lnt. J. Radiation Oncology Biol. Phys. Vol. 4, pp. 469472 @ Pergamon Press Inc., 1978. Printed in the U.S.A.
??Cukrent Concetds in Cancer NEW ROLE OF ENDOCRINE THERAPY IN BREAST CANCERt B. J. KENNEDY,
M.D.
Section of Medical Oncology, Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, U.S.A. Estrogen receptors, Hypophysectomy, Estrogens, Androgens, Breast cancer, Corticosteroids.
estrogen receptor assay results requires cognizance of the techniques of collecting tissue and performance of the test. Specific estrogen receptors (ER) are detectable in 50-80% of breast cancers.” The incidence is considerably lower in premenopausal women (29%) than in postmenopausal women (61%).* The low incidence of ER positivity in premenopausal tumors has been attributed to the presence of high endogenous estrogens which occupy the receptor sites. Correlations have been established between the presence of estrogen receptors and the clinical response to hormonal therapy. Of the patients whose tumors contain estrogen receptors, about two thirds respond to hormonal manipulations. This is approximately double the response rate obtained in clinical studies where patients were treated without regard to estrogen receptor data. Of patients whose tumors lack significant estrogen binding activity, the response rate has been less than 5%. Thus, knowledge of estrogen receptor status provides a means to select the indicated hormonal therapy or chemotherapy specifically for an individual patient. Since it is difficult to obtain tissue for analysis of lesions metastatic to the lungs, liver or bones, it would be advantageous to establish the estrogen receptor values of all breast cancers at the time of the initial biopsy or mastectomy. This information would be an invaluable guide to selecting hormonal therapy at the time of recurrence.5 More recent, quantification of progesterone receptors4 or intranuclear estrogen receptors may be of further value in identifying the biologic nature of hormone-responsive tumors.
The growth of specific breast cancers depends upon hormonal factors. This dependence has been demonstrated by the stimulation of growth by small doses of estrogenic hormone and regression of tumor‘ upon withdrawal of estrogens by oophorectomy, or with administration of large doses of estrogenic hormones. The many hormonal factors involved in breast cancer growth are reflected in the therapeutic regulatory concepts of ablative or administered hormonal therapies. Clinical investigations have developed patterns for successive use of the hormonal therapies, primarily depending on the observed responses to each therapy. About 40% of women with recurrent or metastatic breast cancer will benefit from hormonal therapies. The introduction of chemical therapies, especially combination chemotherapies with regression rates exceeding 65%, distracted physicians from employing hormonal therapies. With the realization that despite these high rates the cancer was not being cured, the hormonal therapies have gained attention again. This has been augmented by the effectiveness of the antiestrogenic agents and the role of estrogen receptor proteins (estrophilin) in designating those breast cancers most likely to respond to hormonal manipulations. The estrogen receptor assay results now provide an improved means for individualizing the selection of hormonal or chemical therapies of breast cancer. Estrogen receptors A Guide to Breast Cancer Therapy. Hormone dependence of breast cancer may be predicted by the results of estrogen receptor measurements. The hormone responsive tumors have a cytoplasmic receptor that binds steroid hormone in vitro. Measurements can be made by using labeled estrogens and a specific inhibitor. Interpretation of
ABLATIVE
HORMONAL
THERAPIES
Bilateral salpingo-ovariectomy is the initial treatment of choice for premenopausal patients with metastatic breast carcinoma. Approximately 40% of
tSupported by Research Grants CA-08832, CA-19527 and CB-64000 from the National Cancer Institute, the Min-
nesota Medical Foundation and the Masonic Memorial Hospital Fund, Inc. 469
470
Radiation
Oncology
0 Biology
0 Physics
patients who are unselected on the basis of estrogen receptor measurements, obtain objective remission of disease. The median period of remission is 9-12 months. Patients who do not respond to ovariectomy, or those who do not have estrogen receptors in their tumors, are treated with combined cytotoxic chemotherapy. Castration is not recommended as an adjuvant therapy at the time of mastectomy.’ Hypophysectomy or bilateral adrenalectomy are employed as secondary endocrine therapies. These ablative procedures will induce objective remissions in 70-90% of premenopausal women who respond to castration or in postmenopausal patients who respond to estrogenic or androgenic hormone administration. The median duration of remission has been 12-14 months. If patients are selected who responded to the initial endocrine (castration or therapy estrogenslandrogens) and who have estrogen receptors present in the metastatic tumor, the response rates to hypophysectomy or adrenalectomy may be even higher.
