The
Canadian
National
Breast
Screening Study:
Te Canadian National Breast Screening Sudy: a clinician's perspective
Adalei A. Starreveld, MD, FRCPC
ncologists who devote all or most of their practice to patients with breast cancer witness firsthand the effect mammography has on women's lives. They also witness the impact of publicity that follows on the heels of preliminary reports at medical meetings. One may question the naivete with which stones of great weight are thrown in the public pond. A young woman, who during high school had lost her mother to breast cancer, made clear to me how we trust technology much more than our fingers. She had felt a small, hard lump high in the upper outer quadrant of her left breast. When she underwent mammography, she was aware that it was being performed just at the edge of the lump. Her desire to hear good news was so great that she did not question the family physician's report of normal results and took further action only when the lump was twice as large, 2 montlis later. We all like to hear good news. We expected the Canadian National Breast Screening Study (NBSS) to clarify the controversial findings on screening of women aged 40 to 49 years (see page 1459) and to confirm the benefit of screening by mammography in women aged 50 to 59 years (see page 1477). The Health Insurance Plan of Greater New York,' in a controlled prospective trial conducted in the 1 960s, established that annual screening by mammography combined with physical examination of the breasts reduced the risk of death from breast cancer. This trial was followed by several others, but because of differences in protocol among the studies, the findings are difficult to compare. It has become generally accepted, however, that screening by mammography, preferably combined with physical examination of the breasts, reduces the risk of death from breast cancer by 25% to 40% among women aged 50 years or more. No studies have demonstrated convincingly that younger women benefit from screening by mammography, at least not in the first 7 to 10 years after O
screening. In the United States, screening practices have been strongly influenced by the findings of the Breast Cancer Detection Demonstration Project,2 a nonrandomized study conducted between 1973 and 1981 that involved more than 250 000 women. Examining the results of five randomized studies involving women aged 40 to 49 years Day and Duffy3 noted that the groups undergoing mammographic screening had a 5% lower rate of death from breast cancer overall and the following individual differences: Health Insurance Plan of Greater New York study, 24% lower; Swedish two-county study, 6% lower; Edinburgh study, 2% greater; Stockholm study, 7% greater; and Malmo study, 29% greater. After 7 years the NBSS has found that combined screening by mammography and physical examination does not reduce the rate of death from breast cancer in women aged 40 to 49 years and therefore seems to be of no value. There was in fact a 36% greater rate (not significant) in the screened group compared with the control group. In women aged 50 to 59 years annual mammography added to physical examination provided no further benefit. Both younger and older women with cancers diagnosed by mammography alone lived longer, although the overall rate of death from breast cancer has not yet fallen. Some of these results are not consistent with the previously mentioned findings. When faced with counterintuitive results, one is inclined to disbelieve them or to suspect that things beyond the control of the investigators went wrong. However, the NBSS was designed not to test mammography but to screen asymptomatic women for breast cancer. If we accept the study results at their face value we have to conclude that women aged 40 to 49 years do not benefit from mammography or physical examination and that women aged 50 to 59 years do not have increased benefit with mammography, although in screens 2 to 5 combining mammography and physical examination improved survival somewhat (not quite significantly). The very high
Dr. Starreveld is professor, Department ofRadiology and Diagnostic Imaging, University ofAlberta, Edmonton, and a radiation oncologist at the Cross Cancer Institute, Edmonton, Alta.
