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Comment on the EUSOMA Consensus Conference on breast screening
ThcBrewt (1995) 4,71-73 0 Pearson Professional Ltd 1995
I---
Correspondence
2. Drug Information Service. 3. Formestane for advanced breast cancer in postmenopausal women. Drug and Therapeutic Bulletin 1993; 31: 25 October. 4. Aromatase inhibitors in malignant disease. Drugs and Ageing 1992; 2: November/December. 5. Focus on Formestane. Drugs 1993; 45.
re: Deep vein thrombosis related to Formestane? Sir, We report a patient who developed a deep venous thrombosis which we believe may have been due to Formestane (4 hydroxyandrostenedione). In 1985 a 68-year-old woman was diagnosed as having a locally advanced carcinoma of the right breast. Surgery was considered inappropriate and she underwent a course of radiotherapy with adjuvant tamoxifen. The tumour regressed initially but began to ulcerate in 1989. A radical mastectomy with rectus abdominis myocutaneous flap reconstruction was performed and the patient was then commenced on medroxyprogesterone acetate. 2 years later (1991) an area of recurrence was excised from the lateral aspect of the scar site. In 1993, she was noted to have recurrence at the medial aspect of the scar in addition to metastatic lymphadenopathy of the left axilla. The patient was converted to intramusclar injections of Formestane (4 hydroxyandrostenedione) 250 mg every 2 weeks. She described some nausea and localized pruritis following the initial injection. Shortly after her third injection she was admitted to hospital with a clinically apparent left calf deep vein thrombosis. She was heparinized and then converted to warfarin for 3 months. A number of side effects have been ascribed to the aromatase inhibitor Formestane. These include nausea, hot flushes, dizziness, rashes and pruritis. Thrombophlebitis is also a recognized adverse effect. However, as far as we are aware, this is the first time that deep venous thrombosis has been associated with the use of Formestane.‘-5 This patient did have a past history of a left iliofemoral DVT which occured in the immediate postoperative period after her radical mastectomy and reconstruction. It remains to be seen whether a past history of DVT will emerge as a contraindication to the use of Formestane. This case has been reported to the Committee on Safety on Medicine.
re: Comment on the EUSOMA Consensus Conference on breast screening
Sir, After a great deal of confusion about screening it was satisfying to see an official article that expresses the current status of screening clearly and briefly. Perhaps it would have been better to clarify that: (1) the paper was related entirely to breast screening by mammography and did not relate to mammography of symptomatic patients; (2) screening is not diagnosis and (3) a screening programme for self referred women, even if asymptomatic, has costs and targets which are different from those of symptomatic women. The main current debate centres on the confusion between protocols used in a screening programme and those used for self referred women, symptomatic or asymptomatic. Many think that the same protocols can be used for both groups. There remains confusion about the advice given to women regarding the age at which they should start screening, the interval between screens and the technique or techniques used. It must be made clear that screening has one goal and that is to select patients with an abnormal test who need further investigation and not to diagnose patients and for this reason, other than in a screening programme, mammography should always be performed in association with other diagnostic procedures such as physical examination, ultrasound and fine needle aspiration cytology. It is our view that mammography performed in association with these other techniques performed in women under 50 can give better results than standard screening mammography. We use the term ‘clinical mammography’ for these women which includes not only mammography but combines this with other procedures as appropriate. According to a Directive of the Committee of the Senology section of the Italian Society of Radiology (the SIRM), the only point of contention with the list of recommendations relates to conclusion 4 which states that younger women who request mammography should have it performed only after informing them of the uncertainty and advising them of the possible consequences. It is not clear whether the young women referred to are those over 40 years of age or whether they are younger women. The main problems with this statement is that this could lead people to believe that
P. Williams M. E. Foster Department of Surgery East Glamorgan General Hospital Church Village Nr Pontypridd UK
References 1. British
National
Formulary
1993. Pharmaceutical
Press. 71
72
The Breast