Estrogens In women who are 4 or more years postmenopausal, the administration of estrogenic hormones in pharmacological doses is the primary endocrine therapy for metastatic breast cancer. The objective remission rate is about 35%, with remissions lasting from several months to many years. In a rare patient cure is regarded as having occurred. The site of the metastatic lesions is of paramount importance. For inoperable primary lesions without dissemination beyond the regional nodes, 55% of objective regressions have been reported.” The response rate is less with pulmonary metastases (40%) or osseous metastases (22%). The measurement of estrogen receptors will add significantly to selecting patients for this therapy. Since the quality of these responses is high-grade, such therapy should be considered seriously as primary endocrine therapy before cytotoxic chemotherapy is employed. The role of combined hormonal and chemotherapy currently is being explored. The most commonly employed estrogenic hormone is non-enteric coated diethylstilbestrol, 5 mg three times a day. At the initiation of therapy, nausea and occasionally vomiting may occur for a few days, but are not indications for discontinuing therapy. Nausea and vomiting with progressive lethargy and/or polyuria are symptoms of hypercalcemia that may occur at initiation of therapy. This no longer is an indication for discontinuing therapy. The hypercalcemia can be controlled by intermittent use of mithramycin until an antitumor effect occurs. A common systemic effect of estrogen therapy is
May-June
1978, Vol. 4, Nb. 5 and No. 6
fluid retention, which can be controlled by sodium restriction and the use of diuretics. Urinary incontinence may occur because of a loss of bladder tone from the estrogen. Patients who respond to estrogen therapy usually also respond to other modalities of endocrine therapy. These are employed when the metastatic cancer reactivates. The histological changes of breast cancer undergoing regression from estrogen (or androgen) therapy closely resemble those seen following radiation therapy.3 The end product is a dense fibrous reaction. When radiation therapy is employed in postmenopausal patients as an initial therapy for recurrent breast cancer in the skin or for an inoperable primary tumor, the rate of regression for subsequent estrogen therapy is therapy reduced almost by half.” Hence, endocrine should be considered prior to radiotherapy. Moreover, when endocrine therapy induces a regression of the tumor (with resulting fibrosis), subsequent radiation therapy for reactivated tumor in the same area should be undertaken cautiously. Under such circumstances, the radiotherapy is being administered to an area of fibrosis that is similar to one where radiotherapy had been applied previously.
Androgens The androgenic hormones have been employed in all women with metastatic breast cancer. Although they are effective in premenopausal women, the incidence of regressions is less than that from castration. Hence, androgens have no practical role in metastatic breast cancer in premenopausal women. Regressions occur in 21% of postmenopausal women.’ When compared to estrogens, the rate of regression is similar for those with osseous metastases only. For soft tissue or pulmonary lesions, the response rate is less than with estrogens.2.6 Hence, the role of androgens is relatively minor. Androgens may be employed if the tumor in a premenopausal patient responded to castration or if the tumor in a postmenopausal woman responded to estrogens, and if the patient is asymptomatic upon reactivation of disease. Occasionally regressions will occur. Several androgens are available. Oral agents such as fluoxymesterone, 10 mg twice a day, or its equivalent, are employed in preference to parenteral androgens. The regression rates are similar. The systemic effects include induced hypercalcemia, fluid retention and masculinization. The androgenic hormones stimulate erythropoiesis. Because of this reaction, androgens have been employed to stimulate hypercellular bone marrow produced by cytotoxic chemotherapy. Patients who do respond to androgens as a primary
New role of endocrine therapy in breast cancer 0 B. J.
endocrine
hormonal
will have therapies.
a high rate
of response
to other
Proges tins Progestins induce objective remissions in 20-25% of postmenopausal women with metastatic breast cancer. The duration of remission is less than with estrogens. Medroxyprogesterone acetate, 200 mg orally every day, is associated with minimal side effects; this is also true with other progestins. This makes progestins especially useful in elderly women who are prone to develop fluid retention with other agents.