Reprint requests to: Dr. Adalei A. Starreveld, Department ofRadiation Oncology, Cross Cancer Institute, 11560 University Ave., Edmonton, AB TSJ IZ2 -
For prescribing information see page 1589
CAN MED ASSOC J
1992; 147 (IO)
1437
survival rate for women aged 50 to 59 years 7 years after mammography and physical examination in screens 2 to 5 (95%) in comparison with the 7-year survival rate for patients registered with breast cancer in northern Alberta between 1980 and 1984 (68.5%) (unpublished data) raises serious doubts about the completeness of the NBSS mortality data. The increased detection rate with screening by physical examination alone is not statistically significant: the ratio of observed to expected incidence rates of invasive breast cancer in women aged 50 to 59 years is just 1.18 (95% confidence interval [CI] 0.96 to 1.45). Interestingly, the ratio for women who underwent mammography and physical examination, 1.28 (95% CI 1.05 to 1.56), is statistically significant, consistent with the slightly increased survival rate. What could have gone wrong? To their credit, the investigators arranged for thorough quality assessment throughout the study and published the results of their audits on the role of the nurseexaminer,4 physical examination by nurses and (Quebec) physicians,5 the role of the reference radiologist6 and the results of mammography.7-9 Serious criticism has been voiced about the last item,'0-'2 and concerns remain about the quality of mammography in the participating centres, especially during the first few years of the study. The use of mammography to find small cancers is undisputed, and the survival rates of patients with very small cancers, even when poorly differentiated, suggest cure, a concept infrequently and hesitantly mentioned in the breast-cancer literature. Tabar and associates'3 '4 and Tubiana and Koscielny's gave compelling evidence not only for the cure of small breast cancers but also for a declining degree of differentiation with increasing tumour size. Tabar and associates' latest analysis of the Swedish two-county program'4 offers guidelines for the quantification of desirable results of screening by mammography. It suggests that more than 50% of cancers detected by screening should be less than 15 mm in diameter. In the NBSS 51% of the cancers detected at screen 1 by mammography and physical examination in women aged 40 to 49 years and 50% of those in women aged 50 to 59 were less than 20 mm in diameter. The Swedish paper also suggests that more than 70% of women with tumours so detected should be free of node involvement. Among the women aged 40 to 49 years in the NBSS the rates were 61% for those with tumours detected in the first screening and 71% for those with tumours detected by subsequent screening; among the women aged 50 to 59 years the rate was 71% for both categories. Another suggestion is that the detection rate at the first screening should be at least three times the expected incidence rate without screening. The ratio 1438
CAN MED ASSOCJ 1992; 147 (10)
of observed cancers in the first year in the NBSS women aged 40 to 49 years to expected cancers in women in the same age group (Statistics Canada data) was 3.2, and the observed to expected ratio in women aged 50 to 59 years was 3.6. The expected rates are for the general population and should be adjusted for the NBSS sample, which appears to have had more risk factors for breast cancer. Not all the risk variables included in the prerandomization questionnairel6 are listed in the final report; it might be possible, with Gail and collaborators' model,"7 to establish a composite risk profile for the NBSS sample. Other criteria suggested by Tabar and associates'4 pertain to proportions of grade 3 cancers among those of a given size. The degree of differentiation of the cancers diagnosed in the NBSS is not available. All slides appear to have been reviewed by an NBSS pathologist, so complete data on degree of differentiation and size might be possible. No matter how the speed of growth of breast cancers has been estimated, from serial mammograms,'8 from the interval between radical mastectomy and chest-wall recurrence,'9 from observations by the patient or the physician, or both, as in "auxometry, "20 or from other methods,2' 22 the overall conclusion is that younger women tend to have cancers with short doubling times, often only a few months. Frierson23 stated that in five of eight reports in which the S-phase fraction of breast cancers (the proportion of cells that synthesize DNA, as a measure of proliferative activity of the cancer) was compared with the age of the patient, younger women (less than 50 years old) more often had tumours with high S-phase fraction values. Younger women with fast-growing tumours should be a challenge: too long an interval between screenings will result in these cancers being missed, as will less-thanoptimal mammography. Negative results of screening, by imparting a false sense of security, may cause delay, which could worsen the prognosis of a woman with a fast-growing cancer.24 It remains to be seen whether mammography can be beneficial to younger women. We may have to wait until a radiologic technique, such as magnetic resonance imaging,25 with greater resolution and without carcinogenic properties, becomes useful in screening for breast cancer.
