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Role of bilateral adrenalectomy (and oophorectomy) in the management of patients with metastatic breast cancer
Role of Bilateral Adrenalectomy (and Oophorectomy) in the Management of Patients with Metastatic Breast Cancer
James E. Devitt, MD, CM, MSc, FRCS (Ed), FRCS(C), Ottawa, Ontario, Canada James M. Hardwick, MB, FRCS (Glas), FRCS(C), Ottawa, Ontario, Canada
That bilateral adrenalectomy (and oophorectomy) has a place in the management of metastatic breast cancer has been realized since the pioneer report of Huggins and Bergenstal [I]. Just what that place is has been somewhat confused by the many other forms of therapy that have become available. To clarify the role of this operation and to examine the results that can be expected from it, this report analyzes 100 consecutive patients who were subjected to adrenalectomy (and oophorectomy) for metastatic breast cancer. Material and Methods All patients underwent bilateral adrenalectomy (and oophorectomy) for metastatic breast cancer performed by one of us (JED) between March 1968 and January 1977. The patients were referred by the radiation and medical oncologists of the Civic Hospital Division, Ottawa Clinic of the Ontario Cancer Foundation. They constitute most of the patients subjected to the operation and followed up in this clinic. The patients were carefully selected; all had symptomatic metastatic breast cancer. Except for eight patients who had symptomatic metastases at the time of their first presentation with breast cancer and one patient for whom the interval between mastectomy and adrenalectomy (and oophorectomy) was 21 months, all patients had had at least a 24 month period between mastectomy and the appearance of metastases. Liver metastases were considered a contraindication to adrenalectomy, except in 27 patients who were found at laparotomy to have a few tiny or occasional hepatic secondary lesions. Cerebral metastases and pulmonary metastases of the “lymphangitic” type were contraindications to the operation. Thus, the patients From the Civic Hospital Division, Ottawa Clinic of the Ontario Cancer Foundation and the Departments of Surgery, Ottawa Civic Hospital and University of Ottawa, Ottawa, Ontario, Canada. Reprint requests should be addressed to J. E. Devitt, MD, Medical Education, Ottawa Civic Hospital, 1053 Carllng Avenue, Ottawa, Ontario, Canada KIY 4E9.
Volume 137, May 1979
operated on had bony or local-regional metastases, pleural effusions, or discrete pulmonary or mediastinal metastases. The degree of selection is indicated by the fact that although 150 to 225 new patients with primary breast cancer were seen at the clinic annually, only approximately 12 bilateral adrenalectomies (and oophorectomies) were performed each year. All operations were performed in a single stage using a low left paramedian incision for bilateral oophorectomy and preliminary laparotomy and an anterior subcostal chevron incision for bilateral adrenalectomy. Except in one patient who had previously had unilateral oophorectomy and hysterectomy and whose remaining ovary had been irradiated, the ovaries, if present, were removed at the time of adrenalectomy. No cortisone was given preoperatively. Postoperatively the patients were managed with 400, 300, and 200 mg of cortisone intravenously during the first three 24 hour periods. Thereafter, they were usually managed on 25 mg of cortisone orally, adding salt generously to their food. Many patients adjusted their dosage from 37.5 to 75 mg daily depending on individual response. Occasionally fludrocortisone or prednisone was used. For this review we have tried to apply the response criteria of Hayward et al [2] in evaluating the outcome of adrenalectomy (and oophorectomy). However, the notation by the radiation or medical oncologist that earlier or subsequent therapy produced worthwhile palliation was accepted as indicating a response at that time. All patients were followed up by the staff of the Civic Hospital Division, Ottawa Clinic of the Ontario Cancer Foundation, or at other cancer clinics for patients who moved, until May 1978, for a minimum follow-up period of 15 months. Results
There was one postoperative death, on the 24th postoperative day. In this patient the pleural effusions and pulmonary metastases did not respond to the operation. The resulting respiratory failure was treated with local nitrogen mustard, which induced
629
Devitt and Hardwick
The likelihood of response was equal at all ages (Table II). Patients over 60 years of age had a particularly good response rate. The median duration of response was similar at all ages. The likelihood of response was better if the time interval between the original therapy and bilateral adrenalectomy (and oophorectomy) was 5 years or more (Table III). The median duration of response was similar no matter what the time interval between mastectomy and adrenalectomy. The likelihood of response was similar for all sites of metastases for which adrenalectomy (and oophorectomy) was considered indicated (Table IV). Patients with involvement of multiple (acceptable) organs or sites did as well as did those whose disease was confined to a single tissue or system. The median duration of response was similar for all sites. If the liver was found to be significantly involved at initial laparotomy, bilateral adrenalectomy was not carried out. However, isolated or tiny metastases were found in 28 patients, and adrenalectomy was performed. Fourteen of those women (SO per cent) had regressions of 9 to 36 months with a median of 15 months. Cade [3] has reported a similar experience. When bilateral adrenalectomy (and oophorectomy) was the first therapy for metastases, it was more likely to be followed by regression than was treatment other than local excision of recurrence (Table V). Response to previous hormonal manipu-
Months Figure 7. Survival and remission rates afler adrenalectomy.