Corticosteroids Adrenocorticosteroids have been employed in the management of advanced breast carcinoma as specific anti-tumor agents as well as for the nonspecific beneficial effects. Their use is seldom indicated as a primary endocrine therapy. There is no doubt that the corticosteroids have an anti-tumor effect primarily because of the ACTH suppressive effect and a resulting suppression of adrenal function. These agents are usually used in lieu of hypophysectomy or adrenalectomy when a patient either is too ill to tolerate those ablative procedures or refuses them. The rate of response of approximately 30% is not as great as with the ablative procedures, nor is the duration of remission as long. Pharmacological doses of oral corticosteroids have included prednisone 20-30 mg q8h, dexamethasone 6mg q8h, or cortisone acetate 100 mg q8h. The chronic administration of these agents leads to Cushing’s syndrome and its multiple complications. Because of the anti-inflammatory effects of corticosteroids, they are employed in the treatment of cerebral metastases (reducing peri-tumor cellular edema), pulmonary or liver metastases (with relief of obstruction resulting from reduction of peri-tumor edema), as an adjunct to radiation therapy (to reduce edema or treat radiation pneumonitis), in the treatment of hemolysis, and as supportive therapy because of the increase in well-being, stimulation of appetite and improvement of bone marrow function. The corticosteroids have been employed as one of the agents in combined chemotherapy programs (e.g. S-drug) which probably accounts for some of the initial benefits noted in these programs.
Aminoglutethimide Aminoglutethimide can inhibit the biosynthesis adrenocortical steroids. A significant suppression steroid production occurs by the administration this agent in combination with hydrocortisone SuPPress a compensatory pituitary corticotrophin
of of of to
KENNEDY,
M.D.,
471
secretion. Objective tumor regressions have occurred in patients whose condition was considered suitable for adrenalectomy or hypophysectomy.‘* In principle, this agent produces a medical adrenalectomy. It is relatively non-toxic.
Anti-estrogens Estrogens in physiological doses may accelerate the growth of some breast cancers, usually in those with estrogen receptors. This stimulatory effect appears to result from a direct effect of the hormone on the tumor cell. Since some breast cancer cells rely on the presence of estrogens, tumor growth can be suppressed by removal of estrogens. However, oophorectomy alone does not totally remove the source of endogenous estrogens. A new series of chemical compounds called antiestrogens can block the peripheral function of estrogens on target tissues. The antiestrogens can control breast cancer by competitive binding to the 8s estrogen receptor site. Tamoxifen, 20 mg twice a day orally, produced objective regression in 32% of patients who were treated previously with endocrine therapy.’ The results are similar to that of estrogens when used as initial therapy. The duration of remission is greater than 9 months. The response to Tamoxifen can be predicted more accurately when tumor biological markers (estrogen receptors) and tumor biological behavior (the history of response to previous hormonal therapies) are considered. If a response occurred to previous endocrine therapy, 67% of the patients responded to Tamoxifen. For estrogen receptor positive tumors with a prior response to endocrine therapy, almost all patients can be expected to respond. The systemic effects of Tamoxifen are minimal, primarily because of its basic pharmacological action. By blocking the peripheral function of estrogens, menopausal symptoms such as hot flushes may occur one again in postmenopausal patients. SUMMARY The introduction of the biological marker (estrogen receptor) and the new antiestrogens has stimulated a new look at hormonal therapies of breast cancer with rediscovery of the known beneficial effects. New studies will look at the role of hormonal therapies in the adjuvant treatment of breast cancer and the effects of combined chemotherapy and hormonal therapies. There is no doubt that therapy will become increasingly selective for the individual patient with consideration of the biological markers and biological behavior of breast cancer thereby providing improved control of the disease and perhaps eventually, its cure.