References 1. Shapiro S, Venet W, Strax P et al: Current results of the breast cancer screening randomized trial: the Health Insurance Plan (HIP) of Greater New York study [chap 6]. In Day NE, Miller AB (eds): Screening for Breast Cancer, Huber, Toronto, 1988 2. Baker LH: Breast Cancer Detection Demonstration Project: five-year summary report. CA Cancer J C/in 1982; 32: 194LE 15 NOVEMBRE 1992
225 3. Day NE, Duffy SW: Breast screening in women under 50 [C]. Lancet 1991; 338: 113-114 4. Miller AB, Baines CJ, Turnbull C: The role of the nurseexaminer in the National Breast Screening Study. Can J Public Health 1991; 82: 162-167 5. Baines CJ, Miller AB, Bassett AA: Physical examination. Its role as a single screening modality in the Canadian National Breast Screening Study. Cancer 1989; 63: 1816-1822 6. Baines CJ, McFarlane DV, Miller AB: The role of the reference radiologist. Estimates of inter-observer agreement and potential delay in cancer detection in the National Breast Screening Study. Invest Radiol 1990; 25: 971-976 7. Baines CJ, Miller AB, Wall C et al: Sensitivity and specificity of first screen mammography in the Canadian National Breast Screening Study: a preliminary report from five centers. Radiology 1986; 160: 295-298 8. Baines CJ, McFarlane DV, Wgll C: Audit procedures in the National Breast Screening Study: mammography interpretation. Can Assoc Radiol J 1986; 37: 256-260 9. Baines CJ, Miller AB, Kopans DB et al: Canadian National Breast Screening Study: assessment of technical quality by external review. AJR 1990; 155: 743-747 10. Breast cancer screening in women under 50 [E]. Lancet 1991; 337: 1575-1576 11. Kopans DB: Breast screening in women under 50. Lancet 1991; 338:447 12. Kopans DB: The Canadian screening program: a different perspective. AJR 1990; 155: 748-749 13. Tabar L, Fagerberg G, Day NE et al: Breast cancer treatment and natural history: new insights from results of screening. Lancet 1992; 339: 412-414 14. Tabar L, Fagerberg G, Duffy SW et al: Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am 1992; 30: 187-210 15. Tubiana M, Koscielny S: Natural history of human breast cancer: recent data and clinical implications. Breast Cancer Res Treat 1991; 18: 125-140 16. Miller AB, Howe GR, Wall C: The National Study of Breast Cancer Screening: protocol for a Canadian randomized controlled trial of screening for breast cancer in women. Clin Invest Med 1981; 4: 227-258 17. Gail MH, Brinton LA, Byar DP et al: Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989; 81: 1879-1886 18. Gershon-Cohen J, Berger SN, Klickstein HS: Roentgenography of breast cancer moderating concept of biologic predeterminism. Cancer 1963; 16: 961-967 19. Pearlman AW: Breast cancer - influence of growth rate on prognosis and treatment evaluation. A study based on mastectomy scar recurrences. Cancer 1976; 38: 1826-1833 20. Charlson ME, Feinstein AR: The auxometric dimension. A new method for using rate of growth in prognostic staging of breast cancer. JAMA 1974; 228: 180-185 21. Kuroishi T, Tominaga S, Morimoto T et al: Tumor growth rate and prognosis of breast cancer mainly detected by mass screening. Jpn J Cancer Res 1990; 81: 454-462 22. Kusama S, Spratt JS, Donegan WL et al: The gross rates of growth of human mammary carcinoma. Cancer 1972; 30: 594-599 23. Frierson HF: Ploidy analysis and S-phase fraction determination by flow cytometry of invasive adenocarcinomas of the breast. Am J Surg Pathol 1991; 15: 358-367 24. Moskowitz M: Guidelines for screening for breast cancer. Is a revision in order? Radiol Clin North Am 1992; 30: 221-233 25. Wehrli FW: The origins and future of nuclear magnetic resonance imaging. What began as a curiosity of physics has become the preeminent method of diagnostic medical imaging and may displace x-ray-based techniques in the 21st century. Physics Today 1992; June: 34-42 NOVEMBER 15, 1992
Conferences continued from page 1429 126th Annual Meeting of the Canadian Medical Association * 126e Assemblee generale annuelle de l'Association medicale canadienne Aug. 22-26, 1993 / du 22 au 26 aouit 1993 Skyline Plaza Hotel and Calgary Convention Centre, Calgary 127th Annual Meeting of the Canadian Medical Association * 127e Assemblee generale annuelle de l'Association medicale canadienne Aug. 14-19, 1994 / du 14 au 19 aouit 1994 Montreal CMA Meetings and Travel Department / Departement des conferences et voyages de I'AMC, PO Box/CP 8650, Ottawa, ON KIG OG8; tel (613) 731-9331 or/ou (800) 267-9703, fax (613) 523-0937