an Addisonian crisis that was followed by renal failure. The postoperative length of stay varied from 5 to 253 days, the median day of discharge was the 10th day, and 80 per cent of patients were discharged by the 14th day. The length of stay was largely determined by the response of the patient’s metastatic disease. Two-thirds of the patients (65) obtained an objective remission of at least 6 months. Nine of these were partial regressions. The duration of remission is seen in Table I. Only one-half the women obtained a remission lasting 1 year, and only one-sixth a remission lasting 2 years. The median duration of response was 15 months. The total survival after adrenalectomy (and oophorectomy) is seen in Figure 1.
TABLE I
Percentage of Patients in Remission After Bilateral Adrenalectomy
Patients
6
9
12
Percentage No.
65 100
57 100
48 100
TABLE II
Duration of Remission (mo) 15 18 36 95
28 91
24
30
36
16 aa
11 a5
7 al
Relation of Response to Adrenalectomy to Age of Patient Age (yr)
Patients
<39
No. responding No. of patients
3 4
TABLE III
40-44 a 13
50-54
17 29
55-59
11 17
60-64
9 15
10 13
>65 7 9
Relation of Response to Interval Between Mastectomy and Adrenalectomy
Patients
0
<24
No. responding No. of patients
4 6
1 1
630
45-49
24-35 13 ia
36-47 9 20
Interval (mo) 48-59 a 14
13 17
7 11
10 11
The American Journal of Surgery
Metastatic Breast Cancer
lation (including androgen, estrogen, and prednisone therapy and surgical or radiation castration) bore no relation to the response to subsequent adrenalectomy (and oophorectomy). Menopausal status did not correlate well with response. Six of 27 patients who were menstruating and 28 of 72 patients who had either natural or artificial menopause failed to respond. There was one nonresponding 49 year old patient whose records did not indicate menstrual status. When the remission ended, the disease was as likely to reactivate at new sites as at the previous sites for which the adrenalectomy (and oophorectomy) had been performed. In 24 of the 65 patients who had remission new metastases developed, whereas in 27 patients the original metastases were the site of reactivation (8 patients are still in remission, and 5 patients died of breast cancer after leaving Ottawa with no further available information). After relapse or failure to respond to adrenalectomy (and oophorectomy), patients frequently received palliation with further therapy including chemotherapy (29 of 56 patients), radiotherapy (37 of 54 patients), and endocrine additive therapy (4 of 13 patients). No further treatment or no information was given in eight patients, and nine patients are still in remission. Many patients responded to more than one kind of additional therapy (response here being 3 months of symptomatic relief). The median survival of patients not responding to bilateral adrenalectomy (and oophorectomy) was 14 months. The median survival after relapse and after a successful response to adrenalectomy (and oophorectomy) was 9 months.
