Corticosteroids for Elderly Patients with Breast Cancer

M. J. MINTON, MRCP,* R. K. KNIGHT, FRCP,t R. D. RUBENS, MRCP,* AND J. L. HAYWARD, FRCSg

Ninety-one assessable elderly women ( 3 6 5 years) with advanced breast cancer were treated with
prednisolone 15 mg (or cortisone 75 mg) daily after primary endocrine treatment (estrogens, androgens
or tamoxifen). Thirteen (14%)achieved an objective regression, and 19 (21%)others showed no change
for ssix months. Hence, 32 patients (35%)had control of disease for about one year. Responses were
mainly in soft tissue and skeletal lesions and were independent of response to prior endocrine treatment.
Toxicity was low. Low-dose corticosteroid treatment is of value in controlling advanced breast cancer
in elderly women.
Cancer 48:883-887, 1981.

C ORTICOSTEROIDS have been used in patients with

advanced breast cancer for many years. Dosage
and results have varied widely, and there is still no clear
indication of the optimal therapeutic regimen. Doses
used have varied from between the equivalent of 10 to
100 mg of prednisolone daily, and the response rates
quoted using variable criteria have ranged from 0% to
57% (Table 1). It has been the practice of the physicians
in this Unit, over the last 16 years, to use low-dose
corticosteroids in preference to ablative procedures for
elderly patients ( 3 6 5 years) who had relapsed after
primary additive endocrine therapy.
Materials and Methods
One hundred and eleven women ( 3 6 5 years) with
advanced breast cancer received prednisolone as
definitive treatment. Ninety-one patients were assess-
able for objective response. Prednisolone dosage was
15 mg daily. Ten patients early in the series received
cortisone acetate 75 mg daily instead. Twenty patients
were excluded from assessment because: (1) pred-
nisolone was given with another drug or radiotherapy
(4 patients); (2) disease was not assessable by the
U.I.C.C. riter ria,^'^ e.g., cerebral metastatic disease or
sclerotic bone deposits as sole lesions (4 patients); (3)
~~~
prednisolone was used for control of hypercalcemia
(4patients); (4) prednisolone was given for less than one
month. Six patients who received prednisolone termi-
nally were excluded on this basis; and (5) incomplete
follow-up examinations (2 patients).
The patients studied had progressive disease follow-
ing treatment with estrogens, tamoxifen, or androgens.
In many cases, a period of one month or longer with no
treatment (the withdrawal period) was undertaken be-
fore commencing prednisolone treatment to exclude a
withdrawal response to the primary hormone treat-
ment. However, some patients had no withdrawal
period and these are noted. The characteristics of the
91 assessable patients are given in Table 2.
Palpable and visible lesions were measured by their
maximal perpendicular diameters and photographs
taken of the cutaneous lesions. Radiographs of chest,
skull, total spine, pelvis, and femora were also ob-
tained. Radioisotope scans of the liver were performed
when clinically indicated. Strict criteria of response
were used as defined by the U.I.C.C.7xR
Complete response
Disappearance of all known disease. In the case of
lytic bone metastases, these must be shown radio-
logically to have recalcified.

From the Imperial Cancer Research Fund (I.C.R.F.), Breast

Cancer Unit, Guy’s Hospital, London, England.
* Research Fellow.
t Consultant Physician, Guy’s Hospital.
t Deputy Director, I.C.R.F. Breast Unit.
(i Director, I.C.R.F. Breast Unit.
Address for reprints: R. D. Rubens, Breast Unit, Guy’s Hospital,
London, S EI , 9RT England.
The authors thank Miss Sheila Sexton for the statistical analyses
and Miss Lynda Fletcher for typing the manuscript.
Accepted for publication July 23, 1980.
Partial response
Greater than a 50% decrease in the product of per-
pendicular diameters of measurable lesions and objec-
tive improvement in other assessable lesions, these
observations to be confirmed on two successive oc-
casions at least one month apart. No new lesions must
appear.

