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MAMMOGRAPHY IN SYMPTOMATIC BREAST DISEASE
887 TABLE I-PRESENTING SYMPTOMS OR REASON FOR
Hospital Practice
MAMMOGRAPHY IN
4518
562 PATIENTS WITH BREAST CANCER AND WITH BENIGN CONDITIONS
MAMMOGRAPHY IN SYMPTOMATIC BREAST DISEASE A. R. MANHIRE A. P. LOCKER VERDI STICKLAND JENNIFER CASELDINE R. W. BLAMEY
Department of Surgery, City Hospital, Nottingham NG5 1PB The contribution of mammography to the diagnosis of breast cancer was examined in 5080 patients with various breast symptoms. There were 562 breast cancers within this group. The sensitivity of mammography was 88%. Only 18 cancers were detected by mammography alone, and of these 3 were in the other breast. 7 of the remaining 15 cancers had clinical signs which would have been pursued to open biopsy in the absence of mammography. Clinical examination is of paramount importance in the management of patients with symptomatic breast disease. Mammography is most useful when applied in specific situations rather than to screen every patient with breast symptoms.
Summary
INTRODUCTION
EXAMINATION of the breast by mammography has become widely practised over the past 25 years, and a national mammographic breast screening programme1 has been introduced in the UK. Mammography is the method of choice for screening symptom-free women over 50 years of age but its value in the investigation of symptomatic breast disease is less well defined. If we wish to use mammography to investigate patients who present with symptoms we need to know whether a significant proportion of clinically occult breast cancers will be detected by this method. Furthermore the false-negative rate should not be high. Our aim was to evaluate the contribution of mammography in women presenting with various symptoms of breast disease, and to better defme the most effective use of mammographic facilities. MATERIALS AND METHODS
Since 1973 the breast unit at the City Hospital, Nottingham, has increasing numbers of women with various breast symptoms referred by general practitioners. There are now about 3000 new referrals a year. At the initial outpatient attendance, all patients were examined clinically by a senior member of the breast unit team. Biopsies were seen
10.
Morstyn G, Souza LM, Keech J, et al Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy Lancet 1988; i 667-72. 11. Gabrilove JL, Jakubowski A, Scher H, et al. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med 1988; 318: 1414-22. 12. Duhrsen U, Villeval J-L, Boyd J, et al. Effects of recombinant human granulocyte colony-stimulating factor on hemopoietic progenitor cells in cancer patients Blood 1988, 72: 2074-81. 13. Vadhan-Raj S, Buescher S, Broxmeyer HE, et al, Stimulation of myelopoiesis in patients with aplastic anemia by recombinant human granulocyte-macrophage colony-stimulating factor. N Engl JMed 1988; 319: 1628-34. 14 Groopman JE, Mitsuyasu RT, De Leo MJ, et al Effects of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 1987; 317: 593-98. 15 Brandt SJ, Peters WP, Atwater SK, et al. Effect of recombinant human granulocytemacrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N EnglJ Med 1988; 318: 869-76.
*Single duct. tMulti or single duct. done only on discrete breast lumps; where there were areas of thickening within the breast the patient was reassessed at the other phase of her menstrual cycle. Biopsies were generally done by ’Tru-cut’ needle but lately fme-needle aspiration cytology has been used. Referral for
mammography was at the discretion of the examining clinician; only patients under 30 years of age were specifically excluded. Biopsy was always done when a breast lump had been detected clinically but the mammogram was normal. Conversely, all patients with mammographic abnormalities were followed up or biopsies done if the examiner was worried. From our breast clinic records, we determined the main presenting symptom in all patients referred by their general practitioner between Jan 1, 1981 and Dec 31, 1987. Within this group the patients diagnosed as having breast cancer were identified, and we noted whether a breast lump was recorded as present on initial examination. We regarded a lump as present only if it had been recorded in diagrammatic or written form in the case notes or if the patient had undergone needle or excisional biopsy. The mammograms from all the patients with proven breast cancer were reviewed by one radiologist (A. R. M.) who was aware of the diagnosis in each case. Mammograms were classified as positive or negative for malignancy for each of the two projections (craniocaudal and 45’oblique), or as indeterminate if the films were difficult to interpret. RESULTS
In the
study period a total of 5080 patients with symptomatic breast disease had mammography at the City Hospital. 562 of these were diagnosed histologically as having invasive (545, 97%) or in-situ (17, 3%) breast cancers. The median age of the 562 patients was 54 years (range 30-78). 163 patients (29%) were aged 50 or less. The median age of the 4518 patients with benign conditions was J, Singer JW, Buckner CD, et al Use of recombinant human granulocyte-macrophage colony-stimulating factors in autologous marrow transplantanon for lymphoid malignancies. Blood 1988; 72: 834-36. 17. Vadhan-Raj S, Keating M, Le Maistre A, et al. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes N Engl J Med 1987; 317: 1545-52. 18. Antin JH, Smith BR, Holmes W, Rosenthal DS. Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome. Blood 1988; 72: 705-13. 19. Metcalf D. The molecular control of blood cells Boston Harvard University Press, 16. Nemunaitis
1988.