Other Conferences * Conferences diverses Dec. 17, 1992: Beyond Survival - Caring for Ourselves (part 9 of 9 in the Women Healing from Childhood Trauma Workshop Series) Toronto Registration coordinator, Community Resources and Initiatives, 106-344 Dupont St., Toronto, ON M5R IV9; tel (416) 924-8998, fax (416) 924-8352 Du 20 au 23 dec. 1992: Congres francophone de sexologie, fertilite et infectiologie (organise par la Societe marocaine de fertilite et de contraception [SMFC]) Marrakech, Morocco Secretariat du congres, SMFC, 143, rue Prince Moulay Abdellah, BP Casa principale 15851, Casablanca, Morocco; tel 011-212-2-26-29-59, fax 011-212-226-28-94 Jan. 10-12, 1993: 3rd Primary Care Research Conference: "Challenges in Practice-Based Research" Atlanta Third Primary Care Research Conference, Ste. 410, N Tower, 7315 Wisconsin Ave., Bethesda, MD 20814; tel (301) 229-3002, fax (301) 229-9553 Jan. 10-15, 1993: World Congress on Tourist Medicine and Health (organized by the National University of
Singapore, the Ministry of the Environment, Singapore, the Singapore Convention Bureau and the World Health Organization Collaborating Centre for Tourist Health and Tourist Medicine)
Singapore Secretariat, World Congress on Tourist Medicine and Health, 336 Smith St., No. 06-302, New Bridge Centre,
Singapore 0105, Republic of Singapore; tel 011-65227-9811, fax 011-65-227-0257
continued on page 1445 CAN MED ASSOC J 1992; 147 (10)
1439
Canadian
National
Breast
Screening Study:
Te Canadian National Breast Screening Sudy: a clinician's perspective
Adalei A. Starreveld, MD, FRCPC
ncologists who devote all or most of their practice to patients with breast cancer witness firsthand the effect mammography has on women's lives. They also witness the impact of publicity that follows on the heels of preliminary reports at medical meetings. One may question the naivete with which stones of great weight are thrown in the public pond. A young woman, who during high school had lost her mother to breast cancer, made clear to me how we trust technology much more than our fingers. She had felt a small, hard lump high in the upper outer quadrant of her left breast. When she underwent mammography, she was aware that it was being performed just at the edge of the lump. Her desire to hear good news was so great that she did not question the family physician's report of normal results and took further action only when the lump was twice as large, 2 montlis later. We all like to hear good news. We expected the Canadian National Breast Screening Study (NBSS) to clarify the controversial findings on screening of women aged 40 to 49 years (see page 1459) and to confirm the benefit of screening by mammography in women aged 50 to 59 years (see page 1477). The Health Insurance Plan of Greater New York,' in a controlled prospective trial conducted in the 1 960s, established that annual screening by mammography combined with physical examination of the breasts reduced the risk of death from breast cancer. This trial was followed by several others, but because of differences in protocol among the studies, the findings are difficult to compare. It has become generally accepted, however, that screening by mammography, preferably combined with physical examination of the breasts, reduces the risk of death from breast cancer by 25% to 40% among women aged 50 years or more. No studies have demonstrated convincingly that younger women benefit from screening by mammography, at least not in the first 7 to 10 years after O
