BRITISH MEDICAL JOURNAL
175
15 JULY 1978
MEDICAL PRACTICE
Contemporary Themes
Screening for breast cancer Report from Edinburgh Breast Screening Clinic* British Medical journal, 1978, 2, 175-178
Summary and conclusions As part of a trial to determine the feasibility of screening for breast cancer, 3952 women aged 40-59 years were screened once or more over two years. They represented 82% of those invited by a personal letter from their GPs. Each woman underwent mammography, two clinical examinations, and, usually, thermography. Further investigations included needle aspiration of cysts, xeromammography, and biopsy. Of the 125 women who underwent biopsy, 18 proved to have cancer. Because of the high response rate and consequent large sample of normal women the biopsy and cancer detection rates were low. Clinical examination and mammography together were more effective in detecting significant lesions than either procedure alone, and knowledge of the mammographic findings enabled the examiner to detect more abnormalities. Screening was expensive: each cancer detected cost about £6000, excluding data processing, surgical, and pathological costs. The clinic has now adopted a more simplified screening regimen, which should reduce costs, but more accurate imaging techniques and ways of identifying high-risk cases are needed.
Introduction Edinburgh is one of four centres designated to test the feasibility of screening for breast cancer. A purpose-built clinic, separate from any hospital, started screening of invited women on 1 September 1975. By 30 June 1977 3952 women had been examined, 2242 of them twice after a one-year interval. We describe here the methods and results of screening.
Methods Every woman aged 40-59 on the age-sex registers of 11 practices was sent an invitation, signed by her general practitioner, to attend the screening clinic. Only women already being treated for breast disease or those too ill to attend were excluded. If there was no response a second letter was sent four to six weeks later. The staff were all women, mostly married and about the same age as the attenders. The clinical director, senior secretary-receptionist, state-enrolled nurse, and darkroom technician were full-time; five medical officers, five radiographers, and three clerical assistants worked part-time. The clinic was designed to enable examinations to be completed as rapidly as possible in pleasant and private surroundings. On arrival each woman was allocated to an examination room, which she left only for thermography and mammography.
METHODS OF SCREENING
As one of the objectives was to evaluate observer variation each woman underwent two clinical examinations, and the findings on mammography and thermography were interpreted blind by two of
the medical staff. The executive committee of the clinic are: Professor E Samuel, department of medical radiology, Professor A P M Forrest, department of clinical surgery, Dr T J Anderson, department of pathology, Dr P Mary Fulton, department of community medicine, and Mr W Lutz, medical computing and statistics unit, University of Edinburgh; Dr C Brough and Dr Nancy B Loudon, Lothian Health Board; Dr W Forbes, Scottish Home and Health Department; and Dr Anne M Scott, Breast Screening Clinic, Edinburgh. *
Thermography was performed first, using the Barr and Stroud thermography unit. The problems that we have experienced with this will be discussed elsewhere. Mammography-This was also done before clinical examination, using the GEC Mammostand and Medichrome film in a vacuum pack with a single fine tungsten back screen.1 2 Craniocaudal and mediolateral views of each breast were taken. KVp was between 25 and 27 with fixed mA of 250 and exposure times of 0 04 to 0 08 second,
176
BRITISH MEDICAL JOURNAL
giving total mAs usually between 40 and 70 for all four films. Radiation doses on the skin of the upper inner quadrant of the right breast averaged 0 4 rad for the complete examination of both breasts. Films were
processed and checked for quality before each
woman
left the
clinic. The first medical examiner took a clinical history, which included details of breast symptoms, menstrual history, age at menarche and at first delivery, pregnancies, lactation, oral contraceptives and other hormones, family history of breast cancer, and any other relevant diseases. The same doctor then examined the breasts and axillae, with the subject sitting and recumbent. A second medical officer examined the woman independently, without access to the history. Each woman spent 45 to 50 minutes in the clinic, including 10 to 15 minutes cooling time before thermography. Twelve to 14 women (with a maximum of 18) were normally screened in a three and a halfhour session.
15 JULY 1978
DATA PROCESSING
Data processing was performed by the Edinburgh University medical computing and statistics unit, using a key to disc system with storage of records on magnetic tape. Regular quarterly listings and tabulations were sent to the clinic. Special information was supplied on demand.
Results
RECORDINGS OF FINDINGS
The information obtained by each examiner was recorded on individual forms and the coded results summarised on a separate form, which showed at a glance any abnormality and any difference between the two examiners. Studies on observer variation will be reported elsewhere. Records that showed all results as normal were completed by the clinic secretary and routine reports of no significant abnormality were sent immediately to both the woman and her general practitioner, along with notification of yearly recall. Records with any abnormal result were passed to the clinical director, who assessed the combined findings. When an abnormality was found or suspected an individual letter was sent to the general practitioner to inform him of any further action. The woman herself was advised, either in the clinic or by letter, of the need for further investigations or review.
