T H E ROLE OF EXTIRPATIVE PROCEDURES I N CANCER OF THE BREAST

IAN MACDONALD, M.D.

HE clinician’s priniary problem when con- T sidering a woman with disseminated mam- mary cancer is the choice and timing of abla- tive procedures, granted there is some evidence at hand as to their value. This would seem to be so from the evidence presented at this sym- posium. At the present time our own program of attempting to select ablative procedures and the choice of such procedures is as follows.

In premenopausal women an oophorectomy is performed as the primary attack on dissemi- nated disease, or disease beyond the phase of local recurrence or unifocal skeletal deposits and other limited mani€estations of incur- ability. In postmenopausal women-those who are postmenopausal by five or more years after a natural menopause or six or more months after artificial induction of the menopause- our test for eligibility for adrenalectomy at present is the use of estrogenic hormones.

In either event, if the disease is responsive to either oophorectomy in the premenopausal woman or estrogens in the postmenopausal one, we then consider her as a favorable can- didate for adrenalectomy. The objective re- gression that we like to see prior to considering adrenalectomy is objective regression for not less than six months after either of these pro- cedures.

This approach is based on our belief that successive attempts to alter steroid metabolism will, in responsive neoplasms, achieve repeated remissions, and that the sum of these remis- sions will exceed in duration those produced either by oophorectomy and adrenalectomy combined or by a primary hypophysectomy. I t is, if you will, a therapeutic guerrilla warfare or a sort of rear-guard action against the neo- plasm, as compared with the surgical block- buster type of extirpative procedure.

Our results with oophorectomy in premeno- pausal women are remarkably similar to those

From the University of Southern California School of Medicine, Los Angeles, California.

Presented at the Annual Scientific Session of the American Cancer Society, Inc., New York, New York, October 30, 1956.

Received for publication January 7, 1957.

TABLE 1

SION AFTER ADRENALECTOMY IN INCIDENCE OF METASTASIS AND REGRES-

FORTY-SIX PATIENTS

Site Incidence Regression ’

Bone 39 17 Lungs and pleura 14 7 Skin and subcutaneous tissues 19 11 Area producing edema of arm 8 2 Lymph nodes 17 1 (’ Intracranial 5 2 Liver 3 1

reported by Pearson (pp. 799-804). Approxi- mately four out of ten premenopausal women had objective regression of disease by oophorec- tomy alone. In our series, the duration of this remission has averaged nine and a half months.

Of sixty-nine patients who were postmeno- pausal, by the definition offered previously, and who responded to estrogen therapy, twelve obtained regression of disease for less than six months; thirtythree, for six to twelve months: cighteen, for twelve to twenty-four months; and six, for more than twenty-four months. The average duration of regression €or estrogen- treated patients was sixteen months. Our ex- perience in forty-six carefully selected cases is represented by the incidence of metastasis to various sites and the regressions obtained by adrenalectomy shown in Table 1.

-4s has been reported by others, there are certain areas of metastatic deposits, such as skin and subcutaneous tissues, in which the percentage of regression is striking. In skeletal, pulmonary, and pleural metastasis the results are less gratifying. Regression of cerebral and hepatic metastasis is rare.

Following the criteria that I have described for estrogen therapy in postmenopausal women, I have reviewed eighteen cases of ad- renalectomy done in the past two years for patients with estrogen-responsive neoplasms. This is a selected group, obtained by applying the criteria that the patient be less than 60 years of age and that she be without evidence of cerebral metastasis, but with genuine dis- seminated peripheral, soft-tissue, skeletal, or pulmonary metastasis, or combinations of two

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806 CANCER July-August 1957 Vol. 10

or more of these types. Out of eighteen patients there were six in whom progression of disease occurred aiter adrenalectoniy and twelve in whom regression occurred. In this highly se- lected group, then, there were two out of three women in whom there was very satisfactory control of disease aiter adrenalectomy. Of these eighteen patients, the six in whom the disease was progressive all survived less than six months; two patients survived six to twelve months and €our survived twelve to twenty-four months. At the present time there are six who are curviving more than two years. The aver- age longevity in these eighteen patients is fifteen months, compared with an average longevity of only eight months in the series of forty-six cases in which no such criteria were used.

