183
Clinica Chimica A&a, 67 (1976) 183-187 0 Elsevier Scientific Publishing Company,
Amsterdam
- Printed
in The Netherlands
CGA 7570
CORTICOSTEROID SULFATE EXCRETION RECE~ORS IN BREAST CANCER
DAVID
P. ROSE and LINA LISKOWSKI
Division
of Clinical Oncology,
~a~ison,
(Received
Wise. 53706
(U.S.A.)
September
22, 1975)
University
Hospitals,
AND ESTROGEN
I300
University
Avenue,
Summary The urinary excretion of corticosteroid sulfates and free cortisol were determined in 150 breast cancer patients, Four of 60 cases of early breast cancer (7%) and 26 of 90 patients with advanced breast cancer (29%) showed an elevated urinary corticosteroid sulfate excretion. Urinary free cortisol was usually normal. Estrogen receptor assays were performed on tumor samples from 67 breast cancer patients; .24 were from primary lesions obtained at mastectomy, 3 from inoperable primaries in patients with systemic metastases, and 40 from metastases. Sixteen of the primary breast cancers (67%), 26 of the metastases (65%) and 1 of the 3 inoperable primaries contained estrogen receptors. With 2 exceptions, patients with an increased urinary corticosteroid sulfate excretion also had estrogen receptor-cont~ning tumors.
Introduction Between 20 and 30% of women with recurrent breast cancer benefit from endocrine ablative surgery, or some other form of hormone therapy. A number of biochemical tests have been proposed in an attempt to predict those patients who will show a favorable response to hormonal manipulation. Dao and Libby [l] reported that patients who fail to respond to adrenalectomy have tumors which show high e&radio1 sulfurylating activity relative to the sulfation of dehydroepi~drosterone. Conversely, they found that patients whose tumor contained relatively higher dehydroepiandrosterone sulfurylating activity are usually responsive to endocrine ablation. The observation by Ghosh et al. [2] that some breast cancer patients excrete increased quantities of urinary corticosteroid sulfates led to the suggestion that their measurement might provide an indirect reflection of tumor sulfurylase activity.
184
Estrogen receptors (ER) are demonstrable in approximately 70% of human breast cancers [3,4]. Their absence indicates that a patient has less than a 10% chance of responding to endocrine therapy; their presence is associated with a remission of advanced breast cancer in about 55% of cases (5 J . The objectives of the present study were to extend our observations on urinary corticosteroid sulfate (UCS) excretion in various stages of breast cancer, and to determine whether an elevated UCS level occurs more frequently in patients with ER-containing breast cancers than in those lacking receptor. The latter would be expected if these two characteristics are both predictors of hormone responsiveness. Urinary free cortisol (UFC) excretion was also determined, in order to provide an indication of cortisol production rate. Materials and methods A total of 150 breast cancer patients were included in the investigation of UCS excretion. Some of the earlier results were included in a preliminary report [6] . There were 60 cases of early breast cancer, 33 with local recurrences or pleural effusions without evidence of underlying pulmonary involvement, and 57 with systemic metastases. The controls were 31 healthy women, aged 30-75 years, none of whom was taking any form of steroid preparation. Breast cancer tissue for the correlation of ER levels with UCS excretion was available from 67 patients; 24 samples were obtained from a primary tumor at the time of mastectomy, 3 were from inoperable primary lesions in patients with systemic metastases, and 40 from metastases. The tissue diagnosis was confirmed by histological examination, The biopsy sites for metastatic tumor estrogen receptor assays were lymph node (21 cases), skin (15), bone (2), ovary (1) and lung (1). Twenty-one of the 40 advanced breast cancer cases had locally recurrent disease and 19 had systemic metastases. Corticosteroid sulfates [7], which represent the sum of cortisol, cortisone, corticosterone and lldehydrocorticosterone sulfates, and the UFC [8] were determined in 24-h urine collections by competitive protein-binding techniques. The urinary sulfate conjugates were hydrolyzed according to the method of Burstein and Lieberman [9] ; a petroleum ether step was included in the extraction procedure [7]. Statistical comparison between groups was by Students t-test; values for p of
Clinica Chimica A&a, 67 (1976) 183-187 0 Elsevier Scientific Publishing Company,
Amsterdam
- Printed
in The Netherlands
CGA 7570
CORTICOSTEROID SULFATE EXCRETION RECE~ORS IN BREAST CANCER
DAVID
P. ROSE and LINA LISKOWSKI
Division
of Clinical Oncology,
~a~ison,
(Received
Wise. 53706
(U.S.A.)