Altogether 5321 letters were sent, of which 420 were returned as "not known." Of the 4901 women who were therefore assumed to have received the invitation 4007 (81-8%,o) attended. (Fifty-five were later found to be outside the age group and, although screened, were excluded from the statistics.) Two hundred and eighty-one women refused to attend and the other 613 failed to respond. The response rate to invitation for second annual screening is currently 84% of those who attended the first time. The age, social class, and marital status of those screened are shown in table I. On questioning, 309 women admitted to having breast symptoms, for which no specific action had been taken and 722 had a past history of breast complaints (table II). Five hundred and fortytwo women gave a family history of breast cancer in 644 relatives.
TABLE iI-Details of symptoms at time of screening and past symiptoms and investigations
Symptoms FURTHER INVESTIGATIONS
Cytology-Needle aspiration was performed on palpable masses. Cysts were aspirated to dryness and fluid sent for cytology, while smears of tissue were taken from solid masses. The woman was asked to attend the review clinic three weeks after cyst aspiration or one week after aspiration of a solid mass. Review clinic-This was held once a week by ES, APMF, and AMS. Women with positive clinical or mammographic findings were reexamined. If the interpretation of their Medichrome films was in doubt xeromammography was arranged either before or at the review clinic. Biopsies were also arranged at the clinic. If biopsy was not recommended the woman was given another appointment within a year. Biopsy was indicated when there was refilling or a residual mass after cyst aspiration and when a discrete, palpable, non-cystic mass or an area of abnormal thickening was present. It was also performed when mammographic lesions suggested cancer, irrespective of the clinical findings. These lesions were: (a) fine calcification, clustered or profuse, (b) disturbance of normal architecture, or (c) an unexplained opacity or localised increase in density. A 48-hour biopsy service was established in the short-stay surgical unit at Longmore Hospital and women were usually admitted one to two weeks after attending the review clinic. In cases of non-palpable mammographic lesions x-ray localisation of the suspect area was required immediately before surgery. Biopsy techniques have been described elsewhere.3 Immediate examination by frozen section was rarely used. Instead the specimens were examined radiologically, and paraffin sections were made of selected areas. When the lesion proved benign the woman was referred back to the screening clinic for routine annual rescreening. When it proved malignant she was treated by mastectomy, provided staging investigations showed no evidence of metastases.
No with symptoms
Past symptoms and investigations
attendance
No with symptoms
No who underwent biopsy
No who underwent cyst aspiration
25 32
272 39
198 5
7
203
7
at
Lump(s) Nipple discharge Local pain Discomfort (other than premenstrual) Lumpiness Other Abscess Total
32 126 6 88
250
309
722
161
ABNORMALITIES FOUND
At the first screening 2824 (71-500) women had no abnormality and 915 (23 21") had "diffuse benign disease" requiring no action, and 213 (5-40o) needed further investigation. Ninety-three women (80 of whom attended the review clinic) underwent xeromammography, and 25 had cyst aspirations. A total of 179 women attended the review clinic: 75 did not need immediate treatment, but 21 of these were
recalled at three or six months. Altogether 90 (2 3°') women underwent biopsy (nine bilateral) as a result of initial screening. They included three who had cysts aspirated, 33 who had non-palpable mammographic lesions, and eight who had reattended the review clinic after three to six months. Eleven women were found to have cancer of the breast. After second annual screening 35 women were referred for biopsy (three bilateral) and seven had cancer. One hundred and twenty-five women (137 breasts) therefore had a lesion worthy of biopsy, and 18 were found to have cancer. The primary methods of detection are shown in table III.
TABLE i-Details of patients screened Social class I II III IV V Other
No
(0.)
386 (10) 1069 (27) 1946 (49) 372 (9) 122 (3) 57 (1)
Age 40-44 45-49 50-54 55-59
No (%) 891 1034 1082 945
Marital state
No
No who were nulliparous
(23) (26) (27)
Married Single Divorced or separated
(24)
Widowed
3036 503 152 261
360 462 11 29
BRITISH MEDICAL JOURNAL
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15 JULY 1978
TABLE iII-Primary methods of detecting a lesion requiring biopsy Findings on biopsy Benign
Malignant
Total
37
1
54 25
9 8
38 63 33
116
18
134
18
137
Clinical Clinical and mammography Mammography Total
3
3
Neither*
Grand total
119
*"Mirror" biopsies of second breast in three patients with cancer.
ACCURACY OF DIAGNOSIS
The preoperative diagnosis was based on a consensus of the findings at initial examination and review clinic and the results of other investigations. The accuracy of this in the 137 biopsied breasts in 125 women is shown in table IV. Of 31 lesions suspected of being malignant 19 proved to be benign and of 106 thought to be benign six proved to be malignant. Two of the seven cancers diagnosed at second screening had, on review of their findings, shown some suspicious signs at first screening.