Begley CG, Metcalf D, Nicola NA Purified colony stimulating factors (G-CSF and GM-CSF) induce differentiation in HL60 leukemic cells with suppression of cloneogenicity. Int J Cancer 1987; 39: 99-105. 21. Metcalf D, Hilton DJ, Nicola NA. Clonal analysis of the actions of the murine leukemia inhibitory factor on leukemic and normal munne hemopoietic cells.
20.
Leukemia 1988, 2: 216-21. TM, Justement J, Kinter A, et al. Cytokine-induced expression of HIV-1in chronically infected promonocytic cell line. Science 1987; 238: 800-02.
22. Folks
a
888 TABLE II-RESULTS OF MAMMOGRAPHY IN
562
PATIENTS WITH
BREAST CANCER
d’orange, and a hard axillary gland. Thus, there were 8 patients in whom a carcinoma was present in the symptomatic breast with no clinical finding which would
biopsy. These patients had a median age of 565 years (range 37-68).
have led to
DISCUSSION
47 years
(range 30 to 74). Overall, in benign and malignant categories, 2908 (57%) women were under 50 years old. 12 patients had synchronous bilateral breast cancer, which we have defined as cancer detected in the other breast diagnosis or within three months. In 9 of these patients, both carcinomas were palpable. In the remaining 3 the cancer in the other breast was detected by mammography. Table I shows the principal presenting symptom in the 562 patients with breast cancer and the 4518 with benign conditions. 72% of the cancers were diagnosed by tru-cut needle biopsy; 6% had fine-needle aspiration cytology only, and in 21 % an excisional biopsy was needed, usually because the tru-cut biopsy specimen was inadequate or benign. Occasionally the lump was too small for needle biopsy. In 9 (1-6%) patients Paget’s disease was diagnosed at
by nipple biopsy. Table n shows the results of the radiologist’s review of the mammograms. If we include the indeterminate category as positive for breast cancer the sensitivity of mammography in the detection of known cancers is 87-9%. Thus 68 (12%) patients had no mammographic evidence of breast cancer, the diagnosis being made solely by clinical examination and
biopsy. In only 18 patients (mean and median ages 56-4 and 56-5 years, respectively) was cancer detected by mammography alone. Table ill shows the clinical, radiological, and pathological details of these patients. The cancers were diagnosed following localisation of the suspicious area on the mammogram with a flexible, self-retaining hooked-wire and subsequent excision. 3 of the 18 cancers were in the symptom-free breast; thus, in 15 symptomatic breasts the cancer was not diagnosed clinically. 7 of these 15 did not have a lump and therefore mammography was the initial investigation. These 7 had clinical signs noted which would, nevertheless, have been pursued to open biopsy. The signs were subtle skin tether, nipple inversion or discharge, peau
(77%) of the women who proved to have breast cancer presented with a palpable lump and the diagnosis could be made on clinical grounds, supported by needle biopsy. The sensitivity of mammography in this group was 88%, which is the upper limit of the range (61-87%) recorded in other studies.2-5 This high level of sensitivity can Most
the inclusion of 29 mammograms deemed indeterminate (even though the examiner knew the diagnosis of carcinoma) in the true positive group. All radiological techniques have their limitations, and about 10% of tumours are invisible even with the most up-to-date equipment and mammographic techniques. Of this 10%, about half the tumours are missed because of breast density and the other half do not show on mammograms, even in involuted breasts.6 The sensitivity of mammography is dependent on age: in young women interpretation of mammograms is often more difficult than in older women because of the greater density of the breast parenchyma. Edeiken,4in a study of 499 women with symptomatic breast disease