TABLE IV
Bilateral adrenalectomy (and oophorectomy) for metastatic breast cancer can be performed with minimal morbidity and mortality. Undoubtedly this is most likely to be achieved if all or at least most of the experience in a clinic or hospital is concentrated to one or two surgeons. Only when such concentration occurs can experience be gained to allow better selection of patients and more informed operative and postoperative management. The one hospital death in this series occurred from complications of further therapy and from the unremitting progress of the disease, although there is no doubt that the adrenalectomized state contributed significantly to the complications. Indeed the quality of remission, when it occurs, is best after adrenalectomy and the relief of symptoms is usually the longest, with fewer and shorter follow-up visits required. Moreover, once the immediate postoperative distress is passed, the therapy-induced morbidity is minimal, unlike that of most chemotherapeutic and many additive hormonal regimens. The key to the use of bilateral adrenalectomy (and oophorectomy) is the careful selection of patients. In this series the criteria for selection were symptomatic metastases in sites likely to respond (local-regional, bony, pleural, and pulmonary sites that were not lymphangitic) with at least a 2 year interval between mastectomy and the appearance of metastases. With these criteria a successful remission rate of 65 per cent was achieved. The rigid application of these requirements and the exclusion of patients with cerebral or significant liver metastases or with less than
Relation of Response to Site of Metastases
Patients No. responding No. of patients
TABLE V
Comments
Localf Regional Alone
Locall Regional Plus Other
Pleural Effusion Alone
5 7
16 23
4 7
Site Pleural Effusion Plus Other 16 19
Pulmonary/ Mediastinal Alone
Pulmonary/ Mediastinal Plus Other
1 2
10 12
Bony Alone
Bony Plus Other
29 46
17 27
Relation of Response to Previous Therapy
Patients No. responding No. of patients
Volume137,May1979
No Previous Therapy 45 63
Surgical Excision 12 16
Radiotherapy 6 17
Previous Therapy Response to Previous Endocrine Manipulation 5 12
No Response to Previous Endocrine Manipulation 5 8
Chemotherapy 2 3
631
Devitt
and Hardwick
a 2 year “free interval” undoubtedly account for the improved results over the 30 to 40 per cent response rate in adrenalectomy series in which the patients are not selected [4-61. The outcome was not influenced by the patient’s menstrual status. Also, older age was not a contraindication in patients who were otherwise fit. Although it is commonly believed that the previous response to endocrine manipulation can be used to predict the response to adrenalectomy, many reports of major endocrine ablation do not support this belief [3,7-g]. The present series too showed that the response to adrenalectomy (and oophorectomy) bore no correlation to earlier endocrine therapy (surgical or radiation castration or androgen, estrogen, or prednisone therapy). Although in many adrenalectomy series there is a good correlation between the response to oophorectomy and the response to subsequent adrenalectomy, this is less obvious in many others [7,8,10,11]. Cade [3] suggested that this is true because the patients’ response to initial hormone manipulation is always better than the response to later therapy, an observation confirmed by this study. In general, if adrenalectomy is to be performed at all, it should be done early in the course of metastatic breast cancer. It does not obviate the treatment of small, localized initial metastases with radiation, excision, or additive hormones when this seems appropriate, based on the likelihood of controlling symptoms. The increasing availability of assays of steroid receptors may have a tendency to seduce practitioners into depending on this test to make the decision to ablate rather than using it to supplement the clinical data that can identify, at least as successfully, those patients likely to respond. Jensen et al [IL’], using a different critical level of tumor estrophilin content in premenopausal than in postmenopausal or castrated women, were able to observe that in a series of 58 patients undergoing adrenalectomy, 62 per cent of patients with positive receptor test results and only 3 per cent of patients with borderline and negative test results had regression. However, McGuire et al [13] suggest that a patient with a positive test result has a 55 per cent chance of responding to endocrine ablation, a patient with a borderline test result a 30 per cent chance, and a patient with a negative test result an 8 per cent chance. Assuming that the average laboratory can meet this degree of accuracy, it is clearly necessary to continue the use of clinical assessment in identifying patients for adrenalectomy (and oophorectomy) [9] as well as assay receptor studies when available. As in other clinical problems, all available information should be utilized. 632