Preoperative diagnosis Benign
Probably benign
Probably malignant
Normal Mammary dysplasia Dysplasia with atypia Fibroadenoma Other benign Carcinoma: Invasive Non-invasive Total
TABLE v-Comparison of populations and findings of screening programmes
Centre
Malignant
Total 9 60 25 18 7
4 29 11 13 5
4 20 9 4 1
1 9 5 1 1
2 1
3
4 2
6
1 18
65
41
23
8
137
2
Thirty-three women underwent biopsy for non-palpable mammographic lesions. Of 15 with suspicious-looking calcification only one proved to have cancer; of eight with "disturbed architecture," three had cancer; and of 10 with suspicious-looking opacities (two spiculated), four had cancer.
TYPES OF CARCINOMA
Fifteen of the 18 cancers were invasive and six also affected the Of the three non-invasive cancers, two were impalpable and intraduct histologically; the third had a palpable nodule and was a lobular carcinoma in situ. Of the other six impalpable cancers four were early tumours (two measuring under 1 cm) but the other two also affected the axillary nodes, although the actual tumours measured under 1 5 cm.
axillary nodes.
Discussion and conclusions Our response rate of 81 8" 0 to the invitation for screening was much higher than the 6500 in the Health Insurance Plan (HIP) study, New York,4 and the 540o/ in the south Manchester study.5 This was probably due to the fact that the general practitioners signed each letter; many women said that they came only because their doctor asked them to. This high response, ensuring a good sample of normal women, influenced the biopsy rate and cancer detection rate. Our rates were much lower than in the west London6 and south Manchester5 studies, in which self-referred women were admitted and the upper age limit was higher (table V). The equally high
Women screened
Edinburgh
Invited
Ealing6 BUPA9
Invited Invited Self-referred Self-referred Self-referred
(present series) HIP4 Manchester'
TABLE IV-Correlation of preoperative and final diagnoses
Histology
response for annual rescreening (also over 80%) indicates the acceptability of the procedure. Many women appreciated both the opportunity to be screened and the way in which it was conducted. Mammography proved more sensitive than clinical examination in detecting the small number of cancers. The findings of the HIP study suggested that mammography was of no benefit in women under 50.' Our numbers were too small to confirm or refute this suggestion, but six of the 18 cancers found occurred in women under 50 and all were seen on mammography, one being impalpable. As in other studies, a combination of clinical examination and mammography proved more effective than either alone. It is important to repeat clinical examination of the breast with knowledge of positive mammographic findings. When the examiner is alerted to an area of suspicion a clinical abnormality
Age (years)
No of patients
rate per 1000
Cancer rate per 1000 on initial screening
Biopsy
40-60
3952
23-3
2-8
40-64 -50 All ages > 35 All ages
20211 1611 1055 1000 11654
25-2 29 59 7 91 Not stated
2 72 10 6-6 12 6-86*
*Not stated whether initial screening examination only. Reproduced from British Jourtnal of Surgery, 1977, 64, 727, with Edinburgh figures updated.
that was previously overlooked is often discovered. Ten out of 33 cases reported normal at the initial clinical examination were found to have a palpable lesion once the presence of a mammographic abnormality was known. We therefore think that the most effective way of screening well women in this age group is to perform low-dose mammography first followed by history taking and examination by one examiner with simultaneous reporting of mammograms by a second examiner. Then both examiners should discuss the mammograms and clinical findings, and, if necessary, the woman can be re-examined immediately. A firm opinion can therefore be given at a woman's first attendance and a normal result intimated immediately. The number of impalpable lesions detected by mammography indicates the importance of developing techniques for accurate preoperative localisation and for confirming that the lesion has been removed.' Our aim is to remove the lesion with least disturbance. In these minimal lesions preoperative diagnosis by frozen section has little part to play, and histological techniques should be carefully standardised. Should the lesion prove to be cancer on excision biopsy, accurate staging of the patient is an essential part of management and should precede definitive treatment. 8 In the HIP study 10 5%; of cancers detected by screening were non-invasive and 70 50/% did not affect the axillary nodes.7 In our small series three of the 18 cancers were non-invasive and 12 did not affect the nodes. Because we double-checked all examinations and sent out specific appointments and reports to each woman by mail, screening proved expensive. Each screening examination cost about C16-50 and each cancer detected about £6000 exclusive of data processing, surgical and pathological costs. Considerable savings could be achieved by discontinuing thermography and routine double-checking; modifying the appointments system; and introducing the regimen for screening suggested above. In the light of this experience, more invited women are currently being examined by the simplified regimen. Those with no abnormality have been grateful for an immediate report and the clerical burden has been considerably reduced. To date two
178
women have been found to have cancer out of about 600 examined. We are convinced that screening well women contributes to the overall management of breast cancer. At the present rate of detection it is expensive, and efforts must be directed towards making major improvements in imaging techniques and identifying women with a high risk of developing breast cancer. We thank the following people, without whom the study could not have been carried out: Dr S M Shaw and the other clinical medical officers and radiographers; the clerical and other staff, especially Mrs J Anderson and Mrs A Renton; Dr G B Young for help with reporting mammograms; Mr A M C Owen, Mr M C Wilson, and other surgeons who did many of the biopsies; the general practitioners; the staff of the medical computing and statistics unit; the Lothian Health Board and the Scottish Home and Health Department; and Mr G H Mooney of the Health Economics Research Unit for his costing studies.
