1101 have time to
to consolidate? There is a danger that this approach gut-hormone research may outgrow its strength.
Selly Oak Hospital, Birmingham B29 6JD Frenchay Hospital, Bristol
Department of Medicine, Bristol Royal Infirmary
T. S. LOW-BEER
R. F. HARVEY K. W. HEATON ALAN READ
explain the failure to detect raised with argentaffin carcinoids. Departments of Histology, Pharmacology, and Medicine, University of Lund, Lund, Sweden Department of Bioorganic Chemistry,
College of Pharmacy, Shizuoka, Japan
serum-motilin in
patients
F. SUNDLER
J. ALUMETS R. HÅKANSON K. SJÖLUND N. YANAIHARA
ADJUVANT HORMONO-CHEMOTHERAPY IN OPERABLE BREAST CANCER MOTILIN AND CARCINOID TUMOURS
SIR,-Modlin et al.’ expressed surprise at their failure to find raised serum-motilin levels in patients with intestinal argentaffin carcinoid tumours. The rationale behind such a search was a previous proposal that motilin is produced by a population of (5-H.T.-storing) enterochromaffin cells,2.3 which give rise to argentaffin carcinoids. Substance P (or a closely related peptide) occurs in a population of enterochromaffin
SiR,-The results of adjuvant chemotherapy in large randomised series have so far shown delay in recurrence, but no improvement in survival-rate in the group receiving additive treatment. 1,2 On the other hand, prospects for adjuvant endocrine therapy have been boosted by the recent report of an increased 10-year survival rate in a randomised study, from X-ray castration and prednisone therapy in premenopausal women aged over 45.3 It is important that new clinical trials should assess the possible added benefit from the combination of cytotoxic and endocrine therapy compared with their separate effects. A U.K. multicentre trial of hormono-chemotherapy in early poor-risk breast carcinoma has set up in four limbs, comparing a control group receiving no adjuvant therapy with a polychemotherapy group (cyclophosphamide, fluorouracil, and methotrexate), a tamoxifen therapy group, and a group treated by both modalities. This trial differs from existing trials in that: (1) Tamoxifen therapy is prolonged for 24 months and cytotoxic therapy for 18 months (6 months intravenous followed by 12 months oral). Bonadonna et al.1 noted that failures of cytotoxic therapy began
appear after the end of their 12 months’ course. (2) The combination is given concurrently and not sequentially. Cavalli et al.4 have shown that the results of combination tamoxifen/ polychemotherapy in postmenopausal advanced breast cancer are better than when they are given sequentially. A similar observation has been made on the results of combination oophorectomy/polychemotherapy in premenopausal advanced breast cancer.5 (3) Tamoxifen dosage is 20 mg twice a day. A large trial in postmenopausal advanced breast cancer showed the response-rate to this dosage to be significantly superior to that of 10 mg twice a day.6 (4) A control untreated group is retained in order to assess the efficacy of each method separately. We do not accept that withholding adjuvant treatment in operated breast cancer is unethical. to
Human duodenum:
formaldehyde-vapour-fixed biopsy speci-
men.
Left: enterochromaffin cell displaying yellow formaldehyde-induced fluorescence due to its content of 5-H.T. Right: same section after motilin immunoperoxidase staining (PAP technique). The motilin cell (arrow) is devoid of 5-H.T., while the enterochromaffin cell is devoid of motilin immunoreactivity (xabout 270).
cells4,5-and in a proportion of gut argentaffin carcinoids as well—but it is by no means certain that motilin does.8’By immunohistochemistry, with a previously characterised antiserum against synthetic motilin,9 we have found motilin cells to be distinct from enterochromaffin cells (see figure). Not unexpectedly, therefore, we have failed to find motilin-immunoreactive cells in 5-H.T.-storing gut carcinoids. The fact that motilin cells are distinct from enterochromaffin cells may 1. Modlin, I. M., Bloom, S. R., Christofides, N. Lancet, 1977, ii, 979. 2. Polak, J. M., Pearse, A. G. E., Heath, C. M. Gut, 1975, 16, 225. 3. Pearse, A. G. E. Scand. J. Gastroent. 1976, suppl. 39, p. 35. 4. Heitz, Ph., Polak, J. M., Timson, C. M., Pearse, A. G. E. Histochemistry,
1976, 49, 343. 5. Sundler, F., Alumets, J., Hakanson, R. Acta physiol. scand. 1977, suppl. 452, p.121. 6. Håkanson, R., Bengmark, S., Brodin, E., Ingemansson, S., Larsson, L.-I., Nilsson, G., Sundler, F. in Substance P; p.55. New York, 1977. 7. Alumets, J., Håkanson, R., Ingemansson, S., Sundler, F. Histochemistry, 1977, 52, 217. 8. Forssmann, W. G., Yanaihara, N., Helmstaedter, V., Grube, D. Scand. J. Gastroent. 1976, suppl. 39, p. 43. 9. Yanaihara, C., Sato, H., Yanaihara, N., Naruse, S., Forssmann, W. G., Helmstaedter, V., Fujita, T., Yamaguchi, K., Abe, K. in Proceedings of an international symposium on Gut Hormone Pathology (Rome, 1977) (in the press.)