Radiation Oncology 0 Biology 0 Physics
472
May-June
1978, Vol. 4, No. 5 and No. 6
REFERENCES 1. Cooperative Breast Group: Testosterone propionate therapy in breast cancer. J. Am. Med. Assoc. 188: 1069-1072, 1964. 2. Council on Drugs, Subcommittee on Breast and Genital Cancer, Committee on Research, AMA: Androgens and estrogens in the treatment of disseminated mammary carcinoma-retrospective study of 944 patients. J. Am. Med. Assoc. 172: 1271-1283, 1960. 3. Emerson, W.J., Kennedy, B.J., Graham, J.N.: Pathology of primary and recurrent carcinoma of human breast after administration of steroid hormones. Cancer 10: 1055-1057, 1957. 4. Horovitz, K. B. McGuire, W.L.: Specific progesterone receptors in human breast cancer. Steroids 25: 497-505, 1975.
5. Jensen,
E.V.: Estrogen
receptors
in breast
cancer.
J.
Am. Med. Assoc. 238: 59-60, 1977.
6. Kennedy,
B.J.: Hormonal
therapies
Semin. Oncol. 1: 119-130. 1974.
of breast
cancer.
7. Kennedy, B.J., Mielke, P.W., Fortuny, I.E.: Therapeutic castration versus prophylactic castration in breast cancer. Surg. Gynecol. Obstet. 118: 424-540, 1964. 8. Kiang, D.T., Kennedy, B.J.: Factors affecting estrogen receptors in breast cancer. Cancer 40: 1571-1576, 1977. 9. Kiang, D.T., Kennedy, B.J.: Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann. Intern Med. 87: 687-690, 1977. 10. McGuire, W.L., Carbone, P.P., Vollmer, E.P. (eds): Estrogen
Receptor
in Human
Breast
Cancer.
New
York, Raven Press, 1975. 11. Nathanson, I.: Clinical investigative experinece with steroid hormones in breast cancer. Cancer 5: 754-762, 1952. 12. Troner,
Svaraj, N., Fishman, L.: Medical adwith aminoglutethimide in the treatment of metastatic breast cancer. Proc. Am. SOC. Clin. Oncoi. 18: 291, 1977. M.B.,
renalectomy
??Cukrent Concetds in Cancer NEW ROLE OF ENDOCRINE THERAPY IN BREAST CANCERt B. J. KENNEDY,
M.D.
Section of Medical Oncology, Department of Medicine, University of Minnesota School of Medicine, Minneapolis, MN 55455, U.S.A. Estrogen receptors, Hypophysectomy, Estrogens, Androgens, Breast cancer, Corticosteroids.
estrogen receptor assay results requires cognizance of the techniques of collecting tissue and performance of the test. Specific estrogen receptors (ER) are detectable in 50-80% of breast cancers.” The incidence is considerably lower in premenopausal women (29%) than in postmenopausal women (61%).* The low incidence of ER positivity in premenopausal tumors has been attributed to the presence of high endogenous estrogens which occupy the receptor sites. Correlations have been established between the presence of estrogen receptors and the clinical response to hormonal therapy. Of the patients whose tumors contain estrogen receptors, about two thirds respond to hormonal manipulations. This is approximately double the response rate obtained in clinical studies where patients were treated without regard to estrogen receptor data. Of patients whose tumors lack significant estrogen binding activity, the response rate has been less than 5%. Thus, knowledge of estrogen receptor status provides a means to select the indicated hormonal therapy or chemotherapy specifically for an individual patient. Since it is difficult to obtain tissue for analysis of lesions metastatic to the lungs, liver or bones, it would be advantageous to establish the estrogen receptor values of all breast cancers at the time of the initial biopsy or mastectomy. This information would be an invaluable guide to selecting hormonal therapy at the time of recurrence.5 More recent, quantification of progesterone receptors4 or intranuclear estrogen receptors may be of further value in identifying the biologic nature of hormone-responsive tumors.