BRITISH MEDICAL JOURNAL
15 JULY 1978
We also thank the editor of the British J7ournal of Surgery for permission to reproduce table V. Requests for reprints should be sent to Dr Anne Scott, Breast Screening Clinic, Springwell House, Ardmillan Terrace, Edinburgh EH11 2JL.
References 1
Young, G B, British Journal of Radiology, 1974, 47, 811. 2Price, J L, and Butler, P D, X-ray Bulletin, 1971, 19, 3. 3 Owen, A M C, et al, British Journal of Surgery, 1977, 64, 725. Shapiro, S, et al, Proceedings of the National Cancer Conference, 1973, 7, 663. George, W D, et al, British Medical3Journal, 1976, 2, 858. 6 Chamberlain, J, et al, Lancet, 1975, 2, 1026. 7Shapiro, S, Cancer, 1977, 39, 2772. 8 Cant, E L, et al, World Journal of Surgery, 1977, 1, 303. 9 Bailey, A, et al, Clinical Oncology, 1976, 2, 317.
(Accepted 23 February 1978)
Screening for breast cancer Statement by British Breast Group* British Medical3Journal, 1978, 2, 178-180
In 1975 we published our first statement about screening for breast cancer.' Earlier this year we organised a symposium on this subject to review progress in the field, both in Britain and abroad, as a result of which we have updated some of our views. Following the controlled study of benefits of screening for breast cancer by physical examination and mammography, carried out by the Health Insurance Plan (HIP) in New York,2 the American Cancer Society and the National Cancer Institute set up 29 breast cancer detection demonstration programmes in different parts of the United States. These screened some 280 000 women aged 35-74. Subsequently, questions were raised about the safety of x-ray mammography and also about the malignancy of a proportion of the lesions of less than 1 cm in diameter that were detected in the demonstration programmes. A National Institutes of Health-National Cancer Institute panel was therefore set up to review the breast cancer screening controversy. The chairman, Dr S 0 Thier, has recently discussed six key questions arising from the work of that panel, which we think apply as much to this country as to the United States,3 and on which we want to comment.
What is meant by "screening" for breast cancer? Screening means the investigation of women who believe themselves to be free from symptoms and signs of breast disease. Anxiety about the possible hazards of mammography affects particularly these women rather than those who present with a problem that needs evaluation. *Members of the group are: Mr Michael Baum, Mr E A Benson, Mr Roger Blamey, Dr Diana Brinkley, Mr Ian Burn, Dr R D Bulbrook (chairman), Professor Alfred Cuschieri, Dr J A Dossett, Professor A P M Forrest, Mr David George, Dr Huw Gravelle, Professor Keith Griffiths, Dr John Haybittle, Mr John Hayward, Dr Roger King, Dr Peter Maguire, Dr Rosemary Millis, Professor J G Murray, Professor Munro Neville, Dr Trevor Powles, Dr Maureen Roberts (secretary), Dr R D Reubens, Professor R A Sellwood, Professor Roger Short, Dr Helen Stewart, Dr Basil Stoll, and Professor Martin Vessey.
Some centres in Britain, in presenting the results of their screening programmes, combined data about (a) women invited to participate, (b) those who referred themselves (who often suspected an abnormality), and (c) those specifically referred by a doctor for special investigation. This practice was responsible for much of the difficulty experienced in comparing different studies and in assessing the load which the screening of truly asymptomatic women would place on diagnostic and surgical services. What is the evidence that women benefit from screening? Unless a benefit is very large a randomised controlled trial is the only method of evaluation whereby interminable debate can be avoided. For breast cancer screening the HIP study remains the only investigation of this type, although a further randomised controlled trial, in which "single view" mammography is to be evaluated as the sole method of screening, is in progress in Sweden.4 It should be noted that the reduction in breast cancer mortality in the HIP study, which included 30 000 women who were screened and 30 000 controls, was limited to women aged over 50 years. Although experience elsewhere suggests that the results of a single controlled trial may be misleading, we are none the less convinced that early diagnosis of breast cancer is important and that it improves the survival rate. We would like to emphasise that screening programmes in which women refer themselves cannot provide significant further evidence of benefit. Studies in which a serious attempt is made to screen all women of a given age group in a particular geographical area and in which breast cancer mortality is subsequently monitored (both among the screened and among the unscreened) can yield such evidence, especially if data are also collected in control areas. Such a study is in progress in Holland,5 while proposals are in hand to start a similar investigation in Britain. What are the risks of mammography? Information about the carcinogenic effects of ionising radiation on the breast has been obtained from Japanese atomic bomb survivors, from women undergoing fluoroscopy of the chest to
175
15 JULY 1978
MEDICAL PRACTICE
Contemporary Themes
Screening for breast cancer Report from Edinburgh Breast Screening Clinic* British Medical journal, 1978, 2, 175-178
Summary and conclusions As part of a trial to determine the feasibility of screening for breast cancer, 3952 women aged 40-59 years were screened once or more over two years. They represented 82% of those invited by a personal letter from their GPs. Each woman underwent mammography, two clinical examinations, and, usually, thermography. Further investigations included needle aspiration of cysts, xeromammography, and biopsy. Of the 125 women who underwent biopsy, 18 proved to have cancer. Because of the high response rate and consequent large sample of normal women the biopsy and cancer detection rates were low. Clinical examination and mammography together were more effective in detecting significant lesions than either procedure alone, and knowledge of the mammographic findings enabled the examiner to detect more abnormalities. Screening was expensive: each cancer detected cost about £6000, excluding data processing, surgical, and pathological costs. The clinic has now adopted a more simplified screening regimen, which should reduce costs, but more accurate imaging techniques and ways of identifying high-risk cases are needed.