T submit, then, on a theoretical basis, at least, and 1 grant that I cannot prove it at the pres- ent time, that one inay achieve a cumulative longevity by this fractional attempt to alter steroid metabolism; that responsive women who have oophorectomy prior to menopause will have nine and one half months’ palliation with oophorectomy and fifteen months’ pallia- tion with adrenalectomy, for a total ol twenty- four and a half months; that postmenopausal women will have in responsive cases sixteen month5’ control of disease with estrogens and fifteen months’ further duration of lire with adrenalectomy, for a total of thirty-one rnon ths.

This is an exercise in speculative mathe- matics, but our experience to date indicates that we will have to be convinced that this argument for fractional alterations of steroid metabolism is not valid. In this respect, I was interested in Cade’s report (pp. 777-788) that of women responsive to hormones, thirty of thirty-nine had regression after adrenalectomy, or approximately three out of four, while only one of two who did not respond to hormones had regrmsion after adrenalectomy.

We have no possible doubt that the phys- iological age of the woman is of importance in selecting patients for adrenalectomy. The €ew patients on whom we have operated who have been past the rather arbitrary chrono- logical line ol 60 years of age have all done badly. t V e have also seen a few patients in whom very prompt augmentation of disease by administered steroid hormones was so striking that we proceeded with adrenalectomy. In about half of this small group there has been sa tisbctory regression after adrenalectomy.

I have 110 experience with hypophysectomy. I would suggest only that proof is still lacking that hypophysectomy does anything more than remove the adrenotropic factors. The percent- age of adrenalectomized women in whom there is regression of disezse and who then are sub- jected to hypophysectomy and obtain a sec- ond regression from this more ambitious ex- tirpative measure seeins to correspond with the pelLentage of patients who probably have accessory adrenal tissue. One may grant read- ily that the growth hormone or perhaps pro- lactin may be a factor, but one would also suggest that this is still to be proved. We there- fore believe that primary hypophysectomy is as yet an unwarranted measure.

The concept of estrogen-dependent mam- mary cancer, although it seems to be valid by some of the metabolic evidence presented by Pearson, seems to me to be something less than the real answer to the problem of hormone dependency. One would think that if the sit- uation of responsiveness or lack of responsive- ness to manipulation of steroid metabolism were a simple sort of affair, the most dramatic results would be obtained by administration of androgenic steroids to the premenopausal woman. On the contrary, attempts to admin- ister steroid hormone, in the form oE andro- gens, to this group have been most miserable in their effects. It would seem possible to specu- late that differences in tissue metabolism are probably a more likely explanation.

We have recently been interested, as a par- enthetic note, in using prednisone in doses of 100 mg. daily for a period of about three weeks as a possible means of selecting women who may respond to adrenalectomy. Our ex- perience in this is still far too limited to offer any observation, but of three patients for whom this has been done, the two who showed not only subjective but also early objective evidence of regression have so far had good regressions with adrenalectomy.

The problem, then, as we see it, is for the clinician to decide what ablative procedures will offer enough women control of their dis- ease to be worthwhile in relation to the sever- ity of the procedure. The answer, so far as oophorectomy is concerned, is rather easy. The amount of stress to the patient i5 niinimal and the benefits that can be achieved are so obvi- OIXS, both in the series reported by Trevesl and mentioned by Pearson, and in our own experience, that oophorectomy has an estab- lished place.

EXTIRPATIVE PROCEDURES IN BREAST CANCER - Macdunald 807 gression and some promise of duration of that regression for a p e r i d of one year O r m ~ e .

No. 4

The problem so far as adrenalectomy is con- cerned is in developing criteria for selection of these patients. Our belief is that we ought to be able to offer women whom we regard REFERENCE

- 1. TREVES, N.: Evaluation of prophylactic castration

in treatment of niammary carcinoma; analysis of 152 as candidates for adrenalectomy 'Ornethi%

close to a 50 per cent chance of objective re- patients. Cancer 10: 393-407, 1957.