September
22, 1975)
University
Hospitals,
AND ESTROGEN
I300
University
Avenue,
Summary The urinary excretion of corticosteroid sulfates and free cortisol were determined in 150 breast cancer patients, Four of 60 cases of early breast cancer (7%) and 26 of 90 patients with advanced breast cancer (29%) showed an elevated urinary corticosteroid sulfate excretion. Urinary free cortisol was usually normal. Estrogen receptor assays were performed on tumor samples from 67 breast cancer patients; .24 were from primary lesions obtained at mastectomy, 3 from inoperable primaries in patients with systemic metastases, and 40 from metastases. Sixteen of the primary breast cancers (67%), 26 of the metastases (65%) and 1 of the 3 inoperable primaries contained estrogen receptors. With 2 exceptions, patients with an increased urinary corticosteroid sulfate excretion also had estrogen receptor-cont~ning tumors.
Introduction Between 20 and 30% of women with recurrent breast cancer benefit from endocrine ablative surgery, or some other form of hormone therapy. A number of biochemical tests have been proposed in an attempt to predict those patients who will show a favorable response to hormonal manipulation. Dao and Libby [l] reported that patients who fail to respond to adrenalectomy have tumors which show high e&radio1 sulfurylating activity relative to the sulfation of dehydroepi~drosterone. Conversely, they found that patients whose tumor contained relatively higher dehydroepiandrosterone sulfurylating activity are usually responsive to endocrine ablation. The observation by Ghosh et al. [2] that some breast cancer patients excrete increased quantities of urinary corticosteroid sulfates led to the suggestion that their measurement might provide an indirect reflection of tumor sulfurylase activity.
184
Estrogen receptors (ER) are demonstrable in approximately 70% of human breast cancers [3,4]. Their absence indicates that a patient has less than a 10% chance of responding to endocrine therapy; their presence is associated with a remission of advanced breast cancer in about 55% of cases (5 J . The objectives of the present study were to extend our observations on urinary corticosteroid sulfate (UCS) excretion in various stages of breast cancer, and to determine whether an elevated UCS level occurs more frequently in patients with ER-containing breast cancers than in those lacking receptor. The latter would be expected if these two characteristics are both predictors of hormone responsiveness. Urinary free cortisol (UFC) excretion was also determined, in order to provide an indication of cortisol production rate. Materials and methods A total of 150 breast cancer patients were included in the investigation of UCS excretion. Some of the earlier results were included in a preliminary report [6] . There were 60 cases of early breast cancer, 33 with local recurrences or pleural effusions without evidence of underlying pulmonary involvement, and 57 with systemic metastases. The controls were 31 healthy women, aged 30-75 years, none of whom was taking any form of steroid preparation. Breast cancer tissue for the correlation of ER levels with UCS excretion was available from 67 patients; 24 samples were obtained from a primary tumor at the time of mastectomy, 3 were from inoperable primary lesions in patients with systemic metastases, and 40 from metastases. The tissue diagnosis was confirmed by histological examination, The biopsy sites for metastatic tumor estrogen receptor assays were lymph node (21 cases), skin (15), bone (2), ovary (1) and lung (1). Twenty-one of the 40 advanced breast cancer cases had locally recurrent disease and 19 had systemic metastases. Corticosteroid sulfates [7], which represent the sum of cortisol, cortisone, corticosterone and lldehydrocorticosterone sulfates, and the UFC [8] were determined in 24-h urine collections by competitive protein-binding techniques. The urinary sulfate conjugates were hydrolyzed according to the method of Burstein and Lieberman [9] ; a petroleum ether step was included in the extraction procedure [7]. Statistical comparison between groups was by Students t-test; values for p of