Introduction Edinburgh is one of four centres designated to test the feasibility of screening for breast cancer. A purpose-built clinic, separate from any hospital, started screening of invited women on 1 September 1975. By 30 June 1977 3952 women had been examined, 2242 of them twice after a one-year interval. We describe here the methods and results of screening.
Methods Every woman aged 40-59 on the age-sex registers of 11 practices was sent an invitation, signed by her general practitioner, to attend the screening clinic. Only women already being treated for breast disease or those too ill to attend were excluded. If there was no response a second letter was sent four to six weeks later. The staff were all women, mostly married and about the same age as the attenders. The clinical director, senior secretary-receptionist, state-enrolled nurse, and darkroom technician were full-time; five medical officers, five radiographers, and three clerical assistants worked part-time. The clinic was designed to enable examinations to be completed as rapidly as possible in pleasant and private surroundings. On arrival each woman was allocated to an examination room, which she left only for thermography and mammography.
METHODS OF SCREENING
As one of the objectives was to evaluate observer variation each woman underwent two clinical examinations, and the findings on mammography and thermography were interpreted blind by two of
the medical staff. The executive committee of the clinic are: Professor E Samuel, department of medical radiology, Professor A P M Forrest, department of clinical surgery, Dr T J Anderson, department of pathology, Dr P Mary Fulton, department of community medicine, and Mr W Lutz, medical computing and statistics unit, University of Edinburgh; Dr C Brough and Dr Nancy B Loudon, Lothian Health Board; Dr W Forbes, Scottish Home and Health Department; and Dr Anne M Scott, Breast Screening Clinic, Edinburgh. *
Thermography was performed first, using the Barr and Stroud thermography unit. The problems that we have experienced with this will be discussed elsewhere. Mammography-This was also done before clinical examination, using the GEC Mammostand and Medichrome film in a vacuum pack with a single fine tungsten back screen.1 2 Craniocaudal and mediolateral views of each breast were taken. KVp was between 25 and 27 with fixed mA of 250 and exposure times of 0 04 to 0 08 second,
176
BRITISH MEDICAL JOURNAL
giving total mAs usually between 40 and 70 for all four films. Radiation doses on the skin of the upper inner quadrant of the right breast averaged 0 4 rad for the complete examination of both breasts. Films were
processed and checked for quality before each
woman
left the
clinic. The first medical examiner took a clinical history, which included details of breast symptoms, menstrual history, age at menarche and at first delivery, pregnancies, lactation, oral contraceptives and other hormones, family history of breast cancer, and any other relevant diseases. The same doctor then examined the breasts and axillae, with the subject sitting and recumbent. A second medical officer examined the woman independently, without access to the history. Each woman spent 45 to 50 minutes in the clinic, including 10 to 15 minutes cooling time before thermography. Twelve to 14 women (with a maximum of 18) were normally screened in a three and a halfhour session.
15 JULY 1978
DATA PROCESSING
Data processing was performed by the Edinburgh University medical computing and statistics unit, using a key to disc system with storage of records on magnetic tape. Regular quarterly listings and tabulations were sent to the clinic. Special information was supplied on demand.
Results
RECORDINGS OF FINDINGS
The information obtained by each examiner was recorded on individual forms and the coded results summarised on a separate form, which showed at a glance any abnormality and any difference between the two examiners. Studies on observer variation will be reported elsewhere. Records that showed all results as normal were completed by the clinic secretary and routine reports of no significant abnormality were sent immediately to both the woman and her general practitioner, along with notification of yearly recall. Records with any abnormal result were passed to the clinical director, who assessed the combined findings. When an abnormality was found or suspected an individual letter was sent to the general practitioner to inform him of any further action. The woman herself was advised, either in the clinic or by letter, of the need for further investigations or review.