The observation [2] that in one-half the responding patients the site of reactivation was not known to be involved at the time of adrenalectomy (and oophorectomy) whereas the original metastatic site(s) may remain in remission even until death is confirmed but not readily explained. Although adrenalectomy (and oophorectomy) does not cure breast cancer, it frequently seems to be associated with a “cure” of some metastases. Bilateral adrenalectomy (and oophorectomy) then has a role in the management of carefully selected patients with metastatic breast cancer. It is the method of choice for fit patients with symptomatic bony, pleural, or discrete pulmonary or mediastinal metastases who have had a 2 year “tumor-free” interval after primary treatment as well as those with local or regional metastases that cannot be managed by simpler methods. An experienced team will have minimal morbidity, and a remission will be gained in two-thirds of the patients for a 10 day hospitalization and a further 3 week convalescence at home. The median duration of remission will be 15 months. After relapse, further palliation can be achieved by other therapeutic measures in at least two-thirds of the patients, with a further median survival of 9 months. Summary
One hundred consecutive patients who underwent bilateral adrenalectomy for metastatic breast cancer with at least a 2 year “tumor-free” interval and with symptomatic bony, local-regional, pleural, or discrete pulmonary or mediastinal metastases had objective remission rates of 65 per cent at 6 months, 48 per cent at 12 months, 28 per cent at 18 months, and 16 per cent at 24 months. References 1. Huggins C, Bergen&l DM: Surgery of the adrenals. JAMA 147: 101.1951. 2. Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer. Cancer 39: 1289, 1977. 3. Cade S: Adrenalectomy for disseminated breast cancer. 8r A&d J 2: 613, 1966. 4. MacDonald I: Endocrine ablation in disseminated mammary carcinoma. Surg Gynecol Obstet 115: 215, 1962. 5. Fracchia AA, Randall HT. Farrow JH: The results of adrenalectomy in advanced breast cancer in 500 consecutive patients. Surg Gynecol Obstet 125: 747, 1967. 6. Moore FD, Van Devanter SB, Boyden CM, Lokich J, Wilson RD: Adrenalectomy with chemotherapy in the treatment of advanced breast cancer: objective and subjective resoonse rates; duration and quality-of life. Surgej76: 376, i974. 7. Dao TL, Nemoto T, Bross I: A controlled randomized comoarative study of early and late adrenalectomy in women with advanced breast cancer, p 177. Prognostic Factors in Breast Cancer. Forrest APM, Kunkler PB, ed. Edinburgh and London, E. & S. Livingstone Ltd. 1968.
The American Journal of Surgery
Metastatic
8. Fracchia AA, Farrow JH, Miller TR, Tollefesen HR. Greenberg, EJ, Knapper WH: Hypophysectorny as compared with adrenalectomy in the treatment of advanced carcinoma of the breast. Surg Gynecot Obstet 133: 241, 1971. 9. Leaper DJ: A clinical index for selection of breast cancer patients for adrenalectomy. Br J Surg 63: 759, 1976. 10. Brown PW, Terg JJ, King R, Lawrence J: Bilateral adrenalectomy for metastatic breast cancer. Arch Sorg 110: 77, 1975. 11. Silverstein MJ, Byron RL, Yonemoto RH, Riihimaki DU, Schuster
Volume137,
May
1979
Breast
Cancer
G: Bilateral adrenalectomy for advanced breast cancer: a 21 year experience. Surgery 77: 825, 1975. 12. Jensen EV, Smith S, De Sombre ER: Hormone dependency in breast cancer, p 131. Progress in Clinical and Biological Research, vol. 12. Breast Cancer (Montague ACW, Stonesifer GL, Lewison EF, ed). New York, Alan R. Liss Inc., 1977. 13. McGuire WL, Horowitz KB, Pearson DH, Segaloff A: Current status of estrogen and progesterone receptors in breast cancer. Cancer 39: 2934, 1977.