showed a sensitivity for film mammography of 50% in patients less than 50 years of age, compared with 88% in women over 50 years. Conversely, Egeli and Urban3 found occult cancers in young patients with symptoms as often as in older women. We found only 18 cancers by mammography in 562 women with breast cancer, and 7 of these had clinical findings that would have led to an excisional biopsy. Thus, in only 11 cancers in 5080 patients would the diagnosis have been missed without mammography and 3 of these were in the symptom-free breast. We did mammograms in 5080 women ; around 20-30 occult cancers would be expected in this number of women in a screened, symptom-free population of 50 years of age or older. The present UK mammographic screening programme in 50-64-year-old women is detecting 4-6 invasive cancers per 1000 mammograms. Thus, the 11 unsuspected cancers we found be attributed
TABLE III-CLINICAL AND PATHOLOGICAL FEATURES IN
to
18 CANCERS DETECTED MAMMOGRAPHICALLY
(L) left, (R) right, D density, M/C microcalcification, PD parenchymal distortion, NAD nothing abnormal detected, SP spiculation, MF multifocal, DCISS carcinoma-in-situ, LCISS lobular carcinoma-in-situ, ILo invasive lobular carcinoma, IDu invasive ductal carcinoma, N node, + positive, -negative. *In non-symptomatic breast.
ductal
889
represent the gain, which is half to a third the number that would have been found by screening an equivalent number of symptom-free women aged 50 or over. There are several disadvantages of mammography in symptom-free women. Firstly, besides the 18 patients with clinically occult cancers, a further 74 underwent localisation biopsy for lesions subsequently shown to be benign on histology (a ratio of 1 malignant to 4 benign). Clearly, this represents a high proportion of unnecessary surgical
procedures. Secondly, a set of mammograms costs [,15, and the cost of
over 5000 is not inconsiderable. Thirdly, over-reliance on negative results from mammography alone is, without doubt, dangerous since there is a 10-20%
false-negative rate. Many general practitioners and other consultants refer
patients for mammography as the initial investigation for a breast symptom, and we have also seen patients under age 30 years referred for mammography. Occasionally, the investigation may precede or replace clinical examination, which can delay the diagnosis of malignant lesions, and thus adversely affect the outlook.7-9 Our policy is to use mammography in specific situations rather than to screen every woman who presents, irrespective of the symptom. Our results showed that under 3% of patients who underwent mammography for breast pain, pain and lumpiness, or lumpiness alone had breast cancer, and only 7 of these had a clinically occult carcinoma. Symptoms other than pain or lumpiness are clearly more worthy of investigation by mammography: recent onset of nipple inversion was caused by a malignancy in about 1 in 8 patients. In another study we have demonstrated the value of mammography in the investigation of single duct nipple discharged We believe further indications for mammography are a strong family history of breast cancer, the detection of multifocal or contralateral malignancy in proven breast cancer; and the surveillance of patients treated by excision and radiotherapy for primary disease. Had we adopted such a selective policy for the use of mammography 12 of the 18 occult cancers would have been detected and the overall number of mammograms would have been greatly reduced. We conclude that clinical findings are of paramount importance in patients with symptoms of breast disease. Such women should be referred to a clinician experienced in breast disease, and only after a thorough clinical examination of the breasts should the specialist decide whether mammography should be done. Correspondence should be addressed to A.