Altogether 5321 letters were sent, of which 420 were returned as "not known." Of the 4901 women who were therefore assumed to have received the invitation 4007 (81-8%,o) attended. (Fifty-five were later found to be outside the age group and, although screened, were excluded from the statistics.) Two hundred and eighty-one women refused to attend and the other 613 failed to respond. The response rate to invitation for second annual screening is currently 84% of those who attended the first time. The age, social class, and marital status of those screened are shown in table I. On questioning, 309 women admitted to having breast symptoms, for which no specific action had been taken and 722 had a past history of breast complaints (table II). Five hundred and fortytwo women gave a family history of breast cancer in 644 relatives.
TABLE iI-Details of symptoms at time of screening and past symiptoms and investigations
Symptoms FURTHER INVESTIGATIONS
Cytology-Needle aspiration was performed on palpable masses. Cysts were aspirated to dryness and fluid sent for cytology, while smears of tissue were taken from solid masses. The woman was asked to attend the review clinic three weeks after cyst aspiration or one week after aspiration of a solid mass. Review clinic-This was held once a week by ES, APMF, and AMS. Women with positive clinical or mammographic findings were reexamined. If the interpretation of their Medichrome films was in doubt xeromammography was arranged either before or at the review clinic. Biopsies were also arranged at the clinic. If biopsy was not recommended the woman was given another appointment within a year. Biopsy was indicated when there was refilling or a residual mass after cyst aspiration and when a discrete, palpable, non-cystic mass or an area of abnormal thickening was present. It was also performed when mammographic lesions suggested cancer, irrespective of the clinical findings. These lesions were: (a) fine calcification, clustered or profuse, (b) disturbance of normal architecture, or (c) an unexplained opacity or localised increase in density. A 48-hour biopsy service was established in the short-stay surgical unit at Longmore Hospital and women were usually admitted one to two weeks after attending the review clinic. In cases of non-palpable mammographic lesions x-ray localisation of the suspect area was required immediately before surgery. Biopsy techniques have been described elsewhere.3 Immediate examination by frozen section was rarely used. Instead the specimens were examined radiologically, and paraffin sections were made of selected areas. When the lesion proved benign the woman was referred back to the screening clinic for routine annual rescreening. When it proved malignant she was treated by mastectomy, provided staging investigations showed no evidence of metastases.
No with symptoms
Past symptoms and investigations
attendance
No with symptoms
No who underwent biopsy
No who underwent cyst aspiration
25 32
272 39
198 5
7
203
7
at
Lump(s) Nipple discharge Local pain Discomfort (other than premenstrual) Lumpiness Other Abscess Total
32 126 6 88
250
309
722
161
ABNORMALITIES FOUND
At the first screening 2824 (71-500) women had no abnormality and 915 (23 21") had "diffuse benign disease" requiring no action, and 213 (5-40o) needed further investigation. Ninety-three women (80 of whom attended the review clinic) underwent xeromammography, and 25 had cyst aspirations. A total of 179 women attended the review clinic: 75 did not need immediate treatment, but 21 of these were
recalled at three or six months. Altogether 90 (2 3°') women underwent biopsy (nine bilateral) as a result of initial screening. They included three who had cysts aspirated, 33 who had non-palpable mammographic lesions, and eight who had reattended the review clinic after three to six months. Eleven women were found to have cancer of the breast. After second annual screening 35 women were referred for biopsy (three bilateral) and seven had cancer. One hundred and twenty-five women (137 breasts) therefore had a lesion worthy of biopsy, and 18 were found to have cancer. The primary methods of detection are shown in table III.
TABLE i-Details of patients screened Social class I II III IV V Other
No
(0.)
386 (10) 1069 (27) 1946 (49) 372 (9) 122 (3) 57 (1)
Age 40-44 45-49 50-54 55-59
No (%) 891 1034 1082 945
Marital state
No
No who were nulliparous
(23) (26) (27)
Married Single Divorced or separated
(24)
Widowed
3036 503 152 261
360 462 11 29
BRITISH MEDICAL JOURNAL
177
15 JULY 1978
TABLE iII-Primary methods of detecting a lesion requiring biopsy Findings on biopsy Benign
Malignant
Total
37
1
54 25
9 8
38 63 33
116
18
134
18
137
Clinical Clinical and mammography Mammography Total
3
3
Neither*
Grand total
119
*"Mirror" biopsies of second breast in three patients with cancer.
ACCURACY OF DIAGNOSIS
The preoperative diagnosis was based on a consensus of the findings at initial examination and review clinic and the results of other investigations. The accuracy of this in the 137 biopsied breasts in 125 women is shown in table IV. Of 31 lesions suspected of being malignant 19 proved to be benign and of 106 thought to be benign six proved to be malignant. Two of the seven cancers diagnosed at second screening had, on review of their findings, shown some suspicious signs at first screening.