0008-543X/81/0815/883/$0.80 0 American Cancer Society

883
884 CANCERAugust 15 1981 Vol. 48

TARLE
1. Published Data on the Response of Advanced Breast Cancer to Corticosteroid Therapy

Author and Corticosteroid Response Mean duration

reference No. patients daily dose rate of response Criteria of response

Pearson et Group a: not stated Cortisone 3 months Criteria not specified;

Group b: 14 a. 200-300 mg a. 30-50F symptomatic improvement
b. 50-75 mg b. 14% f objective response

Kofman el ( I / . ~ : ~ 45 Prednisolone 18% Range 3- 12 months Nathanson’s

50- 100 mg
Lemon” 31 Prednisolone 30 mg 48% 9.7 months Included subjective assessment
+ ovarian ablation if and biochemical changes
<65 years
y . ..
I issen-Meyer
37 Cortisone 50 mg 5 1% 12 months Includes subjective assessment
and Vogt” + ovarian ablation and no change for 6 of 12
(13 patients were patients
premenopausal)
Dao et (11.:’ 19 Cortisone SO mg 0% - Objective criteria of response
Gardner r t ~ 1 . ~ 46 Prednisolone 30 mg 24% 6 months (range Cooperative Breast Cancer
+ liothyronine S O Fg 1-15 months) Group‘%
Van Gilse”’ 109 Cortisone 100 mg until 37.6% 6 months Nathanson’s objective criteria
1956; prednisolone + subjective assessment and
20 mg biochemical changes
Stoll’4 80 Prednisolone 30 mg 11% 3 months Nathanson’s criteria
Moore et al. I H 79 Not specified 57% 6 months Subjective and objective criteria
Bet hune’ 73 Cortisone 37.5-50 mg 43% 12 months (range Combination of subjective and
3-30) in 6 patients objective improvement
34 Treatment started with 3070 Not stated Objective criteria >50%
cortisone 300 mg or shrinkage of tumor
prednisolone 200 mg
then reduced to
60-90 mg
Forrest et 53 Prednisoione 30 mg (26 25% 16 months Criteria not ytated but all had
patients) dex- objective remissions
amethasone 4.5 mg
(27 patients)

No chting~ duration of response in this group was 15 months. In

Lesions unchanged (i.e., less than 50% decrease or
less than 25% increase in the size of measurable
lesions).
Psog sc s s iv c disc I I s ti
Progression of some or all lesions and/or appearance
of new lesions. N o lesions regress.
Llir sri t ion o f scsponse
In a patient who has an objective regression, this
is to be dated from the start of therapy until either new
lesions appear or any one existing lesion increases by
2S% or more above its smallest size recorded.
Results
Objective responses to corticosteroids were seen in
13 (14%) of the 91 women studied (Table 3). The median
six of these patients, there was no interval between
ending primary endocrine treatment and starting corti-
costeroids, so a hormonal withdrawal response to es-
trogens (four patients) or androgens (two patients)
cannot be excluded. However, this is not likely to have
appreciably altered the overall response rate to cortico-
steroids as the withdrawal response is uncommon, and
is most likely to occur in patients who have responded
to the prior endocrine therapy.“;2:‘ Only two of the six
patients had responded to primary endocrine therapy.
There was n o withdrawal period in 6 of 19 patients in
the no-change group and 20 of 59 patients with pro-
gressive disease. Nineteen women (21%) who were
classified as “no change” for a minimum of six months
had a median response duration of nine months
(Table 3 ) .