P. L.
REFERENCES 1. Breast Cancer Screening report to the Health Ministers of England, Wales, Scotland and Northern Ireland. London: DHSS, 1986. ISBN 0-11321071 X. 2. Feig SA, Schwartz GF, Nerlinger R, et al. Prognostic factors of breast neoplasms detected on screening by mammography and physical examination. Radiology 1979; 133: 577-82. 3. Egeli RA, Urban JA. Mammography in symptomatic women 50 years of age and under, and those over 50. Cancer 1979; 43: 878-82. 4. EdeikenS. Mammography and palpable cancer of the breast. Cancer 1988; 61: 263-65. 5. McClow MV, Williams AC. Mammographic examinations. Ann Surgery 1973; 177: 616-19. 6. Parsons CA. Mammographic features of malignancy. In: Parsons CA, ed. Diagnosis of breast disease imaging clinical features and pathology. Cambridge: Chapman and Hall, 1983. 142-91. 7 Mann BD, Giuliano AE, Bassett LH, et al. Delayed diagnosis of breast cancer as a result of normal mammograms. Arch Surgery 1983; 118: 23-29. 8. Walker QJ, Langlands AO. The misuse of mammography in the management of breast cancer. Med J Aust 1986, 145: 185-87 9. Langlands AO, Tiver KW. Significance of a negative mammogram in patients with a palpable breast tumour. Med J Aust 1982, i 30-31. 10. Locker AP, Galea MH, Ellis IO, et al. Microdochectomy for single duct discharge. Br J Surg 1988; 75: 700-01.
Communicable Disease HORIZONTAL TRANSMISSION OF HEPATITIS B VIRUS L. GRAY DAVIS1 DAVID J. WEBER2,3 STANLEY M. LEMON3
Department of Antimicrobial Therapy, Burroughs Wellcome Company, Research Triangle Park, North Carolina;1 Department of Epidemiology, School of Public Health,2 and Division of Infectious Diseases, Department of Medicine, School of Medicine,3 University of North Carolina at Chapel Hill, North Carolina, USA of seroprevalence surveys shows that horizontal transmission of hepatitis B virus (ie, that occurring without apparent parenteral, sexual, or perinatal exposure) is common in areas endemic for the virus. It occurs especially in pre-adolescent children. In developed countries, where endemicity of hepatitis B virus is low, horizontal transmission (probably via saliva or open wounds) may occur in households with a persistent carrier, but it is less efficient a means of infection than is sexual or perinatal transmission. Horizontal transmission also seems possible in pre-school day-care centres in developed countries, despite the small numbers of carriers in such places.
Summary
Meta-analysis
INTRODUCTION
HEPATITIS B virus (HBV), a major cause of chronic hepatitis and cirrhosis and, in many societies, an important factor in the development of hepatocellular carcinoma,1 is found worldwide, but its prevalence and predominant mode of transmission vary among geographic regions. Transmission of HBV is widely recognised to follow sexual2 parenteralor perinatal4 exposure. In contrast, horizontal transmission of the virus (which we define as virus transmission unrelated to recognised sexual, perinatal, or parenteral exposure) has received comparatively little attention, despite convincing evidence that it is important among children aged under 10 years, and perhaps the predominant mode of transmission in many populations. In the developed nations of North America and Western Europe, the prevalence of chronic HBV infection (determined by carriage rate of hepatitis B surface antigen [HBsAg]) is about 0-1-0-5%, and infection is acquired usually in adult life. In these societies, HBV infection is most often acquired through parenteral or sexual contact, and is common only in certain high-risk groups (eg, intravenous drug abusers and promiscuous homosexual men). In contrast, among the less developed nations of Southeast Asia, the Pacific basin, and sub-Saharan Africa, HBV infection is highly endemic. There most adults have serological evidence of previous HBV infection, and more than 1 in 10 adults may be a chronic carrier of the virus. Although in these societies HBV infection is often acquired at or near the time of birth from a carrier mother, more often infection occurs later in childhood, in the absence of identifiable maternal, sexual, or parenteral exposure to virus. This review will focus on such horizontal transmission of HBV, paying particular attention to its part in maintaining the endemicity of HBV in populations with a high prevalence of the virus, the mechanisms by which such transmission occurs, and the potential for its occurrence in the low endemicity populations of North America and Western Europe.