screening. In the United States, screening practices have been strongly influenced by the findings of the Breast Cancer Detection Demonstration Project,2 a nonrandomized study conducted between 1973 and 1981 that involved more than 250 000 women. Examining the results of five randomized studies involving women aged 40 to 49 years Day and Duffy3 noted that the groups undergoing mammographic screening had a 5% lower rate of death from breast cancer overall and the following individual differences: Health Insurance Plan of Greater New York study, 24% lower; Swedish two-county study, 6% lower; Edinburgh study, 2% greater; Stockholm study, 7% greater; and Malmo study, 29% greater. After 7 years the NBSS has found that combined screening by mammography and physical examination does not reduce the rate of death from breast cancer in women aged 40 to 49 years and therefore seems to be of no value. There was in fact a 36% greater rate (not significant) in the screened group compared with the control group. In women aged 50 to 59 years annual mammography added to physical examination provided no further benefit. Both younger and older women with cancers diagnosed by mammography alone lived longer, although the overall rate of death from breast cancer has not yet fallen. Some of these results are not consistent with the previously mentioned findings. When faced with counterintuitive results, one is inclined to disbelieve them or to suspect that things beyond the control of the investigators went wrong. However, the NBSS was designed not to test mammography but to screen asymptomatic women for breast cancer. If we accept the study results at their face value we have to conclude that women aged 40 to 49 years do not benefit from mammography or physical examination and that women aged 50 to 59 years do not have increased benefit with mammography, although in screens 2 to 5 combining mammography and physical examination improved survival somewhat (not quite significantly). The very high
Dr. Starreveld is professor, Department ofRadiology and Diagnostic Imaging, University ofAlberta, Edmonton, and a radiation oncologist at the Cross Cancer Institute, Edmonton, Alta.
Reprint requests to: Dr. Adalei A. Starreveld, Department ofRadiation Oncology, Cross Cancer Institute, 11560 University Ave., Edmonton, AB TSJ IZ2 -
For prescribing information see page 1589
CAN MED ASSOC J
1992; 147 (IO)
1437
survival rate for women aged 50 to 59 years 7 years after mammography and physical examination in screens 2 to 5 (95%) in comparison with the 7-year survival rate for patients registered with breast cancer in northern Alberta between 1980 and 1984 (68.5%) (unpublished data) raises serious doubts about the completeness of the NBSS mortality data. The increased detection rate with screening by physical examination alone is not statistically significant: the ratio of observed to expected incidence rates of invasive breast cancer in women aged 50 to 59 years is just 1.18 (95% confidence interval [CI] 0.96 to 1.45). Interestingly, the ratio for women who underwent mammography and physical examination, 1.28 (95% CI 1.05 to 1.56), is statistically significant, consistent with the slightly increased survival rate. What could have gone wrong? To their credit, the investigators arranged for thorough quality assessment throughout the study and published the results of their audits on the role of the nurseexaminer,4 physical examination by nurses and (Quebec) physicians,5 the role of the reference radiologist6 and the results of mammography.7-9 Serious criticism has been voiced about the last item,'0-'2 and concerns remain about the quality of mammography in the participating centres, especially during the first few years of the study. The use of mammography to find small cancers is undisputed, and the survival rates of patients with very small cancers, even when poorly differentiated, suggest cure, a concept infrequently and hesitantly mentioned in the breast-cancer literature. Tabar and associates'3 '4 and Tubiana and Koscielny's gave compelling evidence not only for the cure of small breast cancers but also for a declining degree of differentiation with increasing tumour size. Tabar and associates' latest analysis of the Swedish two-county program'4 offers guidelines for the quantification of desirable results of screening by mammography. It suggests that more than 50% of cancers detected by screening should be less than 15 mm in diameter. In the NBSS 51% of the cancers detected at screen 1 by mammography and physical examination in women aged 40 to 49 years and 50% of those in women aged 50 to 59 were less than 20 mm in diameter. The Swedish paper also suggests that more than 70% of women with tumours so detected should be free of node involvement. Among the women aged 40 to 49 years in the NBSS the rates were 61% for those with tumours detected in the first screening and 71% for those with tumours detected by subsequent screening; among the women aged 50 to 59 years the rate was 71% for both categories. Another suggestion is that the detection rate at the first screening should be at least three times the expected incidence rate without screening. The ratio 1438
