- Email: [email protected]
Carcinoma of the breast
CARCINOMA PRESENT HOWARD
OF THE BREAST*
STATUS
OF THERAPY
JONES, JR.,
W.
M.D.
Baltimore, Maryland
I
T is a remarkable thing that for over a haIf century the radicaI operation for cancer of the breast has been a sine qua non for breast cancer theraDv. Attempts to improve the end resuIts’ Lf this disease have been in the form of adjuncts
19006 t-I I I I910 I I I Ii 1915 I ii
more deaths than cancer of any other site in women. In 1946, 302 individuaIs succumbed to this disease. This is approximateIy one-fourth of a11 femaIe deaths from cancer in this state. In the Iast twenty years the number of deaths has
1 I 1920 I 11 11 192 115 11 11 193011 11 1935 11
11 111 1940 111 1945 110
YEAR
FIG. I. Deaths and death rates (per ~oo,ooo female population) breast in MaryIand, Igo6 to 1946.
of femaIes from cancer of the
about doubIed. That other factors besides an increase in femaIe popuIation is in operation is indicated by the fact that the rate per IOO,OOO femaIes has steadiIy risen.’ (Fig. I.)
to its operative treatment, such as preand postoperative irradiation, prophyIactic and therapeutic castration and prophyIactic and therapeutic androgenic therapy. It is the purpose of this paper to review the present status of the treatment of carcinoma of the breast with speciaI reference to the various adjuncts. In MaryIand cancer of the breast causes
EARLY
by
DIAGNOSIS
OF CARCINOMA
OF BREAST
If improved resuIts are to be obtained present therapeutic methods, earIy
* From the Department of Surgery, Johns Hopkins University, BaItimore, Md. Delivered at the Annual Meeting of the Medical and Chirurgical Faculty of Maryland, April 27, 1948. 696
American
Journal
of Surgery
Jones-Carcinoma diagnosis and treatment are imperative. That some progress in this direction is being made is indicated by Harrington’s’ figures which show that in the interval from 1910 to 1914 only 32 per cent of a11 women had had symptoms less than six
of Breast
697
that the same organization, now called The American Cancer Society, sponsored detection centers in Maryland and eIsewhere. At these centers unsuspected breast cancer is searched for as a part of the routine examination.
TABLE I
I .ess Than 2 MO.
.I $8 iZhcS>)
Duration of Symptoms 41 (19’:;)
27 (12%)
consultation, months prior to medica whereas, from 1935 to 1939 this figure had risen to 56.4yper cent. That much work in the field of Iay education may yet be done is indicated by the fact that between the years 1932 to 1942 inclusive 0nIy 57 per cent of patients in the series of 221 ward cases from the Johns Hopkins Hospital herein reported sought treatment within six months of the onset of symptoms. The simiIarity of this figure to Harrington’s is remarkabIe. (TabIe I.) AIthough it is impossibIe to overemphasize the importance of earIy diagnosis and the Iay education directed thereto, it is equaIIy important to note that even a compIeteIy successfu1 campaign to this end is by no means the answer to the breast cancer probIem. Even in those individuaIs operated upon within two months of the onset of symptoms there is a very dehnite and perhaps irreducible five-year mortaIity. A sizabIe percentage of these individuaIs have axiIIary metastasis when first seen in spite of a short clinica history. It seems reasonabre to suppose that the cancer in the individua1 is of a particuIarIy mahgnant variety. (TabIe II.) As Iong ago as rgr3 The American Society for the ControI of Cancer sponsored an organized campaign for lay education and earIy diagnosis. Routine periodic examinations were advised but it was not unti1 the cIose of WorId War II June,
19-19
___~
1 95 (43%)
Nodes negative logically.
patho-
Nodes positive logically.