Hospital Practice
MAMMOGRAPHY IN
4518
562 PATIENTS WITH BREAST CANCER AND WITH BENIGN CONDITIONS
MAMMOGRAPHY IN SYMPTOMATIC BREAST DISEASE A. R. MANHIRE A. P. LOCKER VERDI STICKLAND JENNIFER CASELDINE R. W. BLAMEY
Department of Surgery, City Hospital, Nottingham NG5 1PB The contribution of mammography to the diagnosis of breast cancer was examined in 5080 patients with various breast symptoms. There were 562 breast cancers within this group. The sensitivity of mammography was 88%. Only 18 cancers were detected by mammography alone, and of these 3 were in the other breast. 7 of the remaining 15 cancers had clinical signs which would have been pursued to open biopsy in the absence of mammography. Clinical examination is of paramount importance in the management of patients with symptomatic breast disease. Mammography is most useful when applied in specific situations rather than to screen every patient with breast symptoms.
Summary
INTRODUCTION
EXAMINATION of the breast by mammography has become widely practised over the past 25 years, and a national mammographic breast screening programme1 has been introduced in the UK. Mammography is the method of choice for screening symptom-free women over 50 years of age but its value in the investigation of symptomatic breast disease is less well defined. If we wish to use mammography to investigate patients who present with symptoms we need to know whether a significant proportion of clinically occult breast cancers will be detected by this method. Furthermore the false-negative rate should not be high. Our aim was to evaluate the contribution of mammography in women presenting with various symptoms of breast disease, and to better defme the most effective use of mammographic facilities. MATERIALS AND METHODS
Since 1973 the breast unit at the City Hospital, Nottingham, has increasing numbers of women with various breast symptoms referred by general practitioners. There are now about 3000 new referrals a year. At the initial outpatient attendance, all patients were examined clinically by a senior member of the breast unit team. Biopsies were seen
10.
Morstyn G, Souza LM, Keech J, et al Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy Lancet 1988; i 667-72. 11. Gabrilove JL, Jakubowski A, Scher H, et al. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med 1988; 318: 1414-22. 12. Duhrsen U, Villeval J-L, Boyd J, et al. Effects of recombinant human granulocyte colony-stimulating factor on hemopoietic progenitor cells in cancer patients Blood 1988, 72: 2074-81. 13. Vadhan-Raj S, Buescher S, Broxmeyer HE, et al, Stimulation of myelopoiesis in patients with aplastic anemia by recombinant human granulocyte-macrophage colony-stimulating factor. N Engl JMed 1988; 319: 1628-34. 14 Groopman JE, Mitsuyasu RT, De Leo MJ, et al Effects of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 1987; 317: 593-98. 15 Brandt SJ, Peters WP, Atwater SK, et al. Effect of recombinant human granulocytemacrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N EnglJ Med 1988; 318: 869-76.
*Single duct. tMulti or single duct. done only on discrete breast lumps; where there were areas of thickening within the breast the patient was reassessed at the other phase of her menstrual cycle. Biopsies were generally done by ’Tru-cut’ needle but lately fme-needle aspiration cytology has been used. Referral for
mammography was at the discretion of the examining clinician; only patients under 30 years of age were specifically excluded. Biopsy was always done when a breast lump had been detected clinically but the mammogram was normal. Conversely, all patients with mammographic abnormalities were followed up or biopsies done if the examiner was worried. From our breast clinic records, we determined the main presenting symptom in all patients referred by their general practitioner between Jan 1, 1981 and Dec 31, 1987. Within this group the patients diagnosed as having breast cancer were identified, and we noted whether a breast lump was recorded as present on initial examination. We regarded a lump as present only if it had been recorded in diagrammatic or written form in the case notes or if the patient had undergone needle or excisional biopsy. The mammograms from all the patients with proven breast cancer were reviewed by one radiologist (A. R. M.) who was aware of the diagnosis in each case. Mammograms were classified as positive or negative for malignancy for each of the two projections (craniocaudal and 45’oblique), or as indeterminate if the films were difficult to interpret. RESULTS
In the
study period a total of 5080 patients with symptomatic breast disease had mammography at the City Hospital. 562 of these were diagnosed histologically as having invasive (545, 97%) or in-situ (17, 3%) breast cancers. The median age of the 562 patients was 54 years (range 30-78). 163 patients (29%) were aged 50 or less. The median age of the 4518 patients with benign conditions was J, Singer JW, Buckner CD, et al Use of recombinant human granulocyte-macrophage colony-stimulating factors in autologous marrow transplantanon for lymphoid malignancies. Blood 1988; 72: 834-36. 17. Vadhan-Raj S, Keating M, Le Maistre A, et al. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes N Engl J Med 1987; 317: 1545-52. 18. Antin JH, Smith BR, Holmes W, Rosenthal DS. Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome. Blood 1988; 72: 705-13. 19. Metcalf D. The molecular control of blood cells Boston Harvard University Press, 16. Nemunaitis
1988.