Preoperative diagnosis Benign
Probably benign
Probably malignant
Normal Mammary dysplasia Dysplasia with atypia Fibroadenoma Other benign Carcinoma: Invasive Non-invasive Total
TABLE v-Comparison of populations and findings of screening programmes
Centre
Malignant
Total 9 60 25 18 7
4 29 11 13 5
4 20 9 4 1
1 9 5 1 1
2 1
3
4 2
6
1 18
65
41
23
8
137
2
Thirty-three women underwent biopsy for non-palpable mammographic lesions. Of 15 with suspicious-looking calcification only one proved to have cancer; of eight with "disturbed architecture," three had cancer; and of 10 with suspicious-looking opacities (two spiculated), four had cancer.
TYPES OF CARCINOMA
Fifteen of the 18 cancers were invasive and six also affected the Of the three non-invasive cancers, two were impalpable and intraduct histologically; the third had a palpable nodule and was a lobular carcinoma in situ. Of the other six impalpable cancers four were early tumours (two measuring under 1 cm) but the other two also affected the axillary nodes, although the actual tumours measured under 1 5 cm.
axillary nodes.
Discussion and conclusions Our response rate of 81 8" 0 to the invitation for screening was much higher than the 6500 in the Health Insurance Plan (HIP) study, New York,4 and the 540o/ in the south Manchester study.5 This was probably due to the fact that the general practitioners signed each letter; many women said that they came only because their doctor asked them to. This high response, ensuring a good sample of normal women, influenced the biopsy rate and cancer detection rate. Our rates were much lower than in the west London6 and south Manchester5 studies, in which self-referred women were admitted and the upper age limit was higher (table V). The equally high
Women screened
Edinburgh
Invited
Ealing6 BUPA9
Invited Invited Self-referred Self-referred Self-referred
(present series) HIP4 Manchester'
TABLE IV-Correlation of preoperative and final diagnoses
Histology
response for annual rescreening (also over 80%) indicates the acceptability of the procedure. Many women appreciated both the opportunity to be screened and the way in which it was conducted. Mammography proved more sensitive than clinical examination in detecting the small number of cancers. The findings of the HIP study suggested that mammography was of no benefit in women under 50.' Our numbers were too small to confirm or refute this suggestion, but six of the 18 cancers found occurred in women under 50 and all were seen on mammography, one being impalpable. As in other studies, a combination of clinical examination and mammography proved more effective than either alone. It is important to repeat clinical examination of the breast with knowledge of positive mammographic findings. When the examiner is alerted to an area of suspicion a clinical abnormality
Age (years)
No of patients
rate per 1000
Cancer rate per 1000 on initial screening
Biopsy
40-60
3952
23-3
2-8
40-64 -50 All ages > 35 All ages
20211 1611 1055 1000 11654
25-2 29 59 7 91 Not stated
2 72 10 6-6 12 6-86*
*Not stated whether initial screening examination only. Reproduced from British Jourtnal of Surgery, 1977, 64, 727, with Edinburgh figures updated.
that was previously overlooked is often discovered. Ten out of 33 cases reported normal at the initial clinical examination were found to have a palpable lesion once the presence of a mammographic abnormality was known. We therefore think that the most effective way of screening well women in this age group is to perform low-dose mammography first followed by history taking and examination by one examiner with simultaneous reporting of mammograms by a second examiner. Then both examiners should discuss the mammograms and clinical findings, and, if necessary, the woman can be re-examined immediately. A firm opinion can therefore be given at a woman's first attendance and a normal result intimated immediately. The number of impalpable lesions detected by mammography indicates the importance of developing techniques for accurate preoperative localisation and for confirming that the lesion has been removed.' Our aim is to remove the lesion with least disturbance. In these minimal lesions preoperative diagnosis by frozen section has little part to play, and histological techniques should be carefully standardised. Should the lesion prove to be cancer on excision biopsy, accurate staging of the patient is an essential part of management and should precede definitive treatment. 8 In the HIP study 10 5%; of cancers detected by screening were non-invasive and 70 50/% did not affect the axillary nodes.7 In our small series three of the 18 cancers were non-invasive and 12 did not affect the nodes. Because we double-checked all examinations and sent out specific appointments and reports to each woman by mail, screening proved expensive. Each screening examination cost about C16-50 and each cancer detected about £6000 exclusive of data processing, surgical and pathological costs. Considerable savings could be achieved by discontinuing thermography and routine double-checking; modifying the appointments system; and introducing the regimen for screening suggested above. In the light of this experience, more invited women are currently being examined by the simplified regimen. Those with no abnormality have been grateful for an immediate report and the clerical burden has been considerably reduced. To date two
178
women have been found to have cancer out of about 600 examined. We are convinced that screening well women contributes to the overall management of breast cancer. At the present rate of detection it is expensive, and efforts must be directed towards making major improvements in imaging techniques and identifying women with a high risk of developing breast cancer. We thank the following people, without whom the study could not have been carried out: Dr S M Shaw and the other clinical medical officers and radiographers; the clerical and other staff, especially Mrs J Anderson and Mrs A Renton; Dr G B Young for help with reporting mammograms; Mr A M C Owen, Mr M C Wilson, and other surgeons who did many of the biopsies; the general practitioners; the staff of the medical computing and statistics unit; the Lothian Health Board and the Scottish Home and Health Department; and Mr G H Mooney of the Health Economics Research Unit for his costing studies.