The growth of specific breast cancers depends upon hormonal factors. This dependence has been demonstrated by the stimulation of growth by small doses of estrogenic hormone and regression of tumor‘ upon withdrawal of estrogens by oophorectomy, or with administration of large doses of estrogenic hormones. The many hormonal factors involved in breast cancer growth are reflected in the therapeutic regulatory concepts of ablative or administered hormonal therapies. Clinical investigations have developed patterns for successive use of the hormonal therapies, primarily depending on the observed responses to each therapy. About 40% of women with recurrent or metastatic breast cancer will benefit from hormonal therapies. The introduction of chemical therapies, especially combination chemotherapies with regression rates exceeding 65%, distracted physicians from employing hormonal therapies. With the realization that despite these high rates the cancer was not being cured, the hormonal therapies have gained attention again. This has been augmented by the effectiveness of the antiestrogenic agents and the role of estrogen receptor proteins (estrophilin) in designating those breast cancers most likely to respond to hormonal manipulations. The estrogen receptor assay results now provide an improved means for individualizing the selection of hormonal or chemical therapies of breast cancer. Estrogen receptors A Guide to Breast Cancer Therapy. Hormone dependence of breast cancer may be predicted by the results of estrogen receptor measurements. The hormone responsive tumors have a cytoplasmic receptor that binds steroid hormone in vitro. Measurements can be made by using labeled estrogens and a specific inhibitor. Interpretation of
ABLATIVE
HORMONAL
THERAPIES
Bilateral salpingo-ovariectomy is the initial treatment of choice for premenopausal patients with metastatic breast carcinoma. Approximately 40% of
tSupported by Research Grants CA-08832, CA-19527 and CB-64000 from the National Cancer Institute, the Min-
nesota Medical Foundation and the Masonic Memorial Hospital Fund, Inc. 469
470
Radiation
Oncology
0 Biology
0 Physics
patients who are unselected on the basis of estrogen receptor measurements, obtain objective remission of disease. The median period of remission is 9-12 months. Patients who do not respond to ovariectomy, or those who do not have estrogen receptors in their tumors, are treated with combined cytotoxic chemotherapy. Castration is not recommended as an adjuvant therapy at the time of mastectomy.’ Hypophysectomy or bilateral adrenalectomy are employed as secondary endocrine therapies. These ablative procedures will induce objective remissions in 70-90% of premenopausal women who respond to castration or in postmenopausal patients who respond to estrogenic or androgenic hormone administration. The median duration of remission has been 12-14 months. If patients are selected who responded to the initial endocrine (castration or therapy estrogenslandrogens) and who have estrogen receptors present in the metastatic tumor, the response rates to hypophysectomy or adrenalectomy may be even higher.
Estrogens In women who are 4 or more years postmenopausal, the administration of estrogenic hormones in pharmacological doses is the primary endocrine therapy for metastatic breast cancer. The objective remission rate is about 35%, with remissions lasting from several months to many years. In a rare patient cure is regarded as having occurred. The site of the metastatic lesions is of paramount importance. For inoperable primary lesions without dissemination beyond the regional nodes, 55% of objective regressions have been reported.” The response rate is less with pulmonary metastases (40%) or osseous metastases (22%). The measurement of estrogen receptors will add significantly to selecting patients for this therapy. Since the quality of these responses is high-grade, such therapy should be considered seriously as primary endocrine therapy before cytotoxic chemotherapy is employed. The role of combined hormonal and chemotherapy currently is being explored. The most commonly employed estrogenic hormone is non-enteric coated diethylstilbestrol, 5 mg three times a day. At the initiation of therapy, nausea and occasionally vomiting may occur for a few days, but are not indications for discontinuing therapy. Nausea and vomiting with progressive lethargy and/or polyuria are symptoms of hypercalcemia that may occur at initiation of therapy. This no longer is an indication for discontinuing therapy. The hypercalcemia can be controlled by intermittent use of mithramycin until an antitumor effect occurs. A common systemic effect of estrogen therapy is
May-June
1978, Vol. 4, Nb. 5 and No. 6
fluid retention, which can be controlled by sodium restriction and the use of diuretics. Urinary incontinence may occur because of a loss of bladder tone from the estrogen. Patients who respond to estrogen therapy usually also respond to other modalities of endocrine therapy. These are employed when the metastatic cancer reactivates. The histological changes of breast cancer undergoing regression from estrogen (or androgen) therapy closely resemble those seen following radiation therapy.3 The end product is a dense fibrous reaction. When radiation therapy is employed in postmenopausal patients as an initial therapy for recurrent breast cancer in the skin or for an inoperable primary tumor, the rate of regression for subsequent estrogen therapy is therapy reduced almost by half.” Hence, endocrine should be considered prior to radiotherapy. Moreover, when endocrine therapy induces a regression of the tumor (with resulting fibrosis), subsequent radiation therapy for reactivated tumor in the same area should be undertaken cautiously. Under such circumstances, the radiotherapy is being administered to an area of fibrosis that is similar to one where radiotherapy had been applied previously.