because of concern about the accuracy of mammography in these young women, that alternative diagnostic tests should be used. Would it not have been better to state that these women must be informed about the current doubts of the benefits of screening in this age group. With regard to women between the ages of 40 and 50 years, it should be highlighted that the EUSOMA paper clearly states that (1) the split between women over 50 years and those younger is arbritary; (2) the primary analyses of screening studies relates to all randomized women and there was no division into different age groups (these studies have demonstrated that screening reduces mortality in the total group of women screened); (3) at present there is an indication that the reduction in mortality is smaller in women under the age of 50, although the data in this group are limited and the results are inconclusive. The screening of women under 50 years is widespread in Europe and there is a perception of benefit in this age group despite the scientific uncertainty. It was pointed out that it could be the prolonged interval between screening examinations rather than lower sensitivity in younger women that explains why currently, mammographic screening has not been shown to be of any benefit in this younger age group. Having assessedthese points the evaluation Committee indicates that mammographic screening in women between the age of 40 and 50 should only take place as part of a research programme. The UICC in fact reached the same conclusion in the meeting on ‘Breast cancer screening in premenopausal women in developed countries’ held in Geneva on 29 September - 1 October 1993. The problem with this is that few young women have been included in the various screening trials and there is the possibility that mammography performed by the radiologist, using a clinical approach in a personalized way, can achieve better results than standard screening mammography. Furthermore it was pointed out in the EUSOMA report that cancer growth in younger women may be more rapid and one reason mammographic screening has not currently been shown to be effective in this age group could be the prolonged interval between screens and could be unrelated to the lower sensitivity of mammography in this age group. We would like to praise the Commission for underlying the negative effects of screening and the need for a carefully designed and planned programme. Unfortunately, these aspects of screening are often underestimated. C. di Maggio President of the Senology Section of SIRM (Italian Society of Radiology) Instituto di Radiologi dell’Universita via Giustiniani 2-35 128 Padova Italy
Reply We are pleased that Dr di Maggio and his colleagues
were satisfied with our EUSOMA report. We agree with their views. Our remarks on mammographic screening should not be taken to imply that screening women under 50 years of age can be carried out justifiably by other means. Screening women under the age of 50 by any means is of unknown efficacy and safety. Safety in this context includes the harm arising from unnecessary medical intervention, prompted by screening. In referring to ‘younger women’, we mean any woman under 50 years, and pointed out that the split between 50 or more and those who were younger was arbitrary. N. J. Wald A. Hackshaw J. Chamberlain Department of Environmental and Preventive Medicine The Medical College of St Bartholomew’s Hospital (University of London) Charterhouse Square London EClM 6BQ UK
re: Gestrinone in mastalgia: a randomized double bind placebo controlled trial (The Breast 1994; 3: 90-93) Sir, We read with interest the paper of Dr Stein and coworkers’ about gestrinone in mastalgia. I would like to raise two points: Firstly, 2 years ago we published an article in The Lancet (January 25) reporting a study of gestrinone in cyclical breast pain.* It is surprising that the British authors missed this article in what is one of the UK’s leading journals. Citation of relevant literature is more than a mere scientific obligation. Secondly, the severity of the pain as measured by the visual analogue scale and the heterogeneity of patients studied question that the indications for treating some of these patients at all. The fact that the drug relieves breast pain is not sufficient indication for its use. Are we to conclude from Dr Stein’s paper that we should now treat 62-year-old women with any breast pain with gestrinone? It is known that more than half the women who present with breast pain do not wish medical treatment. Did the authors ask their patients about whether they wished treatment? Although Dr Stein and his colleagues were correct in stating that we do not know the cause of either cyclical or non-cyclical mastalgia, we do know a number of differential diagnoses3 which should be excluded before treating breast pain. Did the authors exclude breast cancer and coronary heart disease in their patients, particularly in those over 50 years of age? During the last few years valuable attempts have been made to classify breast pain3 and benign breast disorders.4v5The paper by Stein and colleagues fails to help us in understanding the nature of breast pain and it encourages us to treat any discomfort in women’ breasts with gestrinone. Mastalgia may be a disease in its own
I---
Correspondence
2. Drug Information Service. 3. Formestane for advanced breast cancer in postmenopausal women. Drug and Therapeutic Bulletin 1993; 31: 25 October. 4. Aromatase inhibitors in malignant disease. Drugs and Ageing 1992; 2: November/December. 5. Focus on Formestane. Drugs 1993; 45.