633
James E. Devitt, MD, CM, MSc, FRCS (Ed), FRCS(C), Ottawa, Ontario, Canada James M. Hardwick, MB, FRCS (Glas), FRCS(C), Ottawa, Ontario, Canada
That bilateral adrenalectomy (and oophorectomy) has a place in the management of metastatic breast cancer has been realized since the pioneer report of Huggins and Bergenstal [I]. Just what that place is has been somewhat confused by the many other forms of therapy that have become available. To clarify the role of this operation and to examine the results that can be expected from it, this report analyzes 100 consecutive patients who were subjected to adrenalectomy (and oophorectomy) for metastatic breast cancer. Material and Methods All patients underwent bilateral adrenalectomy (and oophorectomy) for metastatic breast cancer performed by one of us (JED) between March 1968 and January 1977. The patients were referred by the radiation and medical oncologists of the Civic Hospital Division, Ottawa Clinic of the Ontario Cancer Foundation. They constitute most of the patients subjected to the operation and followed up in this clinic. The patients were carefully selected; all had symptomatic metastatic breast cancer. Except for eight patients who had symptomatic metastases at the time of their first presentation with breast cancer and one patient for whom the interval between mastectomy and adrenalectomy (and oophorectomy) was 21 months, all patients had had at least a 24 month period between mastectomy and the appearance of metastases. Liver metastases were considered a contraindication to adrenalectomy, except in 27 patients who were found at laparotomy to have a few tiny or occasional hepatic secondary lesions. Cerebral metastases and pulmonary metastases of the “lymphangitic” type were contraindications to the operation. Thus, the patients From the Civic Hospital Division, Ottawa Clinic of the Ontario Cancer Foundation and the Departments of Surgery, Ottawa Civic Hospital and University of Ottawa, Ottawa, Ontario, Canada. Reprint requests should be addressed to J. E. Devitt, MD, Medical Education, Ottawa Civic Hospital, 1053 Carllng Avenue, Ottawa, Ontario, Canada KIY 4E9.
Volume 137, May 1979
operated on had bony or local-regional metastases, pleural effusions, or discrete pulmonary or mediastinal metastases. The degree of selection is indicated by the fact that although 150 to 225 new patients with primary breast cancer were seen at the clinic annually, only approximately 12 bilateral adrenalectomies (and oophorectomies) were performed each year. All operations were performed in a single stage using a low left paramedian incision for bilateral oophorectomy and preliminary laparotomy and an anterior subcostal chevron incision for bilateral adrenalectomy. Except in one patient who had previously had unilateral oophorectomy and hysterectomy and whose remaining ovary had been irradiated, the ovaries, if present, were removed at the time of adrenalectomy. No cortisone was given preoperatively. Postoperatively the patients were managed with 400, 300, and 200 mg of cortisone intravenously during the first three 24 hour periods. Thereafter, they were usually managed on 25 mg of cortisone orally, adding salt generously to their food. Many patients adjusted their dosage from 37.5 to 75 mg daily depending on individual response. Occasionally fludrocortisone or prednisone was used. For this review we have tried to apply the response criteria of Hayward et al [2] in evaluating the outcome of adrenalectomy (and oophorectomy). However, the notation by the radiation or medical oncologist that earlier or subsequent therapy produced worthwhile palliation was accepted as indicating a response at that time. All patients were followed up by the staff of the Civic Hospital Division, Ottawa Clinic of the Ontario Cancer Foundation, or at other cancer clinics for patients who moved, until May 1978, for a minimum follow-up period of 15 months. Results
There was one postoperative death, on the 24th postoperative day. In this patient the pleural effusions and pulmonary metastases did not respond to the operation. The resulting respiratory failure was treated with local nitrogen mustard, which induced
629
Devitt and Hardwick
The likelihood of response was equal at all ages (Table II). Patients over 60 years of age had a particularly good response rate. The median duration of response was similar at all ages. The likelihood of response was better if the time interval between the original therapy and bilateral adrenalectomy (and oophorectomy) was 5 years or more (Table III). The median duration of response was similar no matter what the time interval between mastectomy and adrenalectomy. The likelihood of response was similar for all sites of metastases for which adrenalectomy (and oophorectomy) was considered indicated (Table IV). Patients with involvement of multiple (acceptable) organs or sites did as well as did those whose disease was confined to a single tissue or system. The median duration of response was similar for all sites. If the liver was found to be significantly involved at initial laparotomy, bilateral adrenalectomy was not carried out. However, isolated or tiny metastases were found in 28 patients, and adrenalectomy was performed. Fourteen of those women (SO per cent) had regressions of 9 to 36 months with a median of 15 months. Cade [3] has reported a similar experience. When bilateral adrenalectomy (and oophorectomy) was the first therapy for metastases, it was more likely to be followed by regression than was treatment other than local excision of recurrence (Table V). Response to previous hormonal manipu-
Months Figure 7. Survival and remission rates afler adrenalectomy.
