- Email: [email protected]
ADJUVANT TAMOXIFEN THERAPY AND RECEPTOR LEVELS
573 scores, and seven had deteriorated. These differences may arise either from a beneficial effect of regular supplementary hyperbaric oxygen treatment in preventing deterioration or from self-selection of therapy in that deteriorating patients were likely to stop treatment. There is therefore still a possibility that regular hyperbaric oxygen treatment every 1-3 weeks may be beneficial. There is a need for a large controlled trial to examine this question now, for many patients are receiving or considering hyperbaric oxygen treatment without adequate evidence for its long-term value.
TABLE II-COMPARISON OF THE PATIENTS ENTERED INTO TWO TRIALS OF
ADJUVANT TAMOXIFEN THERAPY
Department of Medicine, Ninewells Hospital and Medical School, Dundee DDI 9SY
D. L. W. DAVIDSON
SIR,-Dr Barnes and colleagues’ study refutes claims made for hyperbaric oxygen in multiple sclerosis. Nevertheless a subjective improvement in bladder function was noted. The patients could detect no difference between simulated and genuine compression; however, patients in the oxygen group showed some complications of therapy (notably barotrauma). Thus the treatment should not be considered to have been completely blind, and the subjective improvement may have been related to this. 57
Upper Tooting Park,
G.S. PLAUT
London SW17 7SU
ADJUVANT TAMOXIFEN THERAPY AND RECEPTOR LEVELS
SIR,-In view of the clinical importance of the results of the Danish Breast Cancer Cooperative Group’s trial (Jan 5, p 16) we have done a crude analysis of the current results of our Scottish trial of adjuvant tamoxifen and have related these results to tumour oestrogen receptor (ER) status. This trial compares, in women with primary breast cancer initially treated by either mastectomy and node sampling (followed by postoperative radiotherapy when nodes were affected) or mastectomy and axillary clearance, adjuvant tamoxifen therapy (20 mg per day for five years) versus no immediate systemic therapy, tamoxifen being given at the first evidence of recurrence. Of 1323 randomised patients, 666 have had ER levels estimated. In table I we compare the proportion of 230 postmenopausal node-positive patients who were alive and free from recurrence at a median time of between three and four years with that in the Danish trial. Our results are based on the annual returns of review received to date in the trial office, all patients having been followed for at least one year. The disease-free percentages given for the Danish patients are the three-year levels read from their published graphs, the numbers (which may be inaccurate) having been estimated from the totals given. For the 230 Scottish postmenopausal patients who were node positive there is a consistent trend in favour of those given adjuvant tamoxifen within each of the three ranges of ER concentration. As in the Danish study, this trend becomes significant only for patients with ER levels of 100 fmol/mg protein or more. In the remaining 436 Scottish patients with disease of probable good prognosis the
results follow a similar pattern. The most notable difference between the two studies is the absence in the Scottish trial of the reversal of the effect of treatment found by the Danish group for those with ER levels between 10 and 99 fmols/mg protein. The Danish group did not claim this difference to be significant, and we believe that this is a chance finding due to the small numbers and short follow-up. There may still be some treatment benefit of tamoxifen at low or moderate levels of ER and neither group can claim to have a definitive- answer. We think that the increased incidence of relapse in those patients with ER levels over 100 fmol/mg protein, present in both of the untreated control groups, is of interest. We have reported a similar finding in the and believe it suggests that the relation between ER level and diseasefree survival is more complicated than is generally supposed. While similar in many respects, the Danish and Scottish patients reported in table i are small subgroups selected from larger randomised totals (table 11). Besides differing in initial and adjuvant therapy, the two groups differ in the distribution of their ER values. This may be because the Danish study’s definition of postmenopausal state increased the average age of the patients studied. The apparently greater treatment benefit in the Scottish trial may be explained by the longer duration of therapy. This crude analysis of our data seems to support the conclusions of the Danish group that adjuvant tamoxifen therapy is most likely to be of benefit in patients with tumours rich in oestrogen receptor. This trend accords with most other reported studies, but not with the report of the Nolvadex Adjuvant Treatment Organisation trial which showed no influence of ER status on the results of adjuvant tamoxifen therapy. Receptor analyses in our study were done in just three well-controlled laboratories, 97% being done in Glasgow (Dr R. E. Leake) or Edinburgh (Dr R. A. Hawkins). We understand that this degree of uniformity also applies to the Danish receptor assays.