Improvement in the treatment of breast cancer can come only from cooperative clinical studies, and we would therefore welcome any group of clinicians who wish to participate in this important randomised trial, if they have facilities for and experience in the monitoring of cytotoxic chemotherapy in cancer. Histological demonstration of invaded axillary nodes is mandatory, but there are no stipulations as to the local treatment by surgery or irradiation so long as the intention is curative. Further details can be obtained from Dr F. Senanayake, Departof Radiotherapy & Oncology, Royal Free Hospital, Pond Street, London NW3.
ment
Newcastle General
Westminster Hospital, London
R. WILSON I. W. F. HANHAM
The London
G. MAIR
Hospital
Hospital Royal Victoria Hospital, Folkestone Folkestone Hospital Hammersmith Hospital, London Royal Free and St. Thomas’ Hospitals, London Royal Free Hospital
Royal Free Hospital Royal Free and Royal Northern Hospitals, London
S. R. DRAKE C. D. DERRY C. MCKENZIE B. A. STOLL E. BOESEN D. B. L. SKEGGS F. SENANAYAKE
1. Fisher, B., and others, New Engl. J. Med. 1975, 292, 117 2. Bonadonna, G., and others, Cancer, 1977, 39, suppl. p. 2905. 3. Meakin, J. W., and others, in Adjuvant Therapy of Cancer (edited by S. E. Salmon and S. E. Jones), p. 95. Amsterdam, 1977. 4. Cavalli, F., and others, 4th int. Congr. Chemother. 1977, abstr. 510, 615. 5. Ahmann, D. L., and others, New Engl. J. Med., 297, 356 6. Ward, H. W. C. Br. med. J. 1973, i, 13
to consolidate? There is a danger that this approach gut-hormone research may outgrow its strength.
Selly Oak Hospital, Birmingham B29 6JD Frenchay Hospital, Bristol
Department of Medicine, Bristol Royal Infirmary
T. S. LOW-BEER
R. F. HARVEY K. W. HEATON ALAN READ
explain the failure to detect raised with argentaffin carcinoids. Departments of Histology, Pharmacology, and Medicine, University of Lund, Lund, Sweden Department of Bioorganic Chemistry,
College of Pharmacy, Shizuoka, Japan
serum-motilin in
patients
F. SUNDLER
J. ALUMETS R. HÅKANSON K. SJÖLUND N. YANAIHARA
ADJUVANT HORMONO-CHEMOTHERAPY IN OPERABLE BREAST CANCER MOTILIN AND CARCINOID TUMOURS
SIR,-Modlin et al.’ expressed surprise at their failure to find raised serum-motilin levels in patients with intestinal argentaffin carcinoid tumours. The rationale behind such a search was a previous proposal that motilin is produced by a population of (5-H.T.-storing) enterochromaffin cells,2.3 which give rise to argentaffin carcinoids. Substance P (or a closely related peptide) occurs in a population of enterochromaffin
SiR,-The results of adjuvant chemotherapy in large randomised series have so far shown delay in recurrence, but no improvement in survival-rate in the group receiving additive treatment. 1,2 On the other hand, prospects for adjuvant endocrine therapy have been boosted by the recent report of an increased 10-year survival rate in a randomised study, from X-ray castration and prednisone therapy in premenopausal women aged over 45.3 It is important that new clinical trials should assess the possible added benefit from the combination of cytotoxic and endocrine therapy compared with their separate effects. A U.K. multicentre trial of hormono-chemotherapy in early poor-risk breast carcinoma has set up in four limbs, comparing a control group receiving no adjuvant therapy with a polychemotherapy group (cyclophosphamide, fluorouracil, and methotrexate), a tamoxifen therapy group, and a group treated by both modalities. This trial differs from existing trials in that: (1) Tamoxifen therapy is prolonged for 24 months and cytotoxic therapy for 18 months (6 months intravenous followed by 12 months oral). Bonadonna et al.1 noted that failures of cytotoxic therapy began
appear after the end of their 12 months’ course. (2) The combination is given concurrently and not sequentially. Cavalli et al.4 have shown that the results of combination tamoxifen/ polychemotherapy in postmenopausal advanced breast cancer are better than when they are given sequentially. A similar observation has been made on the results of combination oophorectomy/polychemotherapy in premenopausal advanced breast cancer.5 (3) Tamoxifen dosage is 20 mg twice a day. A large trial in postmenopausal advanced breast cancer showed the response-rate to this dosage to be significantly superior to that of 10 mg twice a day.6 (4) A control untreated group is retained in order to assess the efficacy of each method separately. We do not accept that withholding adjuvant treatment in operated breast cancer is unethical. to
Human duodenum:
formaldehyde-vapour-fixed biopsy speci-
men.