an Addisonian crisis that was followed by renal failure. The postoperative length of stay varied from 5 to 253 days, the median day of discharge was the 10th day, and 80 per cent of patients were discharged by the 14th day. The length of stay was largely determined by the response of the patient’s metastatic disease. Two-thirds of the patients (65) obtained an objective remission of at least 6 months. Nine of these were partial regressions. The duration of remission is seen in Table I. Only one-half the women obtained a remission lasting 1 year, and only one-sixth a remission lasting 2 years. The median duration of response was 15 months. The total survival after adrenalectomy (and oophorectomy) is seen in Figure 1.
TABLE I
Percentage of Patients in Remission After Bilateral Adrenalectomy
Patients
6
9
12
Percentage No.
65 100
57 100
48 100
TABLE II
Duration of Remission (mo) 15 18 36 95
28 91
24
30
36
16 aa
11 a5
7 al
Relation of Response to Adrenalectomy to Age of Patient Age (yr)
Patients
<39
No. responding No. of patients
3 4
TABLE III
40-44 a 13
50-54
17 29
55-59
11 17
60-64
9 15
10 13
>65 7 9
Relation of Response to Interval Between Mastectomy and Adrenalectomy
Patients
0
<24
No. responding No. of patients
4 6
1 1
630
45-49
24-35 13 ia
36-47 9 20
Interval (mo) 48-59 a 14
13 17
7 11
10 11
The American Journal of Surgery
Metastatic Breast Cancer
lation (including androgen, estrogen, and prednisone therapy and surgical or radiation castration) bore no relation to the response to subsequent adrenalectomy (and oophorectomy). Menopausal status did not correlate well with response. Six of 27 patients who were menstruating and 28 of 72 patients who had either natural or artificial menopause failed to respond. There was one nonresponding 49 year old patient whose records did not indicate menstrual status. When the remission ended, the disease was as likely to reactivate at new sites as at the previous sites for which the adrenalectomy (and oophorectomy) had been performed. In 24 of the 65 patients who had remission new metastases developed, whereas in 27 patients the original metastases were the site of reactivation (8 patients are still in remission, and 5 patients died of breast cancer after leaving Ottawa with no further available information). After relapse or failure to respond to adrenalectomy (and oophorectomy), patients frequently received palliation with further therapy including chemotherapy (29 of 56 patients), radiotherapy (37 of 54 patients), and endocrine additive therapy (4 of 13 patients). No further treatment or no information was given in eight patients, and nine patients are still in remission. Many patients responded to more than one kind of additional therapy (response here being 3 months of symptomatic relief). The median survival of patients not responding to bilateral adrenalectomy (and oophorectomy) was 14 months. The median survival after relapse and after a successful response to adrenalectomy (and oophorectomy) was 9 months.