pastl
The other members of the Scottish Breast Cancer Trials Steering Committee are: Prof A. P. M. Forrest (chairman), Mr A. K. Ah-See, Dr K. Bartlett, Mr U. Chetty, Prof W. Duncan, Prof W. D. George, Dr T. Habeshaw, Dr A. W. Hutcheon, Dr S. B. Kaye, Mr C S. McArdle, Dr M. McCallum, Mr P. Preece, Mrs S. M. Robinson, Dr A. Rodger, Dr J. S. Scott, Mr D. C. Smith and Prof J. F. Smyth. Scottish Cancer Trials Office
(MRC),
HELEN J. STEWART
Medical
ROBIN PRESCOTT,
Teviot Place,
On behalf of the Scottish Breast Cancer Trials Steering Committee
School, University of Edinburgh,
Edinburgh EH8 9AG TABLE I-COMPARISON OF THE RESULTS QF TWO TRIALS OF
ADJUVANT TAMOXIFEN THERAPY’ POSTMENOPAUSAL WOMEN
WITH
BREAST CANCER OF PROBABLE BAD PROGNOSIS ONLY* I
1. Black RB, Prescott
RJ, Bers K, Hawkins RA, Stewart HJ, Forrest APM. Tumor cellularity, estrogen receptors and prognosis in breast cancer. Clin Oncol 1983; 9: 311-18
I
PENTAZOCINE HAMPERS BILE FLOW
’
’Bad prognosis"
as
defined in Danish study paper and as node positivity in Scottish trial.
SIR,-Biliary and pancreatic diseases, especially acute and chronic pancreatitis, are likely to cause severe pain and require potent analgesics. While first-line analgesics do not provide sufficient pain relief in most such patients, opioids should be avoided since they induce spasm of the sphincter of Oddi, thus hampering the flow of bile and pancreatic juice through the papilla of Vater. Thus in these patients newer potent analgesics are often used. However,
TABLE II-COMPARISON OF THE PATIENTS ENTERED INTO TWO TRIALS OF
ADJUVANT TAMOXIFEN THERAPY
Department of Medicine, Ninewells Hospital and Medical School, Dundee DDI 9SY
D. L. W. DAVIDSON
SIR,-Dr Barnes and colleagues’ study refutes claims made for hyperbaric oxygen in multiple sclerosis. Nevertheless a subjective improvement in bladder function was noted. The patients could detect no difference between simulated and genuine compression; however, patients in the oxygen group showed some complications of therapy (notably barotrauma). Thus the treatment should not be considered to have been completely blind, and the subjective improvement may have been related to this. 57
Upper Tooting Park,
G.S. PLAUT
London SW17 7SU
ADJUVANT TAMOXIFEN THERAPY AND RECEPTOR LEVELS
SIR,-In view of the clinical importance of the results of the Danish Breast Cancer Cooperative Group’s trial (Jan 5, p 16) we have done a crude analysis of the current results of our Scottish trial of adjuvant tamoxifen and have related these results to tumour oestrogen receptor (ER) status. This trial compares, in women with primary breast cancer initially treated by either mastectomy and node sampling (followed by postoperative radiotherapy when nodes were affected) or mastectomy and axillary clearance, adjuvant tamoxifen therapy (20 mg per day for five years) versus no immediate systemic therapy, tamoxifen being given at the first evidence of recurrence. Of 1323 randomised patients, 666 have had ER levels estimated. In table I we compare the proportion of 230 postmenopausal node-positive patients who were alive and free from recurrence at a median time of between three and four years with that in the Danish trial. Our results are based on the annual returns of review received to date in the trial office, all patients having been followed for at least one year. The disease-free percentages given for the Danish patients are the three-year levels read from their published graphs, the numbers (which may be inaccurate) having been estimated from the totals given. For the 230 Scottish postmenopausal patients who were node positive there is a consistent trend in favour of those given adjuvant tamoxifen within each of the three ranges of ER concentration. As in the Danish study, this trend becomes significant only for patients with ER levels of 100 fmol/mg protein or more. In the remaining 436 Scottish patients with disease of probable good prognosis the
