359 and isoniazid 900 mg, rifampicin 600 mg, and pyridoxine 10 mg twice weekly for 15 months. The patients’ progress was monitored with regular clinical assessment, including inquiry about drug acceptability and with radiographs and sputum examinaside-effects, tion. In addition, monthly specimens of serum were examined for rifampicin antibodies, and when these were present platelets were counted before and after the next rifampicin dose. The regimen proved to be very acceptable, and all patients rapidly improved. No relapses have occurred during a follow-up period ranging from 20 to 43 months. Rifampicin-dependent antibodies, reported in 10 patients (20%), appeared from 1 to 12 months after starting intermittent treatment. No antibodies were reported during daily treatment. One patient with rifampicin-dependent antibodies developed a sharp "flulike" syndrome after 11months of twice-weekly treatment, and the drug was replaced by streptomycin. Platelet-counts did not fall significantly in any of the patients with rifampicin-de-
together
pendent antibodies. Since this low incidence of side-effects seems to be concentrated in the later months of treatment, it is probable that they will be even less frequent during the rifampicin-containing regimens of shorter duration now becoming acceptable. But proper supervision of drug taking becomes increasingly important as the duration of intermittent treatment is reduced: missing already infrequent doses may not only reduce the total treatment but lengthen the gaps between doses sufficiently to render treatment ineffective. GRAHAM W. POOLE Departments of Medicine and Hæmatology, PETER STRADLING Hammersmith Hospital, London W12 0HS. SHEILA WORLLEDGE
SCREENING FOR TUBERCULOSIS IN PATIENTS WITH PNEUMOCONIOSIS
SIR,-Dr Gordon’ suggests screening for tuberculosis in patients with pneumoconiosis, and Dr Sayedrecommends prolonged follow-up of such patients. These measures may lead to the detection of cases of tuberculosis in this acknowledged high-risk group, but they will not prevent tuberculosis from occurring nor infection from being transmitted before diagnosis. In the United States the Public Health Service Center for Disease Control, the American Thoracic Society, and the American Lung Association have for many years recommended the administration of isoniazid preventive therapy to infected persons with pneumoconiosis, particularly silicosis.3 It is our feeling that scarce health resources are better spent on preventive measures which result in a favourable outcome for the patient rather than on examinations which detect an unfavourable outcome which might well have been prevented. Tuberculosis Control Division, Bureau of State Services, Public Health Service Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
LAURENCE S. FARER
SCREENING FOR BREAST CANCER
Sirhave read with interest the reports by Thomas4 and Chamberlain et al.1Ihave been screening well women for early breast cancer since 1967, and perhaps I can satisfy some of the queries raised by Smith and
Leek,’
and Alderson.7
1 Gordon, N. S. Lancet, 1975, ii, 976. 2 Sayed, Q. A. ibid. p. 1212. 3 American Thoracic Society Am. Rev. Res. Dis. 1974, 4 Thomas, B. Lancet, 1975, ii, 914. 5 Chamberlain, J., Ginks, S., Rogers, P., Nathan, B. I ibid. p. 1026. 6 Smith, A., Leck, I. ibid. p. 1142. 7 Alderson, M. ibid. p. 1143.
110, no. 3. E., Price, J. L., Burn,
For screening I use detailed history, clinical examination, thermography, and mammography*a In self-selected well women aged 35-75 there have been 7-6/1000 confirmed cancers, 6-2/1000 being preclinical. In high-risk well women in the same age-group, the pick-up rate has been 24-5/1000, 19- 3/1000 being preclinical. Women considered to be at higher than average risk are those who have had a previous abnormal thermogram or equivocal mammogram, those who have maternal family history of breast cancer, childless women, those of low parity and those whose first viable child was born after the age of 35, those with a past history of a benign breast lesion or knotty fibrocystic breasts, and women with a late menopause. I consider the result to be a false negative if a clinical lesion develops within 12 months of a negative screening test. My false-negative rate for screening by all modalities is 3-33%. If screening is to be a practical proposition, the false-negative rate at 12 months must be acceptable--6 months is too soon. Of the women referred for biopsy with a diagnosis of cancer 58% had proven cancer (43% in situ, 57% invasive), 20.9% a possibly premalignant lesion, 18-9% a benign lesion, and 2.2% a
negative biopsy.