TABLE IV
Bilateral adrenalectomy (and oophorectomy) for metastatic breast cancer can be performed with minimal morbidity and mortality. Undoubtedly this is most likely to be achieved if all or at least most of the experience in a clinic or hospital is concentrated to one or two surgeons. Only when such concentration occurs can experience be gained to allow better selection of patients and more informed operative and postoperative management. The one hospital death in this series occurred from complications of further therapy and from the unremitting progress of the disease, although there is no doubt that the adrenalectomized state contributed significantly to the complications. Indeed the quality of remission, when it occurs, is best after adrenalectomy and the relief of symptoms is usually the longest, with fewer and shorter follow-up visits required. Moreover, once the immediate postoperative distress is passed, the therapy-induced morbidity is minimal, unlike that of most chemotherapeutic and many additive hormonal regimens. The key to the use of bilateral adrenalectomy (and oophorectomy) is the careful selection of patients. In this series the criteria for selection were symptomatic metastases in sites likely to respond (local-regional, bony, pleural, and pulmonary sites that were not lymphangitic) with at least a 2 year interval between mastectomy and the appearance of metastases. With these criteria a successful remission rate of 65 per cent was achieved. The rigid application of these requirements and the exclusion of patients with cerebral or significant liver metastases or with less than
Relation of Response to Site of Metastases
Patients No. responding No. of patients
TABLE V
Comments
Localf Regional Alone
Locall Regional Plus Other
Pleural Effusion Alone
5 7
16 23
4 7
Site Pleural Effusion Plus Other 16 19
Pulmonary/ Mediastinal Alone
Pulmonary/ Mediastinal Plus Other
1 2
10 12
Bony Alone
Bony Plus Other
29 46
17 27
Relation of Response to Previous Therapy
Patients No. responding No. of patients
Volume137,May1979
No Previous Therapy 45 63
Surgical Excision 12 16
Radiotherapy 6 17
Previous Therapy Response to Previous Endocrine Manipulation 5 12
No Response to Previous Endocrine Manipulation 5 8
Chemotherapy 2 3
631
Devitt
and Hardwick
a 2 year “free interval” undoubtedly account for the improved results over the 30 to 40 per cent response rate in adrenalectomy series in which the patients are not selected [4-61. The outcome was not influenced by the patient’s menstrual status. Also, older age was not a contraindication in patients who were otherwise fit. Although it is commonly believed that the previous response to endocrine manipulation can be used to predict the response to adrenalectomy, many reports of major endocrine ablation do not support this belief [3,7-g]. The present series too showed that the response to adrenalectomy (and oophorectomy) bore no correlation to earlier endocrine therapy (surgical or radiation castration or androgen, estrogen, or prednisone therapy). Although in many adrenalectomy series there is a good correlation between the response to oophorectomy and the response to subsequent adrenalectomy, this is less obvious in many others [7,8,10,11]. Cade [3] suggested that this is true because the patients’ response to initial hormone manipulation is always better than the response to later therapy, an observation confirmed by this study. In general, if adrenalectomy is to be performed at all, it should be done early in the course of metastatic breast cancer. It does not obviate the treatment of small, localized initial metastases with radiation, excision, or additive hormones when this seems appropriate, based on the likelihood of controlling symptoms. The increasing availability of assays of steroid receptors may have a tendency to seduce practitioners into depending on this test to make the decision to ablate rather than using it to supplement the clinical data that can identify, at least as successfully, those patients likely to respond. Jensen et al [IL’], using a different critical level of tumor estrophilin content in premenopausal than in postmenopausal or castrated women, were able to observe that in a series of 58 patients undergoing adrenalectomy, 62 per cent of patients with positive receptor test results and only 3 per cent of patients with borderline and negative test results had regression. However, McGuire et al [13] suggest that a patient with a positive test result has a 55 per cent chance of responding to endocrine ablation, a patient with a borderline test result a 30 per cent chance, and a patient with a negative test result an 8 per cent chance. Assuming that the average laboratory can meet this degree of accuracy, it is clearly necessary to continue the use of clinical assessment in identifying patients for adrenalectomy (and oophorectomy) [9] as well as assay receptor studies when available. As in other clinical problems, all available information should be utilized. 632