The extent of different sites involved was com-
parable in each of the response categories. The
majority of patients (59%) had one metastatic site of
No. 4 CORTICOSTEROIDS
FOR ELDERLY
PATIENTS
WITH BREAST
CANCER . Minton et al. 885

disease involved, 39% had two sites, and 5% had three TABLE2. Characteristics of Patients* Age:
Median 69 yrs (Range 65-88)
sites. The response of the tumor to treatment was
predominantly in soft tissue lesions, but four patients No. patients
with lytic bone disease showed evidence of sclerosis ~

Menopausal status at diagnosis

(Table 4). Postmenopausal ( > 5 - ~ 1 0 years) 12
In 83 of the patients, the response to prior endocrine Postmenopausal (> 10 years) 79
therapy was assessable. Thirty patients (36%) had com- Disease-free interval
0 months 43
plete or partial responses, but only three of these re- 0-24 months 13
sponders (10%) subsequently responded to pred- >24 months 35
nisolone. In the other 53 patients who had not re- Stage at first diagnosis
Operable (1, 11) 47
sponded to primary endocrine treatment , eight patients Primarily advanced (111, IV) 44
(15%) responded to prednisolone. Previous treatment for advanced
Corticosteroids were well tolerated by the majority diseaset
Estrogens 64
of patients. Two patients bled from gastric ulcers after Tamoxifen 15
eight months of therapy. In one, there was no further Androgens 14
bleeding after the dose of prednisolone was reduced Time from diagnosis to start of
treatment with prednisolone
to 10 mg daily, while the other patient died of pneu- 0-23 months 31
monia two months later. In two other patients, acute 24-60 months 40
bleeding from a gastric ulcer and a gastric perfora- >60 months 20
tion, respectively, were terminal complications. Four * Patient age: 65-88; median, 69 years.
patients experienced significant weight gain (>6 kg) t Two patients had both estrogen and androgen therapies prior
and Cushing’s facies, which occurred after two to six to prednisolone.
months of therapy, and was controlled by reducing the
dose of prednisolone to 10 mg daily. One of the four costeroids and previous endocrine therapy was
patients remained on treatment for 16 months and re- Seen *6,24,27
quired no further dose reduction. Two patients devel- Our response rate is lower than that reported for
oped diabetes mellitus while on steroids, which was surgical a d r e n a l e c t ~ m yor~ ~inhibition
~~ of adrenal ac-
controlled by diet and oral hypoglycemic agents. tivity with aminoglutethimide, although the latter has
Survival in patients showing partial response or no not been compared directly with c o r t i c o ~ t e r o i d s . ~ ’ ~ ~ ~
change in their disease was significantly better ( P Dao et ~ 1 observed
. ~ no response to treatment in 19
< 0.01) than those patients showing no response to patients treated with cortisone 50 mg daily when this
corticosteroids (Fig. 1 and Table 3), using the log- was compared to adrenalectomy which caused re-
rank test. l 9 gressions in 8 of 18 patients. This lack of response may
be explained by the lower dose of corticosteroids and
Discussion differences in patient characteristics, which included
a younger age group of women and 12 of 19 (63%)
Previously reported response rates of patients on
corticosteroids vary from 0-57% (Table 1). These re-
sults have been obtained using different criteria of TABLE3. Response to Rednisolone
response, sometimes combining corticosteroids with
Duration of response
other treatments, and some authors have included sub- (months)
jective responses and control of hypercalcemia. St0l1’~ No.
has reported a series of 80 patients on 30 mg pred- patients Mean Median Range
nisolone daily using Nathanson’s criteria of response Objective regression
with a 25% reduction in lesion diameters as evidence Complete response 0 - - -
of objective r e r n i s s i ~ nHis
. ~ ~series
~ ~ ~included both pre- Partial response 13 25 15 (5-50)
No change ( 3 6 months) 19 13 9 (6-44)
menopausal and postmenopausal women with an 11% Progressive disease 59 - - -
response rate. Stoll commented that doses lower than TOTAL 91
30-mg prednisolone daily seemed to be of less value.