re: Deep vein thrombosis related to Formestane? Sir, We report a patient who developed a deep venous thrombosis which we believe may have been due to Formestane (4 hydroxyandrostenedione). In 1985 a 68-year-old woman was diagnosed as having a locally advanced carcinoma of the right breast. Surgery was considered inappropriate and she underwent a course of radiotherapy with adjuvant tamoxifen. The tumour regressed initially but began to ulcerate in 1989. A radical mastectomy with rectus abdominis myocutaneous flap reconstruction was performed and the patient was then commenced on medroxyprogesterone acetate. 2 years later (1991) an area of recurrence was excised from the lateral aspect of the scar site. In 1993, she was noted to have recurrence at the medial aspect of the scar in addition to metastatic lymphadenopathy of the left axilla. The patient was converted to intramusclar injections of Formestane (4 hydroxyandrostenedione) 250 mg every 2 weeks. She described some nausea and localized pruritis following the initial injection. Shortly after her third injection she was admitted to hospital with a clinically apparent left calf deep vein thrombosis. She was heparinized and then converted to warfarin for 3 months. A number of side effects have been ascribed to the aromatase inhibitor Formestane. These include nausea, hot flushes, dizziness, rashes and pruritis. Thrombophlebitis is also a recognized adverse effect. However, as far as we are aware, this is the first time that deep venous thrombosis has been associated with the use of Formestane.‘-5 This patient did have a past history of a left iliofemoral DVT which occured in the immediate postoperative period after her radical mastectomy and reconstruction. It remains to be seen whether a past history of DVT will emerge as a contraindication to the use of Formestane. This case has been reported to the Committee on Safety on Medicine.
re: Comment on the EUSOMA Consensus Conference on breast screening
Sir, After a great deal of confusion about screening it was satisfying to see an official article that expresses the current status of screening clearly and briefly. Perhaps it would have been better to clarify that: (1) the paper was related entirely to breast screening by mammography and did not relate to mammography of symptomatic patients; (2) screening is not diagnosis and (3) a screening programme for self referred women, even if asymptomatic, has costs and targets which are different from those of symptomatic women. The main current debate centres on the confusion between protocols used in a screening programme and those used for self referred women, symptomatic or asymptomatic. Many think that the same protocols can be used for both groups. There remains confusion about the advice given to women regarding the age at which they should start screening, the interval between screens and the technique or techniques used. It must be made clear that screening has one goal and that is to select patients with an abnormal test who need further investigation and not to diagnose patients and for this reason, other than in a screening programme, mammography should always be performed in association with other diagnostic procedures such as physical examination, ultrasound and fine needle aspiration cytology. It is our view that mammography performed in association with these other techniques performed in women under 50 can give better results than standard screening mammography. We use the term ‘clinical mammography’ for these women which includes not only mammography but combines this with other procedures as appropriate. According to a Directive of the Committee of the Senology section of the Italian Society of Radiology (the SIRM), the only point of contention with the list of recommendations relates to conclusion 4 which states that younger women who request mammography should have it performed only after informing them of the uncertainty and advising them of the possible consequences. It is not clear whether the young women referred to are those over 40 years of age or whether they are younger women. The main problems with this statement is that this could lead people to believe that
P. Williams M. E. Foster Department of Surgery East Glamorgan General Hospital Church Village Nr Pontypridd UK
References 1. British
National
Formulary
1993. Pharmaceutical
Press. 71
72
The Breast