Begley CG, Metcalf D, Nicola NA Purified colony stimulating factors (G-CSF and GM-CSF) induce differentiation in HL60 leukemic cells with suppression of cloneogenicity. Int J Cancer 1987; 39: 99-105. 21. Metcalf D, Hilton DJ, Nicola NA. Clonal analysis of the actions of the murine leukemia inhibitory factor on leukemic and normal munne hemopoietic cells.
20.
Leukemia 1988, 2: 216-21. TM, Justement J, Kinter A, et al. Cytokine-induced expression of HIV-1in chronically infected promonocytic cell line. Science 1987; 238: 800-02.
22. Folks
a
888 TABLE II-RESULTS OF MAMMOGRAPHY IN
562
PATIENTS WITH
BREAST CANCER
d’orange, and a hard axillary gland. Thus, there were 8 patients in whom a carcinoma was present in the symptomatic breast with no clinical finding which would
biopsy. These patients had a median age of 565 years (range 37-68).
have led to
DISCUSSION
47 years
(range 30 to 74). Overall, in benign and malignant categories, 2908 (57%) women were under 50 years old. 12 patients had synchronous bilateral breast cancer, which we have defined as cancer detected in the other breast diagnosis or within three months. In 9 of these patients, both carcinomas were palpable. In the remaining 3 the cancer in the other breast was detected by mammography. Table I shows the principal presenting symptom in the 562 patients with breast cancer and the 4518 with benign conditions. 72% of the cancers were diagnosed by tru-cut needle biopsy; 6% had fine-needle aspiration cytology only, and in 21 % an excisional biopsy was needed, usually because the tru-cut biopsy specimen was inadequate or benign. Occasionally the lump was too small for needle biopsy. In 9 (1-6%) patients Paget’s disease was diagnosed at
by nipple biopsy. Table n shows the results of the radiologist’s review of the mammograms. If we include the indeterminate category as positive for breast cancer the sensitivity of mammography in the detection of known cancers is 87-9%. Thus 68 (12%) patients had no mammographic evidence of breast cancer, the diagnosis being made solely by clinical examination and
biopsy. In only 18 patients (mean and median ages 56-4 and 56-5 years, respectively) was cancer detected by mammography alone. Table ill shows the clinical, radiological, and pathological details of these patients. The cancers were diagnosed following localisation of the suspicious area on the mammogram with a flexible, self-retaining hooked-wire and subsequent excision. 3 of the 18 cancers were in the symptom-free breast; thus, in 15 symptomatic breasts the cancer was not diagnosed clinically. 7 of these 15 did not have a lump and therefore mammography was the initial investigation. These 7 had clinical signs noted which would, nevertheless, have been pursued to open biopsy. The signs were subtle skin tether, nipple inversion or discharge, peau
(77%) of the women who proved to have breast cancer presented with a palpable lump and the diagnosis could be made on clinical grounds, supported by needle biopsy. The sensitivity of mammography in this group was 88%, which is the upper limit of the range (61-87%) recorded in other studies.2-5 This high level of sensitivity can Most
the inclusion of 29 mammograms deemed indeterminate (even though the examiner knew the diagnosis of carcinoma) in the true positive group. All radiological techniques have their limitations, and about 10% of tumours are invisible even with the most up-to-date equipment and mammographic techniques. Of this 10%, about half the tumours are missed because of breast density and the other half do not show on mammograms, even in involuted breasts.6 The sensitivity of mammography is dependent on age: in young women interpretation of mammograms is often more difficult than in older women because of the greater density of the breast parenchyma. Edeiken,4in a study of 499 women with symptomatic breast disease