Lefébvre, L. Mahoney, S.E. O'Brien, A. Simard, and W.J. Temple.

Surgeons: C.P. Armstrong, R.M. Baird, W. Beecroft, W.J. Buie, R. Bury, C.D.J. Chadwick, W.G. Chipperfield, D. Currie, G.J. Dewar, M. Falardeau, G.J. Francis, M.H. Friedman, N. Gagic, D. Girvin, H.R. Harse, D.J. Hamilton, I. Koven, U. Kuusk, R.D. Marriott, A.B. McCarten, J. McCredie, W.O. Onerheim, A. Péloquin, C. Potvin, R.E. Pow, J. Purves, P.M. Rebbeck, J. Robert, A. Robidoux, J.T. Sandy, S. Sidlofsky, E.R. Sigurdson, B. Steele, R.M. Stone, J.B. Taillefer, T.K. Thorlakson, and G.K. Thorson.

Radiologists: L. Audet, B.L. Bird, M.J. Burns, B. Capusten, W.R. Castor, G.M. Cooke, C.M. Copeland, J.W. Davidson, G.E.D. Davis, J.E.L. Desautels, R.L. Desmarais, L.A. Fried, A. Grégoire, G. Hardy, P. Hassell, G. Hébert, R. Jong, S.M. Kelly, J. Ladouceur, J. Laperrière, J.D. Longley, R.N. Ludwig, J.H.M. MacGregor, J. McCallum, J.S. Manchester, H.F. Morrish, H.A. Mueller, T. Minuk, D. Ouimet-Oliva, P. Poon, O. Prosmanne, P. Rasuli, N.L. Patt, M. Petitclerc, J.W. Radomsky, J.L. Robillard, I.S. Simor, R.K. Sparrow, B.J. Shapiro, S.L. Share, H.K. Standing, W.J. Weiser, and A.H. Zalev.

Pathologists: F. Alexander, Y. Boivin, N. Cooter, J. Danyluk, D. Dawson, T.J. D'Souza, M. Jabi, S. Jacob, J. Safneck, W. Schurch, H. Strawbridge, D.I. Turnbull, R. Vauclair, A. Worth, H. Yazdi, and I. Zayid.

Reference Radiologist: D.V. McFarlane.

Reference Physicist: M. Yaffe.

The authors also thank the women who volunteered to participate in this trial and who willingly gave of their time and energy, knowing it was an experiment but doing so for the benefit of all women.

They thank Catherine Andrew (formerly the CNBSS quality control supervisor), who followed up breast cancer cases from the national office of the trial, for her many years of dedication to the trial.

They also thank the staff of the coordinating and local centers in the trial, not specifically mentioned as authors of this paper, in particular Charlotte Turnbull, the national coordinator, and the local coordinators in the centers: Luby Carr, Bette Johnston, Ann Hampson, Carrol Clarkson (Mt. Sinai, Toronto, Ontario); Andrée Christen (Québec); Chantal Perret, Lise Simard (Hôpital Notre-Dame, Montréal, Québec); Joan Alvarez, Margaret Opie (Hamilton, Ontario); Pat Edward (Winnipeg, Manitoba); Margaret Fryer (Vancouver, British Columbia); Judy Snider (Ottawa, Ontario); Lorraine Grégoire (Hôpital Hôtel-Dieu, Montréal, Québec); L'ainée Duncan (Halifax, Nova Scotia); Donna Dean, Maureen Campbell (London, Ontario); Carol May (Edmonton, Alberta); Kay Johnson (Red Deer, Alberta); Louise Watson (Calgary, Alberta); Pat Carpick (St. Michaels, Toronto, Ontario).

The authors thank the nurses and radiographers, whose skills contributed to the validity of the screening tests, and the secretaries, telephone callers, coders, data entry personnel, and programmers, who all contributed to the success of the trial.

A particular acknowledgement is due the volunteers who contributed their time and energy at many of the screening centers. Special tribute is made to the memory of Shiela Netton, who had bilateral breast cancer diagnosed before the beginning of the study. She contributed much to the recruitment of the initial volunteers in Toronto but died of her disease before the study was concluded.

Grant Support: CNBSS-1 was funded by the Canadian Cancer Society, the Department of National Health and Welfare, the National Cancer Institute of Canada, the Alberta Heritage Fund for Cancer Research, the Manitoba Health Services Commission, the Medical Research Council of Canada, le Ministere de la Sante et des Service Sociaux du Québec, the Nova Scotia Department of Health, and the Ontario Ministry of Health. More recently, the follow-up has been supported by the Canadian Breast Cancer Research Initiative. Dr. Miller was supported in part by a National Health Scientist Award from the Department of National Health and Welfare of Canada.

Requests for Single Reprints: Anthony B. Miller, MB, FRCP, Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, im Neuenheimer Feld 280, D-69120 Heidelberg, Germany; e-mail, a.miller{at}dkfz-heidelberg.de.

Current Author Addresses: Dr. Miller: Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.

Dr. To: Population Health Sciences, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.

Dr. Baines: Department of Public Health Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

Mr. Wall: Institute of Clinical Evaluative Sciences of Ontario, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.

Author Contributions: Conception and design: A.B. Miller.

Analysis and interpretation of the data: A.B. Miller, T. To, C.J. Baines.

Drafting of the article: A.B. Miller, C.J. Baines.

Critical revision of the article for important intellectual conent: A.B. Miller, C.B. Baines.

Final approval of the article: A.B. Miller, C.J. Baines.

Obtaining of funding: A.B. Miller.

Collection and assembly of data: A.B. Miller, T. To, C.J. Baines, C. Wall.