The observation [2] that in one-half the responding patients the site of reactivation was not known to be involved at the time of adrenalectomy (and oophorectomy) whereas the original metastatic site(s) may remain in remission even until death is confirmed but not readily explained. Although adrenalectomy (and oophorectomy) does not cure breast cancer, it frequently seems to be associated with a “cure” of some metastases. Bilateral adrenalectomy (and oophorectomy) then has a role in the management of carefully selected patients with metastatic breast cancer. It is the method of choice for fit patients with symptomatic bony, pleural, or discrete pulmonary or mediastinal metastases who have had a 2 year “tumor-free” interval after primary treatment as well as those with local or regional metastases that cannot be managed by simpler methods. An experienced team will have minimal morbidity, and a remission will be gained in two-thirds of the patients for a 10 day hospitalization and a further 3 week convalescence at home. The median duration of remission will be 15 months. After relapse, further palliation can be achieved by other therapeutic measures in at least two-thirds of the patients, with a further median survival of 9 months. Summary
One hundred consecutive patients who underwent bilateral adrenalectomy for metastatic breast cancer with at least a 2 year “tumor-free” interval and with symptomatic bony, local-regional, pleural, or discrete pulmonary or mediastinal metastases had objective remission rates of 65 per cent at 6 months, 48 per cent at 12 months, 28 per cent at 18 months, and 16 per cent at 24 months. References 1. Huggins C, Bergen&l DM: Surgery of the adrenals. JAMA 147: 101.1951. 2. Hayward JL, Carbone PP, Heuson JC, Kumaoka S, Segaloff A, Rubens RD: Assessment of response to therapy in advanced breast cancer. Cancer 39: 1289, 1977. 3. Cade S: Adrenalectomy for disseminated breast cancer. 8r A&d J 2: 613, 1966. 4. MacDonald I: Endocrine ablation in disseminated mammary carcinoma. Surg Gynecol Obstet 115: 215, 1962. 5. Fracchia AA, Randall HT. Farrow JH: The results of adrenalectomy in advanced breast cancer in 500 consecutive patients. Surg Gynecol Obstet 125: 747, 1967. 6. Moore FD, Van Devanter SB, Boyden CM, Lokich J, Wilson RD: Adrenalectomy with chemotherapy in the treatment of advanced breast cancer: objective and subjective resoonse rates; duration and quality-of life. Surgej76: 376, i974. 7. Dao TL, Nemoto T, Bross I: A controlled randomized comoarative study of early and late adrenalectomy in women with advanced breast cancer, p 177. Prognostic Factors in Breast Cancer. Forrest APM, Kunkler PB, ed. Edinburgh and London, E. & S. Livingstone Ltd. 1968.
The American Journal of Surgery
Metastatic
8. Fracchia AA, Farrow JH, Miller TR, Tollefesen HR. Greenberg, EJ, Knapper WH: Hypophysectorny as compared with adrenalectomy in the treatment of advanced carcinoma of the breast. Surg Gynecot Obstet 133: 241, 1971. 9. Leaper DJ: A clinical index for selection of breast cancer patients for adrenalectomy. Br J Surg 63: 759, 1976. 10. Brown PW, Terg JJ, King R, Lawrence J: Bilateral adrenalectomy for metastatic breast cancer. Arch Sorg 110: 77, 1975. 11. Silverstein MJ, Byron RL, Yonemoto RH, Riihimaki DU, Schuster
Volume137,
May
1979
Breast
Cancer
G: Bilateral adrenalectomy for advanced breast cancer: a 21 year experience. Surgery 77: 825, 1975. 12. Jensen EV, Smith S, De Sombre ER: Hormone dependency in breast cancer, p 131. Progress in Clinical and Biological Research, vol. 12. Breast Cancer (Montague ACW, Stonesifer GL, Lewison EF, ed). New York, Alan R. Liss Inc., 1977. 13. McGuire WL, Horowitz KB, Pearson DH, Segaloff A: Current status of estrogen and progesterone receptors in breast cancer. Cancer 39: 2934, 1977.
633