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Al Segaloff: Recollections from England
205
AL SEGALOFF: R E C O L L E C T I O N S FROM ENGLAND R.D. Bulbrook Clinical Endocrinology Laboratories Imperial Cancer Research Fund Lincoln's Inn Fields P.O. Box 12B London WC2A 3PX In common with many others all over the world, I was distressed to hear of A1 Segaloff's death.
In what follows I have not attempted to
make a systematic evaluation of his considerable achievements but have written down what I remember of a long association with him in which he taught me a great deal about clinical and endocrinological
aspects of
breast cancer. A1 first erupted into one's consciousness
in the early 60's when he
visited London with the aim of bringing the fruits of American breast cancer research to the suspicious and backward natives.
We had never
seen his like before. In surroundings that would have intimidated Attila the Hun, he stood up and described in detail the faults in British work.
In particular, he
was outraged that response to treatment was not monitored by external reviewers.
Among his audience were the last of the dinosaur consultant
surgeons, men of immense power and authority, whose minds had never been confused by controlled clinical trials. got better, and that was that. how to run their clinics.
When the gods operated, patients
And there was diminutive A1 telling them
When A1 eventually left (left is too mild a
term - it was more like a stage exit of the Demon King) he left several people in a state of shock.
The concept that a veteran surgeon could be
wrong about the response of his patients was totally abhorrent. A1 escaped with his life to the States but didn't let the matter drop.
March, April 1~8fi
Steroids
V o l u m e 45, N u m b e r s 3,4
206
~
-z- m ~ o
x z~m
John Hayward and I were invited to attend a clinical review at an American hospital. viewers.
A1, Mike Brennan and George Escher were the external re-
A violent argument broke out over the first patient.
While
the reviewers exchanged abuse the case-presenter ignored the uproar and went steadily on with four more cases, ignored by the reviewers.
The
last patient was a woman with a bony metastasis in the skull who had been treated with a new wonder steroid. The third skull film showed a complete remission which was accompanied by the disappearance of the patient's teeth.
Subsequent films showed a return of both the metastasis and teeth.
In other words, the film on which the classification of complete remission was based belonged to somebody else.
We concluded that the princi-
ple of external review was excellent but the practice might be less than perfect. Over the next decade, external review was steadily introduced in England, sometimes with devastating results when a cherished series was decimated because no real clinical evidence existed.
The British Breast
Group helped the transformation to a scientific assessment of response by publishing detailed criteria in 1974.
These were superseded in 1977
by guide-lines from a UICC committee oh which A1 sat. It took a long time but, by sheer force of personality, A1 altered irrevocably the ingrained habits of generations of clinicians.
It was
quite an achievement. Perhaps his major piece of work was the search for new hormonal agents for additive therapy.
During his long tenure as Chairman of the Cooper-
ative Breast Cancer Group, A1 set out with the simple thesis that as stilboestrol and testosterone could bring about remissions in about a
~r ~
~ffio
x ~,~
207
third of the patients, then allied compounds might increase the remission rate and might have fewer side-effects. and the costs must have been astronomical.
The effort was formidable It has to be said that,
while better agents were discovered, no "wonder steroid" emerged.
Indeed,
it is ironic that the nearest approach to such a compound came from an unexpected source when ICI introduced tamoxifen.
Nevertheless, the orig-
inal c o n c e p t w a s right and it took great courage and determination to push the project through. An innovation stemming from the clinical trials of new compounds was the stratification of patients according to the predominant metastatic site and by menopausal status.
The variation of response by site and,
in particular, the poor response of women with recurrence in the first 5 years after menopause was recognised.
This eminently sensible approach
now seems to have been forgotten and it is incomprehensible to me that in some of the new trials on adjuvant endocrine therapy the menopausal effect has been ignored.
Multicenter trials are now commonplace but A l a n d
his colleagues laid the groundwork which made them practicable. A1 introduced another pioneering study during the trials of new compounds by measuring endocrine function.
He hoped that responsive
tients might be characterized by particular hormone patterns.
pa-
The problem
here was that the idea was way ahead of the analytical technology available : for instance, prolactin had to be measured by pigeon crop assays, which were dreadful.
Once again, the concept was sensible but was based
on the widely held assumption that there would be large differences in endocrine function when patients and controls or when responsive and unresponsive patients were compared ; differences which could be picked up using crude assays.
It has taken another 25 years to show that differ-
208
~ ~ o x x ~
ences, where they exist at all, are subtle. I visited East Germany with A1 and George Escher in 1965. he happened to be, A l w o u l d
Wherever
lay down the law about research and treat-
ment of breast cancer in an uncompromising manner. somewhat shaken audiences across the country.
He left a trail of
Any half-reasonable
re-
search worker can trot out his current results, most of which will turn out to be ephemeral.
It takes a special sort of man to insist on the im-
plementation of rigid standards, to deal in principles, without any regard for the place or the audience. (if you will forgive the American turn of phrase).
and to do this
Emollient, he wasfft At a meeting on clin-
ical evaluation in breast cancer held in London in 1965, the records show that Al's first two interjections and "I strongly disagree."
in the discussions were "I disagree"
These look fairly innocuous in print but they
were delivered verbally with a thrust roughly equivalent to that of a Concorde engine and to an audience used to saccharine. his whole body into these interjections
He used to put
in exactly the same way that a
tennis player serves an ace. It should be apparent from these random recollections that I andmany other Europeans had a great respect for Al's achievements. personally miss him greatly because his temperament
But I shall
suited me.
I liked
the combination of torrential abuse about one's research (which, in retrospect, was sometimes Justified) combined with a warm heart when science wasn't involved. again.