Androgens The androgenic hormones have been employed in all women with metastatic breast cancer. Although they are effective in premenopausal women, the incidence of regressions is less than that from castration. Hence, androgens have no practical role in metastatic breast cancer in premenopausal women. Regressions occur in 21% of postmenopausal women.’ When compared to estrogens, the rate of regression is similar for those with osseous metastases only. For soft tissue or pulmonary lesions, the response rate is less than with estrogens.2.6 Hence, the role of androgens is relatively minor. Androgens may be employed if the tumor in a premenopausal patient responded to castration or if the tumor in a postmenopausal woman responded to estrogens, and if the patient is asymptomatic upon reactivation of disease. Occasionally regressions will occur. Several androgens are available. Oral agents such as fluoxymesterone, 10 mg twice a day, or its equivalent, are employed in preference to parenteral androgens. The regression rates are similar. The systemic effects include induced hypercalcemia, fluid retention and masculinization. The androgenic hormones stimulate erythropoiesis. Because of this reaction, androgens have been employed to stimulate hypercellular bone marrow produced by cytotoxic chemotherapy. Patients who do respond to androgens as a primary
New role of endocrine therapy in breast cancer 0 B. J.
endocrine
hormonal
will have therapies.
a high rate
of response
to other
Proges tins Progestins induce objective remissions in 20-25% of postmenopausal women with metastatic breast cancer. The duration of remission is less than with estrogens. Medroxyprogesterone acetate, 200 mg orally every day, is associated with minimal side effects; this is also true with other progestins. This makes progestins especially useful in elderly women who are prone to develop fluid retention with other agents.
Corticosteroids Adrenocorticosteroids have been employed in the management of advanced breast carcinoma as specific anti-tumor agents as well as for the nonspecific beneficial effects. Their use is seldom indicated as a primary endocrine therapy. There is no doubt that the corticosteroids have an anti-tumor effect primarily because of the ACTH suppressive effect and a resulting suppression of adrenal function. These agents are usually used in lieu of hypophysectomy or adrenalectomy when a patient either is too ill to tolerate those ablative procedures or refuses them. The rate of response of approximately 30% is not as great as with the ablative procedures, nor is the duration of remission as long. Pharmacological doses of oral corticosteroids have included prednisone 20-30 mg q8h, dexamethasone 6mg q8h, or cortisone acetate 100 mg q8h. The chronic administration of these agents leads to Cushing’s syndrome and its multiple complications. Because of the anti-inflammatory effects of corticosteroids, they are employed in the treatment of cerebral metastases (reducing peri-tumor cellular edema), pulmonary or liver metastases (with relief of obstruction resulting from reduction of peri-tumor edema), as an adjunct to radiation therapy (to reduce edema or treat radiation pneumonitis), in the treatment of hemolysis, and as supportive therapy because of the increase in well-being, stimulation of appetite and improvement of bone marrow function. The corticosteroids have been employed as one of the agents in combined chemotherapy programs (e.g. S-drug) which probably accounts for some of the initial benefits noted in these programs.
Aminoglutethimide Aminoglutethimide can inhibit the biosynthesis adrenocortical steroids. A significant suppression steroid production occurs by the administration this agent in combination with hydrocortisone SuPPress a compensatory pituitary corticotrophin
of of of to
KENNEDY,
M.D.,
471
secretion. Objective tumor regressions have occurred in patients whose condition was considered suitable for adrenalectomy or hypophysectomy.‘* In principle, this agent produces a medical adrenalectomy. It is relatively non-toxic.