Our results using strict criteria of response show that Median survival time from start of prednisolone
15 mg prednisolone daily achieves similar results in Months Range
postmenopausal women to those found by Stoll, and at
this dosage, the drug was well tolerated for long Partial responders 27 (6-55)
No change 3 6 months 22 (8-80)
periods of time. Similar to other authors’ experiences, Progressive disease 9 (2-57)
no predictive correlation between a response to corti-
886 CANCERA ugust 15 1981 Vol. 48

‘TABLE 4. Response at Different Sites
Site
~~~
Breast
Lymphatic
Cutaneous
Skeletal
Pulmonary
Hepatic
* Denominators indicate the number of patients with involvement
of the stated site at the start of treatment with prednisolone and
numerators show the number with a regression at that site.
dying within six months of starting treatment (Tables
2 and 3).
The precise mechanism of action of corticosteroids
on breast tumors is not known, but is probably through
several pathways. Inhibition of adrenocortical function
is one possibility, but while prednisolone produces
some adrenal suppression, there is a variable degree of
adrenal atrophy,“’ and unlike aminoglutethimide, it
has no inhibitory effect on estrogen synthesis in
extraglandular tissues.“
The demonstration of specific cytosol hormone re-
ceptors for glucocorticoids in breast tumors28and their
association with the presence of estrogen receptors
in human breast cancer,’ illustrate another possible
mode of action.ls A recent studyz0 reported a strong
correlation between response and estrogen receptor-
positive tumors. In this series, 15 of 32 estrogen re-
ceptor-positive tumors responded to 10 mg pred-
nisolone daily, while there were no responders in the
group of 19 estrogen receptor-negative tumors. These
results show a high response rate and have not as yet
been confirmed by other workers; moreover, pred-
nisolone was used in combination with an androgen,
thus confusing the interpretation.
ioo
In our series, estrogen receptor information was
Regressions* available in only a few patients. Of 14 patients with
estrogen receptor-positive tumors, 12 were assessable
8/41 (20%) for response to prior treatment with estrogens, andro-
5/61 (8%)
7/50 (14%)
gens, or tamoxifen and four of these patients (33%)
4/40 (10%) achieved partial responses. Only one of the 14 patients
1/16 (6%) responded subsequently to prednisolone. In this small
117 (14%)
group of patients, there would seem to be no positive
correlation between estrogen receptors and response to
prednisolone.
The patients in our study were elderly (median age:
69 years) with a predominance of soft tissue and skele-
tal disease that would be expected to respond favorably
to endocrine treatment. This was confirmed by a 36%
response rate to primary endocrine treatment. The 14%
response rate to subsequent prednisolone administra-
tion is low, but effective palliation was administered
for about a year to 35% of patients (partial responders
+ no change) in whom ablative surgery and chemo-
therapy would probably not have been appropriate. In
the group of patients within the “no change” category
for six months or more, 11 of 19 patients had bone
disease as the major site of metastatic disease and this
probably reflects the difficulty in obtaining objective
evidence of response at this site. Recalcification in
the skeleton was rare and only seen after many months
of treatment.’*
While it has long been recognized that prednisolone
can produce subjective improvement in patients with
breast cancer and occasionally short-term palliation
for visceral metastases, there is no consensus as to
when this treatment should be selected in treating
advanced breast cancer. Our experience demonstrates
that low-dose prednisolone can achieve effective
palliation for approximately one year in one third of
elderly patients with soft tissue and skeletal metastatic
disease,without severe toxicity, after failure of primary
endocrine treatment.

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Familial Ovarian Cancer Registry

There are increasing reports of ovarian cancer occurring in two or more family members. The
Familial Ovarian Cancer Registry will evaluate this increase to obtain information for genetic counsel-
ing to family members. Case accrual will evaluate:
1. the number of cases of familial ovarian cancer
2. the type of inheritance
3. the relationship to breast and endometrial carcinoma
4. the study of environmental, geographical and racial factors
5. genetic counseling.
Please send information regarding the clinical history of any family with two or more members
with ovarian cancer to:
Familial Ovarian Cancer Registry
M. Steven Piver, MD
Roswell Park Memorial Institute
New York State Department of Health
666 Elm Street
Buffalo, NY 14263 (716) 845-3110