He was unique, and we shall not see his like
,
AL SEGALOFF: R E C O L L E C T I O N S FROM ENGLAND R.D. Bulbrook Clinical Endocrinology Laboratories Imperial Cancer Research Fund Lincoln's Inn Fields P.O. Box 12B London WC2A 3PX In common with many others all over the world, I was distressed to hear of A1 Segaloff's death.
In what follows I have not attempted to
make a systematic evaluation of his considerable achievements but have written down what I remember of a long association with him in which he taught me a great deal about clinical and endocrinological
aspects of
breast cancer. A1 first erupted into one's consciousness
in the early 60's when he
visited London with the aim of bringing the fruits of American breast cancer research to the suspicious and backward natives.
We had never
seen his like before. In surroundings that would have intimidated Attila the Hun, he stood up and described in detail the faults in British work.
In particular, he
was outraged that response to treatment was not monitored by external reviewers.
Among his audience were the last of the dinosaur consultant
surgeons, men of immense power and authority, whose minds had never been confused by controlled clinical trials. got better, and that was that. how to run their clinics.
When the gods operated, patients
And there was diminutive A1 telling them
When A1 eventually left (left is too mild a
term - it was more like a stage exit of the Demon King) he left several people in a state of shock.
The concept that a veteran surgeon could be
wrong about the response of his patients was totally abhorrent. A1 escaped with his life to the States but didn't let the matter drop.
March, April 1~8fi
Steroids
V o l u m e 45, N u m b e r s 3,4
206
~
-z- m ~ o
x z~m
John Hayward and I were invited to attend a clinical review at an American hospital. viewers.
A1, Mike Brennan and George Escher were the external re-
A violent argument broke out over the first patient.
While
the reviewers exchanged abuse the case-presenter ignored the uproar and went steadily on with four more cases, ignored by the reviewers.
The
last patient was a woman with a bony metastasis in the skull who had been treated with a new wonder steroid. The third skull film showed a complete remission which was accompanied by the disappearance of the patient's teeth.
Subsequent films showed a return of both the metastasis and teeth.
In other words, the film on which the classification of complete remission was based belonged to somebody else.
We concluded that the princi-
ple of external review was excellent but the practice might be less than perfect. Over the next decade, external review was steadily introduced in England, sometimes with devastating results when a cherished series was decimated because no real clinical evidence existed.
The British Breast
Group helped the transformation to a scientific assessment of response by publishing detailed criteria in 1974.
These were superseded in 1977
by guide-lines from a UICC committee oh which A1 sat. It took a long time but, by sheer force of personality, A1 altered irrevocably the ingrained habits of generations of clinicians.
It was
quite an achievement. Perhaps his major piece of work was the search for new hormonal agents for additive therapy.
During his long tenure as Chairman of the Cooper-
ative Breast Cancer Group, A1 set out with the simple thesis that as stilboestrol and testosterone could bring about remissions in about a
~r ~
~ffio
x ~,~
207
third of the patients, then allied compounds might increase the remission rate and might have fewer side-effects. and the costs must have been astronomical.
The effort was formidable It has to be said that,
while better agents were discovered, no "wonder steroid" emerged.
Indeed,
it is ironic that the nearest approach to such a compound came from an unexpected source when ICI introduced tamoxifen.
Nevertheless, the orig-
inal c o n c e p t w a s right and it took great courage and determination to push the project through. An innovation stemming from the clinical trials of new compounds was the stratification of patients according to the predominant metastatic site and by menopausal status.
The variation of response by site and,
in particular, the poor response of women with recurrence in the first 5 years after menopause was recognised.
This eminently sensible approach
now seems to have been forgotten and it is incomprehensible to me that in some of the new trials on adjuvant endocrine therapy the menopausal effect has been ignored.
Multicenter trials are now commonplace but A l a n d
his colleagues laid the groundwork which made them practicable. A1 introduced another pioneering study during the trials of new compounds by measuring endocrine function.
He hoped that responsive
tients might be characterized by particular hormone patterns.
pa-
The problem
here was that the idea was way ahead of the analytical technology available : for instance, prolactin had to be measured by pigeon crop assays, which were dreadful.
Once again, the concept was sensible but was based
on the widely held assumption that there would be large differences in endocrine function when patients and controls or when responsive and unresponsive patients were compared ; differences which could be picked up using crude assays.
It has taken another 25 years to show that differ-
208
~ ~ o x x ~
ences, where they exist at all, are subtle. I visited East Germany with A1 and George Escher in 1965. he happened to be, A l w o u l d
Wherever
lay down the law about research and treat-
ment of breast cancer in an uncompromising manner. somewhat shaken audiences across the country.
He left a trail of
Any half-reasonable
re-
search worker can trot out his current results, most of which will turn out to be ephemeral.
It takes a special sort of man to insist on the im-
plementation of rigid standards, to deal in principles, without any regard for the place or the audience. (if you will forgive the American turn of phrase).
and to do this
Emollient, he wasfft At a meeting on clin-
ical evaluation in breast cancer held in London in 1965, the records show that Al's first two interjections and "I strongly disagree."
in the discussions were "I disagree"
These look fairly innocuous in print but they
were delivered verbally with a thrust roughly equivalent to that of a Concorde engine and to an audience used to saccharine. his whole body into these interjections
He used to put
in exactly the same way that a
tennis player serves an ace. It should be apparent from these random recollections that I andmany other Europeans had a great respect for Al's achievements. personally miss him greatly because his temperament
But I shall
suited me.
I liked
the combination of torrential abuse about one's research (which, in retrospect, was sometimes Justified) combined with a warm heart when science wasn't involved. again.
He was unique, and we shall not see his like
,