showed a sensitivity for film mammography of 50% in patients less than 50 years of age, compared with 88% in women over 50 years. Conversely, Egeli and Urban3 found occult cancers in young patients with symptoms as often as in older women. We found only 18 cancers by mammography in 562 women with breast cancer, and 7 of these had clinical findings that would have led to an excisional biopsy. Thus, in only 11 cancers in 5080 patients would the diagnosis have been missed without mammography and 3 of these were in the symptom-free breast. We did mammograms in 5080 women ; around 20-30 occult cancers would be expected in this number of women in a screened, symptom-free population of 50 years of age or older. The present UK mammographic screening programme in 50-64-year-old women is detecting 4-6 invasive cancers per 1000 mammograms. Thus, the 11 unsuspected cancers we found be attributed
TABLE III-CLINICAL AND PATHOLOGICAL FEATURES IN
to
18 CANCERS DETECTED MAMMOGRAPHICALLY
(L) left, (R) right, D density, M/C microcalcification, PD parenchymal distortion, NAD nothing abnormal detected, SP spiculation, MF multifocal, DCISS carcinoma-in-situ, LCISS lobular carcinoma-in-situ, ILo invasive lobular carcinoma, IDu invasive ductal carcinoma, N node, + positive, -negative. *In non-symptomatic breast.
ductal
889
represent the gain, which is half to a third the number that would have been found by screening an equivalent number of symptom-free women aged 50 or over. There are several disadvantages of mammography in symptom-free women. Firstly, besides the 18 patients with clinically occult cancers, a further 74 underwent localisation biopsy for lesions subsequently shown to be benign on histology (a ratio of 1 malignant to 4 benign). Clearly, this represents a high proportion of unnecessary surgical
procedures. Secondly, a set of mammograms costs [,15, and the cost of
over 5000 is not inconsiderable. Thirdly, over-reliance on negative results from mammography alone is, without doubt, dangerous since there is a 10-20%
false-negative rate. Many general practitioners and other consultants refer
patients for mammography as the initial investigation for a breast symptom, and we have also seen patients under age 30 years referred for mammography. Occasionally, the investigation may precede or replace clinical examination, which can delay the diagnosis of malignant lesions, and thus adversely affect the outlook.7-9 Our policy is to use mammography in specific situations rather than to screen every woman who presents, irrespective of the symptom. Our results showed that under 3% of patients who underwent mammography for breast pain, pain and lumpiness, or lumpiness alone had breast cancer, and only 7 of these had a clinically occult carcinoma. Symptoms other than pain or lumpiness are clearly more worthy of investigation by mammography: recent onset of nipple inversion was caused by a malignancy in about 1 in 8 patients. In another study we have demonstrated the value of mammography in the investigation of single duct nipple discharged We believe further indications for mammography are a strong family history of breast cancer, the detection of multifocal or contralateral malignancy in proven breast cancer; and the surveillance of patients treated by excision and radiotherapy for primary disease. Had we adopted such a selective policy for the use of mammography 12 of the 18 occult cancers would have been detected and the overall number of mammograms would have been greatly reduced. We conclude that clinical findings are of paramount importance in patients with symptoms of breast disease. Such women should be referred to a clinician experienced in breast disease, and only after a thorough clinical examination of the breasts should the specialist decide whether mammography should be done. Correspondence should be addressed to A.