I consider that screening should begin at 35 years. 52% of my well women have been in the age-group 35-49, and from this group have come 61.4% of the total yield of cancers. There has been no significant relationship between the stage of the lesion (i.e., in situ or invasive) and the age of the woman. I wish to emphasise that these figures are for symptom-free women; the only "symptom" acceptable in a well women is
premenstrual aching and tenderness. In this area of North-East England there is an increasing degree of self-selection of a high-risk group-in 1969, 31% of the self-selected group fell into the high-risk category, by 1971 this proportion was 38.9%, and it was 45.5% in 1972, 36.6% in 1973, 50.7% in 1974, and 59.7% in 1975. This is probably because women have become more knowledgeable about highrisk factors and know that I wish to concentrate on them. Alderson4 asks, does screening work? It is only by screening a fairly large group of women by modern techniques and being patient over the next 10 years at least, that this question can be answered. 5-year survival figures are not valid because of the lead-time gained by screening. With my experience I am cautiously optimistic. All the women found to have a non-palpable lesion remain fit and well-some now for 8 years. "The investment of effort in screening" is surely balanced by this and also the fact that those women have had relatively minor surgical procedures (i.e., a simple or modified radical mastectomy) and have avoided ablative surgery, deep X-ray therapy, hormonal therapy, chemotherapy, and immunotherapy. After a negative initial screening, high-risk women are offered annual review; the others are asked to reapply if they want a further appointment, and they are seen on average at 30-month intervals. During the past 6 years, the pick-up rate on annual review of high-risk women has averaged 8-3/1000. I consider this justifies annual re-screening of a high-risk group.
77.4% of cancers have been in women with high-risk factors in their history, with or without an abnormal thermogram; 16.6% have been in women without such a history but who had an abnormal thermogram at their initial screening. While an abnormal thermogram is by no means specific for malignancy, I have found it to be a major risk factor. Only 6% of my total cancers have occurred in women with no risk factor. Since resources (financial and trained personnel) are limited, I have decided that the yield on re-screening of women not at high risk is too low to justifiy re-screening on an annual basis, if at all. Women’s Cancer Detection Society Breast Department of Gynæcological Oncology, Queen Elizabeth Hospital, Gateshead NE9 6SX.
8.
Clinic,
Stark, A. M., Way, S. Cancer, 1974, 33, 1664, 1671.
AGNES M. STARK
together
pendent antibodies. Since this low incidence of side-effects seems to be concentrated in the later months of treatment, it is probable that they will be even less frequent during the rifampicin-containing regimens of shorter duration now becoming acceptable. But proper supervision of drug taking becomes increasingly important as the duration of intermittent treatment is reduced: missing already infrequent doses may not only reduce the total treatment but lengthen the gaps between doses sufficiently to render treatment ineffective. GRAHAM W. POOLE Departments of Medicine and Hæmatology, PETER STRADLING Hammersmith Hospital, London W12 0HS. SHEILA WORLLEDGE
SCREENING FOR TUBERCULOSIS IN PATIENTS WITH PNEUMOCONIOSIS
SIR,-Dr Gordon’ suggests screening for tuberculosis in patients with pneumoconiosis, and Dr Sayedrecommends prolonged follow-up of such patients. These measures may lead to the detection of cases of tuberculosis in this acknowledged high-risk group, but they will not prevent tuberculosis from occurring nor infection from being transmitted before diagnosis. In the United States the Public Health Service Center for Disease Control, the American Thoracic Society, and the American Lung Association have for many years recommended the administration of isoniazid preventive therapy to infected persons with pneumoconiosis, particularly silicosis.3 It is our feeling that scarce health resources are better spent on preventive measures which result in a favourable outcome for the patient rather than on examinations which detect an unfavourable outcome which might well have been prevented. Tuberculosis Control Division, Bureau of State Services, Public Health Service Center for Disease Control, Atlanta, Georgia 30333, U.S.A.