because of concern about the accuracy of mammography in these young women, that alternative diagnostic tests should be used. Would it not have been better to state that these women must be informed about the current doubts of the benefits of screening in this age group. With regard to women between the ages of 40 and 50 years, it should be highlighted that the EUSOMA paper clearly states that (1) the split between women over 50 years and those younger is arbritary; (2) the primary analyses of screening studies relates to all randomized women and there was no division into different age groups (these studies have demonstrated that screening reduces mortality in the total group of women screened); (3) at present there is an indication that the reduction in mortality is smaller in women under the age of 50, although the data in this group are limited and the results are inconclusive. The screening of women under 50 years is widespread in Europe and there is a perception of benefit in this age group despite the scientific uncertainty. It was pointed out that it could be the prolonged interval between screening examinations rather than lower sensitivity in younger women that explains why currently, mammographic screening has not been shown to be of any benefit in this younger age group. Having assessedthese points the evaluation Committee indicates that mammographic screening in women between the age of 40 and 50 should only take place as part of a research programme. The UICC in fact reached the same conclusion in the meeting on ‘Breast cancer screening in premenopausal women in developed countries’ held in Geneva on 29 September - 1 October 1993. The problem with this is that few young women have been included in the various screening trials and there is the possibility that mammography performed by the radiologist, using a clinical approach in a personalized way, can achieve better results than standard screening mammography. Furthermore it was pointed out in the EUSOMA report that cancer growth in younger women may be more rapid and one reason mammographic screening has not currently been shown to be effective in this age group could be the prolonged interval between screens and could be unrelated to the lower sensitivity of mammography in this age group. We would like to praise the Commission for underlying the negative effects of screening and the need for a carefully designed and planned programme. Unfortunately, these aspects of screening are often underestimated. C. di Maggio President of the Senology Section of SIRM (Italian Society of Radiology) Instituto di Radiologi dell’Universita via Giustiniani 2-35 128 Padova Italy
Reply We are pleased that Dr di Maggio and his colleagues
were satisfied with our EUSOMA report. We agree with their views. Our remarks on mammographic screening should not be taken to imply that screening women under 50 years of age can be carried out justifiably by other means. Screening women under the age of 50 by any means is of unknown efficacy and safety. Safety in this context includes the harm arising from unnecessary medical intervention, prompted by screening. In referring to ‘younger women’, we mean any woman under 50 years, and pointed out that the split between 50 or more and those who were younger was arbitrary. N. J. Wald A. Hackshaw J. Chamberlain Department of Environmental and Preventive Medicine The Medical College of St Bartholomew’s Hospital (University of London) Charterhouse Square London EClM 6BQ UK
re: Gestrinone in mastalgia: a randomized double bind placebo controlled trial (The Breast 1994; 3: 90-93) Sir, We read with interest the paper of Dr Stein and coworkers’ about gestrinone in mastalgia. I would like to raise two points: Firstly, 2 years ago we published an article in The Lancet (January 25) reporting a study of gestrinone in cyclical breast pain.* It is surprising that the British authors missed this article in what is one of the UK’s leading journals. Citation of relevant literature is more than a mere scientific obligation. Secondly, the severity of the pain as measured by the visual analogue scale and the heterogeneity of patients studied question that the indications for treating some of these patients at all. The fact that the drug relieves breast pain is not sufficient indication for its use. Are we to conclude from Dr Stein’s paper that we should now treat 62-year-old women with any breast pain with gestrinone? It is known that more than half the women who present with breast pain do not wish medical treatment. Did the authors ask their patients about whether they wished treatment? Although Dr Stein and his colleagues were correct in stating that we do not know the cause of either cyclical or non-cyclical mastalgia, we do know a number of differential diagnoses3 which should be excluded before treating breast pain. Did the authors exclude breast cancer and coronary heart disease in their patients, particularly in those over 50 years of age? During the last few years valuable attempts have been made to classify breast pain3 and benign breast disorders.4v5The paper by Stein and colleagues fails to help us in understanding the nature of breast pain and it encourages us to treat any discomfort in women’ breasts with gestrinone. Mastalgia may be a disease in its own