P. L.
REFERENCES 1. Breast Cancer Screening report to the Health Ministers of England, Wales, Scotland and Northern Ireland. London: DHSS, 1986. ISBN 0-11321071 X. 2. Feig SA, Schwartz GF, Nerlinger R, et al. Prognostic factors of breast neoplasms detected on screening by mammography and physical examination. Radiology 1979; 133: 577-82. 3. Egeli RA, Urban JA. Mammography in symptomatic women 50 years of age and under, and those over 50. Cancer 1979; 43: 878-82. 4. EdeikenS. Mammography and palpable cancer of the breast. Cancer 1988; 61: 263-65. 5. McClow MV, Williams AC. Mammographic examinations. Ann Surgery 1973; 177: 616-19. 6. Parsons CA. Mammographic features of malignancy. In: Parsons CA, ed. Diagnosis of breast disease imaging clinical features and pathology. Cambridge: Chapman and Hall, 1983. 142-91. 7 Mann BD, Giuliano AE, Bassett LH, et al. Delayed diagnosis of breast cancer as a result of normal mammograms. Arch Surgery 1983; 118: 23-29. 8. Walker QJ, Langlands AO. The misuse of mammography in the management of breast cancer. Med J Aust 1986, 145: 185-87 9. Langlands AO, Tiver KW. Significance of a negative mammogram in patients with a palpable breast tumour. Med J Aust 1982, i 30-31. 10. Locker AP, Galea MH, Ellis IO, et al. Microdochectomy for single duct discharge. Br J Surg 1988; 75: 700-01.
Communicable Disease HORIZONTAL TRANSMISSION OF HEPATITIS B VIRUS L. GRAY DAVIS1 DAVID J. WEBER2,3 STANLEY M. LEMON3
Department of Antimicrobial Therapy, Burroughs Wellcome Company, Research Triangle Park, North Carolina;1 Department of Epidemiology, School of Public Health,2 and Division of Infectious Diseases, Department of Medicine, School of Medicine,3 University of North Carolina at Chapel Hill, North Carolina, USA of seroprevalence surveys shows that horizontal transmission of hepatitis B virus (ie, that occurring without apparent parenteral, sexual, or perinatal exposure) is common in areas endemic for the virus. It occurs especially in pre-adolescent children. In developed countries, where endemicity of hepatitis B virus is low, horizontal transmission (probably via saliva or open wounds) may occur in households with a persistent carrier, but it is less efficient a means of infection than is sexual or perinatal transmission. Horizontal transmission also seems possible in pre-school day-care centres in developed countries, despite the small numbers of carriers in such places.
Summary
Meta-analysis
INTRODUCTION
HEPATITIS B virus (HBV), a major cause of chronic hepatitis and cirrhosis and, in many societies, an important factor in the development of hepatocellular carcinoma,1 is found worldwide, but its prevalence and predominant mode of transmission vary among geographic regions. Transmission of HBV is widely recognised to follow sexual2 parenteralor perinatal4 exposure. In contrast, horizontal transmission of the virus (which we define as virus transmission unrelated to recognised sexual, perinatal, or parenteral exposure) has received comparatively little attention, despite convincing evidence that it is important among children aged under 10 years, and perhaps the predominant mode of transmission in many populations. In the developed nations of North America and Western Europe, the prevalence of chronic HBV infection (determined by carriage rate of hepatitis B surface antigen [HBsAg]) is about 0-1-0-5%, and infection is acquired usually in adult life. In these societies, HBV infection is most often acquired through parenteral or sexual contact, and is common only in certain high-risk groups (eg, intravenous drug abusers and promiscuous homosexual men). In contrast, among the less developed nations of Southeast Asia, the Pacific basin, and sub-Saharan Africa, HBV infection is highly endemic. There most adults have serological evidence of previous HBV infection, and more than 1 in 10 adults may be a chronic carrier of the virus. Although in these societies HBV infection is often acquired at or near the time of birth from a carrier mother, more often infection occurs later in childhood, in the absence of identifiable maternal, sexual, or parenteral exposure to virus. This review will focus on such horizontal transmission of HBV, paying particular attention to its part in maintaining the endemicity of HBV in populations with a high prevalence of the virus, the mechanisms by which such transmission occurs, and the potential for its occurrence in the low endemicity populations of North America and Western Europe.