LAURENCE S. FARER
SCREENING FOR BREAST CANCER
Sirhave read with interest the reports by Thomas4 and Chamberlain et al.1Ihave been screening well women for early breast cancer since 1967, and perhaps I can satisfy some of the queries raised by Smith and
Leek,’
and Alderson.7
1 Gordon, N. S. Lancet, 1975, ii, 976. 2 Sayed, Q. A. ibid. p. 1212. 3 American Thoracic Society Am. Rev. Res. Dis. 1974, 4 Thomas, B. Lancet, 1975, ii, 914. 5 Chamberlain, J., Ginks, S., Rogers, P., Nathan, B. I ibid. p. 1026. 6 Smith, A., Leck, I. ibid. p. 1142. 7 Alderson, M. ibid. p. 1143.
110, no. 3. E., Price, J. L., Burn,
For screening I use detailed history, clinical examination, thermography, and mammography*a In self-selected well women aged 35-75 there have been 7-6/1000 confirmed cancers, 6-2/1000 being preclinical. In high-risk well women in the same age-group, the pick-up rate has been 24-5/1000, 19- 3/1000 being preclinical. Women considered to be at higher than average risk are those who have had a previous abnormal thermogram or equivocal mammogram, those who have maternal family history of breast cancer, childless women, those of low parity and those whose first viable child was born after the age of 35, those with a past history of a benign breast lesion or knotty fibrocystic breasts, and women with a late menopause. I consider the result to be a false negative if a clinical lesion develops within 12 months of a negative screening test. My false-negative rate for screening by all modalities is 3-33%. If screening is to be a practical proposition, the false-negative rate at 12 months must be acceptable--6 months is too soon. Of the women referred for biopsy with a diagnosis of cancer 58% had proven cancer (43% in situ, 57% invasive), 20.9% a possibly premalignant lesion, 18-9% a benign lesion, and 2.2% a
negative biopsy.
I consider that screening should begin at 35 years. 52% of my well women have been in the age-group 35-49, and from this group have come 61.4% of the total yield of cancers. There has been no significant relationship between the stage of the lesion (i.e., in situ or invasive) and the age of the woman. I wish to emphasise that these figures are for symptom-free women; the only "symptom" acceptable in a well women is
premenstrual aching and tenderness. In this area of North-East England there is an increasing degree of self-selection of a high-risk group-in 1969, 31% of the self-selected group fell into the high-risk category, by 1971 this proportion was 38.9%, and it was 45.5% in 1972, 36.6% in 1973, 50.7% in 1974, and 59.7% in 1975. This is probably because women have become more knowledgeable about highrisk factors and know that I wish to concentrate on them. Alderson4 asks, does screening work? It is only by screening a fairly large group of women by modern techniques and being patient over the next 10 years at least, that this question can be answered. 5-year survival figures are not valid because of the lead-time gained by screening. With my experience I am cautiously optimistic. All the women found to have a non-palpable lesion remain fit and well-some now for 8 years. "The investment of effort in screening" is surely balanced by this and also the fact that those women have had relatively minor surgical procedures (i.e., a simple or modified radical mastectomy) and have avoided ablative surgery, deep X-ray therapy, hormonal therapy, chemotherapy, and immunotherapy. After a negative initial screening, high-risk women are offered annual review; the others are asked to reapply if they want a further appointment, and they are seen on average at 30-month intervals. During the past 6 years, the pick-up rate on annual review of high-risk women has averaged 8-3/1000. I consider this justifies annual re-screening of a high-risk group.
77.4% of cancers have been in women with high-risk factors in their history, with or without an abnormal thermogram; 16.6% have been in women without such a history but who had an abnormal thermogram at their initial screening. While an abnormal thermogram is by no means specific for malignancy, I have found it to be a major risk factor. Only 6% of my total cancers have occurred in women with no risk factor. Since resources (financial and trained personnel) are limited, I have decided that the yield on re-screening of women not at high risk is too low to justifiy re-screening on an annual basis, if at all. Women’s Cancer Detection Society Breast Department of Gynæcological Oncology, Queen Elizabeth Hospital, Gateshead NE9 6SX.
8.
Clinic,
Stark, A. M., Way, S. Cancer, 1974, 33, 1664, 1671.
AGNES M. STARK