CAN MED ASSOCJ 1992; 147 (10)
of observed cancers in the first year in the NBSS women aged 40 to 49 years to expected cancers in women in the same age group (Statistics Canada data) was 3.2, and the observed to expected ratio in women aged 50 to 59 years was 3.6. The expected rates are for the general population and should be adjusted for the NBSS sample, which appears to have had more risk factors for breast cancer. Not all the risk variables included in the prerandomization questionnairel6 are listed in the final report; it might be possible, with Gail and collaborators' model,"7 to establish a composite risk profile for the NBSS sample. Other criteria suggested by Tabar and associates'4 pertain to proportions of grade 3 cancers among those of a given size. The degree of differentiation of the cancers diagnosed in the NBSS is not available. All slides appear to have been reviewed by an NBSS pathologist, so complete data on degree of differentiation and size might be possible. No matter how the speed of growth of breast cancers has been estimated, from serial mammograms,'8 from the interval between radical mastectomy and chest-wall recurrence,'9 from observations by the patient or the physician, or both, as in "auxometry, "20 or from other methods,2' 22 the overall conclusion is that younger women tend to have cancers with short doubling times, often only a few months. Frierson23 stated that in five of eight reports in which the S-phase fraction of breast cancers (the proportion of cells that synthesize DNA, as a measure of proliferative activity of the cancer) was compared with the age of the patient, younger women (less than 50 years old) more often had tumours with high S-phase fraction values. Younger women with fast-growing tumours should be a challenge: too long an interval between screenings will result in these cancers being missed, as will less-thanoptimal mammography. Negative results of screening, by imparting a false sense of security, may cause delay, which could worsen the prognosis of a woman with a fast-growing cancer.24 It remains to be seen whether mammography can be beneficial to younger women. We may have to wait until a radiologic technique, such as magnetic resonance imaging,25 with greater resolution and without carcinogenic properties, becomes useful in screening for breast cancer.
References 1. Shapiro S, Venet W, Strax P et al: Current results of the breast cancer screening randomized trial: the Health Insurance Plan (HIP) of Greater New York study [chap 6]. In Day NE, Miller AB (eds): Screening for Breast Cancer, Huber, Toronto, 1988 2. Baker LH: Breast Cancer Detection Demonstration Project: five-year summary report. CA Cancer J C/in 1982; 32: 194LE 15 NOVEMBRE 1992
225 3. Day NE, Duffy SW: Breast screening in women under 50 [C]. Lancet 1991; 338: 113-114 4. Miller AB, Baines CJ, Turnbull C: The role of the nurseexaminer in the National Breast Screening Study. Can J Public Health 1991; 82: 162-167 5. Baines CJ, Miller AB, Bassett AA: Physical examination. Its role as a single screening modality in the Canadian National Breast Screening Study. Cancer 1989; 63: 1816-1822 6. Baines CJ, McFarlane DV, Miller AB: The role of the reference radiologist. Estimates of inter-observer agreement and potential delay in cancer detection in the National Breast Screening Study. Invest Radiol 1990; 25: 971-976 7. Baines CJ, Miller AB, Wall C et al: Sensitivity and specificity of first screen mammography in the Canadian National Breast Screening Study: a preliminary report from five centers. Radiology 1986; 160: 295-298 8. Baines CJ, McFarlane DV, Wgll C: Audit procedures in the National Breast Screening Study: mammography interpretation. Can Assoc Radiol J 1986; 37: 256-260 9. Baines CJ, Miller AB, Kopans DB et al: Canadian National Breast Screening Study: assessment of technical quality by external review. AJR 1990; 155: 743-747 10. Breast cancer screening in women under 50 [E]. Lancet 1991; 337: 1575-1576 11. Kopans DB: Breast screening in women