Anti-estrogens Estrogens in physiological doses may accelerate the growth of some breast cancers, usually in those with estrogen receptors. This stimulatory effect appears to result from a direct effect of the hormone on the tumor cell. Since some breast cancer cells rely on the presence of estrogens, tumor growth can be suppressed by removal of estrogens. However, oophorectomy alone does not totally remove the source of endogenous estrogens. A new series of chemical compounds called antiestrogens can block the peripheral function of estrogens on target tissues. The antiestrogens can control breast cancer by competitive binding to the 8s estrogen receptor site. Tamoxifen, 20 mg twice a day orally, produced objective regression in 32% of patients who were treated previously with endocrine therapy.’ The results are similar to that of estrogens when used as initial therapy. The duration of remission is greater than 9 months. The response to Tamoxifen can be predicted more accurately when tumor biological markers (estrogen receptors) and tumor biological behavior (the history of response to previous hormonal therapies) are considered. If a response occurred to previous endocrine therapy, 67% of the patients responded to Tamoxifen. For estrogen receptor positive tumors with a prior response to endocrine therapy, almost all patients can be expected to respond. The systemic effects of Tamoxifen are minimal, primarily because of its basic pharmacological action. By blocking the peripheral function of estrogens, menopausal symptoms such as hot flushes may occur one again in postmenopausal patients. SUMMARY The introduction of the biological marker (estrogen receptor) and the new antiestrogens has stimulated a new look at hormonal therapies of breast cancer with rediscovery of the known beneficial effects. New studies will look at the role of hormonal therapies in the adjuvant treatment of breast cancer and the effects of combined chemotherapy and hormonal therapies. There is no doubt that therapy will become increasingly selective for the individual patient with consideration of the biological markers and biological behavior of breast cancer thereby providing improved control of the disease and perhaps eventually, its cure.
Radiation Oncology 0 Biology 0 Physics
472
May-June
1978, Vol. 4, No. 5 and No. 6
REFERENCES 1. Cooperative Breast Group: Testosterone propionate therapy in breast cancer. J. Am. Med. Assoc. 188: 1069-1072, 1964. 2. Council on Drugs, Subcommittee on Breast and Genital Cancer, Committee on Research, AMA: Androgens and estrogens in the treatment of disseminated mammary carcinoma-retrospective study of 944 patients. J. Am. Med. Assoc. 172: 1271-1283, 1960. 3. Emerson, W.J., Kennedy, B.J., Graham, J.N.: Pathology of primary and recurrent carcinoma of human breast after administration of steroid hormones. Cancer 10: 1055-1057, 1957. 4. Horovitz, K. B. McGuire, W.L.: Specific progesterone receptors in human breast cancer. Steroids 25: 497-505, 1975.
5. Jensen,
E.V.: Estrogen
receptors
in breast
cancer.
J.
Am. Med. Assoc. 238: 59-60, 1977.
6. Kennedy,
B.J.: Hormonal
therapies
Semin. Oncol. 1: 119-130. 1974.
of breast
cancer.
7. Kennedy, B.J., Mielke, P.W., Fortuny, I.E.: Therapeutic castration versus prophylactic castration in breast cancer. Surg. Gynecol. Obstet. 118: 424-540, 1964. 8. Kiang, D.T., Kennedy, B.J.: Factors affecting estrogen receptors in breast cancer. Cancer 40: 1571-1576, 1977. 9. Kiang, D.T., Kennedy, B.J.: Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann. Intern Med. 87: 687-690, 1977. 10. McGuire, W.L., Carbone, P.P., Vollmer, E.P. (eds): Estrogen
Receptor
in Human
Breast
Cancer.
New
York, Raven Press, 1975. 11. Nathanson, I.: Clinical investigative experinece with steroid hormones in breast cancer. Cancer 5: 754-762, 1952. 12. Troner,
Svaraj, N., Fishman, L.: Medical adwith aminoglutethimide in the treatment of metastatic breast cancer. Proc. Am. SOC. Clin. Oncoi. 18: 291, 1977. M.B.,
renalectomy