BRITISH MEDICAL JOURNAL
15 JULY 1978
We also thank the editor of the British J7ournal of Surgery for permission to reproduce table V. Requests for reprints should be sent to Dr Anne Scott, Breast Screening Clinic, Springwell House, Ardmillan Terrace, Edinburgh EH11 2JL.
References 1
Young, G B, British Journal of Radiology, 1974, 47, 811. 2Price, J L, and Butler, P D, X-ray Bulletin, 1971, 19, 3. 3 Owen, A M C, et al, British Journal of Surgery, 1977, 64, 725. Shapiro, S, et al, Proceedings of the National Cancer Conference, 1973, 7, 663. George, W D, et al, British Medical3Journal, 1976, 2, 858. 6 Chamberlain, J, et al, Lancet, 1975, 2, 1026. 7Shapiro, S, Cancer, 1977, 39, 2772. 8 Cant, E L, et al, World Journal of Surgery, 1977, 1, 303. 9 Bailey, A, et al, Clinical Oncology, 1976, 2, 317.
(Accepted 23 February 1978)
Screening for breast cancer Statement by British Breast Group* British Medical3Journal, 1978, 2, 178-180
In 1975 we published our first statement about screening for breast cancer.' Earlier this year we organised a symposium on this subject to review progress in the field, both in Britain and abroad, as a result of which we have updated some of our views. Following the controlled study of benefits of screening for breast cancer by physical examination and mammography, carried out by the Health Insurance Plan (HIP) in New York,2 the American Cancer Society and the National Cancer Institute set up 29 breast cancer detection demonstration programmes in different parts of the United States. These screened some 280 000 women aged 35-74. Subsequently, questions were raised about the safety of x-ray mammography and also about the malignancy of a proportion of the lesions of less than 1 cm in diameter that were detected in the demonstration programmes. A National Institutes of Health-National Cancer Institute panel was therefore set up to review the breast cancer screening controversy. The chairman, Dr S 0 Thier, has recently discussed six key questions arising from the work of that panel, which we think apply as much to this country as to the United States,3 and on which we want to comment.
What is meant by "screening" for breast cancer? Screening means the investigation of women who believe themselves to be free from symptoms and signs of breast disease. Anxiety about the possible hazards of mammography affects particularly these women rather than those who present with a problem that needs evaluation. *Members of the group are: Mr Michael Baum, Mr E A Benson, Mr Roger Blamey, Dr Diana Brinkley, Mr Ian Burn, Dr R D Bulbrook (chairman), Professor Alfred Cuschieri, Dr J A Dossett, Professor A P M Forrest, Mr David George, Dr Huw Gravelle, Professor Keith Griffiths, Dr John Haybittle, Mr John Hayward, Dr Roger King, Dr Peter Maguire, Dr Rosemary Millis, Professor J G Murray, Professor Munro Neville, Dr Trevor Powles, Dr Maureen Roberts (secretary), Dr R D Reubens, Professor R A Sellwood, Professor Roger Short, Dr Helen Stewart, Dr Basil Stoll, and Professor Martin Vessey.
Some centres in Britain, in presenting the results of their screening programmes, combined data about (a) women invited to participate, (b) those who referred themselves (who often suspected an abnormality), and (c) those specifically referred by a doctor for special investigation. This practice was responsible for much of the difficulty experienced in comparing different studies and in assessing the load which the screening of truly asymptomatic women would place on diagnostic and surgical services. What is the evidence that women benefit from screening? Unless a benefit is very large a randomised controlled trial is the only method of evaluation whereby interminable debate can be avoided. For breast cancer screening the HIP study remains the only investigation of this type, although a further randomised controlled trial, in which "single view" mammography is to be evaluated as the sole method of screening, is in progress in Sweden.4 It should be noted that the reduction in breast cancer mortality in the HIP study, which included 30 000 women who were screened and 30 000 controls, was limited to women aged over 50 years. Although experience elsewhere suggests that the results of a single controlled trial may be misleading, we are none the less convinced that early diagnosis of breast cancer is important and that it improves the survival rate. We would like to emphasise that screening programmes in which women refer themselves cannot provide significant further evidence of benefit. Studies in which a serious attempt is made to screen all women of a given age group in a particular geographical area and in which breast cancer mortality is subsequently monitored (both among the screened and among the unscreened) can yield such evidence, especially if data are also collected in control areas. Such a study is in progress in Holland,5 while proposals are in hand to start a similar investigation in Britain. What are the risks of mammography? Information about the carcinogenic effects of ionising radiation on the breast has been obtained from Japanese atomic bomb survivors, from women undergoing fluoroscopy of the chest to