under 50. Lancet 1991; 338:447 12. Kopans DB: The Canadian screening program: a different perspective. AJR 1990; 155: 748-749 13. Tabar L, Fagerberg G, Day NE et al: Breast cancer treatment and natural history: new insights from results of screening. Lancet 1992; 339: 412-414 14. Tabar L, Fagerberg G, Duffy SW et al: Update of the Swedish two-county program of mammographic screening for breast cancer. Radiol Clin North Am 1992; 30: 187-210 15. Tubiana M, Koscielny S: Natural history of human breast cancer: recent data and clinical implications. Breast Cancer Res Treat 1991; 18: 125-140 16. Miller AB, Howe GR, Wall C: The National Study of Breast Cancer Screening: protocol for a Canadian randomized controlled trial of screening for breast cancer in women. Clin Invest Med 1981; 4: 227-258 17. Gail MH, Brinton LA, Byar DP et al: Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 1989; 81: 1879-1886 18. Gershon-Cohen J, Berger SN, Klickstein HS: Roentgenography of breast cancer moderating concept of biologic predeterminism. Cancer 1963; 16: 961-967 19. Pearlman AW: Breast cancer - influence of growth rate on prognosis and treatment evaluation. A study based on mastectomy scar recurrences. Cancer 1976; 38: 1826-1833 20. Charlson ME, Feinstein AR: The auxometric dimension. A new method for using rate of growth in prognostic staging of breast cancer. JAMA 1974; 228: 180-185 21. Kuroishi T, Tominaga S, Morimoto T et al: Tumor growth rate and prognosis of breast cancer mainly detected by mass screening. Jpn J Cancer Res 1990; 81: 454-462 22. Kusama S, Spratt JS, Donegan WL et al: The gross rates of growth of human mammary carcinoma. Cancer 1972; 30: 594-599 23. Frierson HF: Ploidy analysis and S-phase fraction determination by flow cytometry of invasive adenocarcinomas of the breast. Am J Surg Pathol 1991; 15: 358-367 24. Moskowitz M: Guidelines for screening for breast cancer. Is a revision in order? Radiol Clin North Am 1992; 30: 221-233 25. Wehrli FW: The origins and future of nuclear magnetic resonance imaging. What began as a curiosity of physics has become the preeminent method of diagnostic medical imaging and may displace x-ray-based techniques in the 21st century. Physics Today 1992; June: 34-42 NOVEMBER 15, 1992
Conferences continued from page 1429 126th Annual Meeting of the Canadian Medical Association * 126e Assemblee generale annuelle de l'Association medicale canadienne Aug. 22-26, 1993 / du 22 au 26 aouit 1993 Skyline Plaza Hotel and Calgary Convention Centre, Calgary 127th Annual Meeting of the Canadian Medical Association * 127e Assemblee generale annuelle de l'Association medicale canadienne Aug. 14-19, 1994 / du 14 au 19 aouit 1994 Montreal CMA Meetings and Travel Department / Departement des conferences et voyages de I'AMC, PO Box/CP 8650, Ottawa, ON KIG OG8; tel (613) 731-9331 or/ou (800) 267-9703, fax (613) 523-0937
Other Conferences * Conferences diverses Dec. 17, 1992: Beyond Survival - Caring for Ourselves (part 9 of 9 in the Women Healing from Childhood Trauma Workshop Series) Toronto Registration coordinator, Community Resources and Initiatives, 106-344 Dupont St., Toronto, ON M5R IV9; tel (416) 924-8998, fax (416) 924-8352 Du 20 au 23 dec. 1992: Congres francophone de sexologie, fertilite et infectiologie (organise par la Societe marocaine de fertilite et de contraception [SMFC]) Marrakech, Morocco Secretariat du congres, SMFC, 143, rue Prince Moulay Abdellah, BP Casa principale 15851, Casablanca, Morocco; tel 011-212-2-26-29-59, fax 011-212-226-28-94 Jan. 10-12, 1993: 3rd Primary Care Research Conference: "Challenges in Practice-Based Research" Atlanta Third Primary Care Research Conference, Ste. 410, N Tower, 7315 Wisconsin Ave., Bethesda, MD 20814; tel (301) 229-3002, fax (301) 229-9553 Jan. 10-15, 1993: World Congress on Tourist Medicine and Health (organized by the National University of
Singapore, the Ministry of the Environment, Singapore, the Singapore Convention Bureau and the World Health Organization Collaborating Centre for Tourist Health and Tourist Medicine)
Singapore Secretariat, World Congress on Tourist Medicine and Health, 336 Smith St., No. 06-302, New Bridge Centre,
Singapore 0105, Republic of Singapore; tel 011-65227-9811, fax 011-65-227-0257
continued on page 1445 CAN MED ASSOC J 1992; 147 (10)
1439