results follow a similar pattern. The most notable difference between the two studies is the absence in the Scottish trial of the reversal of the effect of treatment found by the Danish group for those with ER levels between 10 and 99 fmols/mg protein. The Danish group did not claim this difference to be significant, and we believe that this is a chance finding due to the small numbers and short follow-up. There may still be some treatment benefit of tamoxifen at low or moderate levels of ER and neither group can claim to have a definitive- answer. We think that the increased incidence of relapse in those patients with ER levels over 100 fmol/mg protein, present in both of the untreated control groups, is of interest. We have reported a similar finding in the and believe it suggests that the relation between ER level and diseasefree survival is more complicated than is generally supposed. While similar in many respects, the Danish and Scottish patients reported in table i are small subgroups selected from larger randomised totals (table 11). Besides differing in initial and adjuvant therapy, the two groups differ in the distribution of their ER values. This may be because the Danish study’s definition of postmenopausal state increased the average age of the patients studied. The apparently greater treatment benefit in the Scottish trial may be explained by the longer duration of therapy. This crude analysis of our data seems to support the conclusions of the Danish group that adjuvant tamoxifen therapy is most likely to be of benefit in patients with tumours rich in oestrogen receptor. This trend accords with most other reported studies, but not with the report of the Nolvadex Adjuvant Treatment Organisation trial which showed no influence of ER status on the results of adjuvant tamoxifen therapy. Receptor analyses in our study were done in just three well-controlled laboratories, 97% being done in Glasgow (Dr R. E. Leake) or Edinburgh (Dr R. A. Hawkins). We understand that this degree of uniformity also applies to the Danish receptor assays.
pastl
The other members of the Scottish Breast Cancer Trials Steering Committee are: Prof A. P. M. Forrest (chairman), Mr A. K. Ah-See, Dr K. Bartlett, Mr U. Chetty, Prof W. Duncan, Prof W. D. George, Dr T. Habeshaw, Dr A. W. Hutcheon, Dr S. B. Kaye, Mr C S. McArdle, Dr M. McCallum, Mr P. Preece, Mrs S. M. Robinson, Dr A. Rodger, Dr J. S. Scott, Mr D. C. Smith and Prof J. F. Smyth. Scottish Cancer Trials Office
(MRC),
HELEN J. STEWART
Medical
ROBIN PRESCOTT,
Teviot Place,
On behalf of the Scottish Breast Cancer Trials Steering Committee
School, University of Edinburgh,
Edinburgh EH8 9AG TABLE I-COMPARISON OF THE RESULTS QF TWO TRIALS OF
ADJUVANT TAMOXIFEN THERAPY’ POSTMENOPAUSAL WOMEN
WITH
BREAST CANCER OF PROBABLE BAD PROGNOSIS ONLY* I
1. Black RB, Prescott
RJ, Bers K, Hawkins RA, Stewart HJ, Forrest APM. Tumor cellularity, estrogen receptors and prognosis in breast cancer. Clin Oncol 1983; 9: 311-18
I
PENTAZOCINE HAMPERS BILE FLOW
’
’Bad prognosis"
as
defined in Danish study paper and as node positivity in Scottish trial.
SIR,-Biliary and pancreatic diseases, especially acute and chronic pancreatitis, are likely to cause severe pain and require potent analgesics. While first-line analgesics do not provide sufficient pain relief in most such patients, opioids should be avoided since they induce spasm of the sphincter of Oddi, thus hampering the flow of bile and pancreatic juice through the papilla of Vater. Thus in these patients newer potent analgesics are often used. However,