Left: enterochromaffin cell displaying yellow formaldehyde-induced fluorescence due to its content of 5-H.T. Right: same section after motilin immunoperoxidase staining (PAP technique). The motilin cell (arrow) is devoid of 5-H.T., while the enterochromaffin cell is devoid of motilin immunoreactivity (xabout 270).
cells4,5-and in a proportion of gut argentaffin carcinoids as well—but it is by no means certain that motilin does.8’By immunohistochemistry, with a previously characterised antiserum against synthetic motilin,9 we have found motilin cells to be distinct from enterochromaffin cells (see figure). Not unexpectedly, therefore, we have failed to find motilin-immunoreactive cells in 5-H.T.-storing gut carcinoids. The fact that motilin cells are distinct from enterochromaffin cells may 1. Modlin, I. M., Bloom, S. R., Christofides, N. Lancet, 1977, ii, 979. 2. Polak, J. M., Pearse, A. G. E., Heath, C. M. Gut, 1975, 16, 225. 3. Pearse, A. G. E. Scand. J. Gastroent. 1976, suppl. 39, p. 35. 4. Heitz, Ph., Polak, J. M., Timson, C. M., Pearse, A. G. E. Histochemistry,
1976, 49, 343. 5. Sundler, F., Alumets, J., Hakanson, R. Acta physiol. scand. 1977, suppl. 452, p.121. 6. Håkanson, R., Bengmark, S., Brodin, E., Ingemansson, S., Larsson, L.-I., Nilsson, G., Sundler, F. in Substance P; p.55. New York, 1977. 7. Alumets, J., Håkanson, R., Ingemansson, S., Sundler, F. Histochemistry, 1977, 52, 217. 8. Forssmann, W. G., Yanaihara, N., Helmstaedter, V., Grube, D. Scand. J. Gastroent. 1976, suppl. 39, p. 43. 9. Yanaihara, C., Sato, H., Yanaihara, N., Naruse, S., Forssmann, W. G., Helmstaedter, V., Fujita, T., Yamaguchi, K., Abe, K. in Proceedings of an international symposium on Gut Hormone Pathology (Rome, 1977) (in the press.)
Improvement in the treatment of breast cancer can come only from cooperative clinical studies, and we would therefore welcome any group of clinicians who wish to participate in this important randomised trial, if they have facilities for and experience in the monitoring of cytotoxic chemotherapy in cancer. Histological demonstration of invaded axillary nodes is mandatory, but there are no stipulations as to the local treatment by surgery or irradiation so long as the intention is curative. Further details can be obtained from Dr F. Senanayake, Departof Radiotherapy & Oncology, Royal Free Hospital, Pond Street, London NW3.
ment
Newcastle General
Westminster Hospital, London
R. WILSON I. W. F. HANHAM
The London
G. MAIR
Hospital
Hospital Royal Victoria Hospital, Folkestone Folkestone Hospital Hammersmith Hospital, London Royal Free and St. Thomas’ Hospitals, London Royal Free Hospital
Royal Free Hospital Royal Free and Royal Northern Hospitals, London
S. R. DRAKE C. D. DERRY C. MCKENZIE B. A. STOLL E. BOESEN D. B. L. SKEGGS F. SENANAYAKE
1. Fisher, B., and others, New Engl. J. Med. 1975, 292, 117 2. Bonadonna, G., and others, Cancer, 1977, 39, suppl. p. 2905. 3. Meakin, J. W., and others, in Adjuvant Therapy of Cancer (edited by S. E. Salmon and S. E. Jones), p. 95. Amsterdam, 1977. 4. Cavalli, F., and others, 4th int. Congr. Chemother. 1977, abstr. 510, 615. 5. Ahmann, D. L., and others, New Engl. J. Med., 297, 356 6. Ward, H. W. C. Br. med. J. 1973, i, 13