patho-
~
20
I
I h
~ i
6 i 26
I
I
~
I I
10
~ 2$
I
49
I
In MaryIand during the Iirst year of operation of such centers 1,373 women were examined and two individuaIs were found in whom it was possibIe to make a cIinica1 diagnosis of breast cancer. Furthermore, about twenty additional individuaIs had breast noduIes, the nature of which demanded 1,microscopic diagnosis. UnfortunateIy, fohow-up studies on these individuaIs are not compIete so it is impossibIe to report the exact number of breast cancers other than the two which couId be diagnosed by cIinica1 examination. Webster,3 reporting on 1,600 examinees in IIIinois, found ten unsuspected malignant growths of the breast. In this connection it is interesting to note that forty-one of 1,623 primary ward breast cancers reported by Haagensen4 were diagnosed by routine examinations of patients for other compIaints. This represented 6.6 per cent of the entire series. In contrast there is but a singIe patient among the 22 I cases reported in whom an unsuspected cancer was discovered during the course of a routine physical examination for another complaint.
Jones-Carcinoma
698 SUKGlCAL
TKEATMENT THE
OF
CARCINOMA
OF
BREAST
It was previousIy mentioned that the radical operation is a sine qua non for breast cancer therapy. That it is important to pause to re-emphasize this point is indiTABLE RELIABILITY
OF
CLINICAL
Nodes Not PaIpable (78 Cases)
III
EXAMINATION
OF
AXILLA
PaIpabIe Nodes (I43 Cases)
Nodes Positive PathoIogicaIIy
Nodes Negative PathoIogicaIIy
Nodes Positive PathoIogicaIIy
Nodes Negative Pat hoIogicaIIy
34 (44%)
44 (56%)
116 (81%)
27 (19%)
cated by the fact that within the Iast year at Ieast four patients presented themselves for treatment at the Tumor CIinic at the Johns Hopkins Hospital with massive Iocal recurrence foIIowing simpIe mastectomy in individuaIs in whom no contraindication of the radica1 operation couId be found to exist. Furthermore, one of the two patients with cancer of the breast found in Maryland Detection Centers Iast year was treated by simpIe mastectomy because, according to the report no axiIIary nodes were of the surgeon, paIpabIe. In some sections of the country the use of simpIe mastectomy proved so widespread that BransfieId and CastigIianoS presented a report on this subject before the American Radium Society in ClevesimpIe mastectomy Iand in 1941. That with or without suppIementary irradiation is not the best therapy for breast cancer is indicated by three cIinica1 observations : I. A definite rate of cure exists in patients with&axiIIary metastasis. In the present series of 22 I ward cases 141 had pathoIogicaIIy proven axiIIary metastasis. Of these, thirty-nine or 26 per cent are Iiving at the end of five years. If these patients had not had an axiIIary dissection,
of Breast a substantial number, if not all, would have been dead. 2. The status of the axilla cannot be determined by cIinica1 examination. In 143 patients with paIpabIe axiIIary nodes 19 per cent did not have cancer as determined by a microscopic examination. On the other hand, among seventy-eight patients without paIpabIe nodes, 44 per cent were found to be positive by microscopic examination. (TabIe III.) 3. It is unIikeIy that irradiation can contro1 breast cancer metastastic to axilIary nodes. Because of the difficulty in proving the presence of cancer microscopicaIIy before treatment, no satisfying study of this subject exists. However, onIy about 25 to 35 per cent of breast cancers”,’ can be sterilized in the breast by preoperative irradiation. Because of inferior blood suppIy to the axiIIa and the general resistance of metastatic cancer in Iymph nodes, it is reasonabIe to assume that the rate of sterilization is substantiaIIy Iower than in the breast itseIf. These three cIinica1 observations, 26 per cent rate of cure with axiIIary metastases, inaccuracy of cIinica1 examination of the axiIIa and inabiIity to cure axiIIary metastases with irradiation, indicate that simpIe mastectomy has no pIace in the treatment of operable breast cancer in individuaIs in whom there is no constitutiona1 contraindication to operation. Furthermore, the literature contains no series which wouId support simpIe operation. PREOPERATIVE
IRRADIATION
It is generally agreed that preoperative therapy has not added to the tota saIvage in operabIe breast cancer.‘jv7 For the most part it has been given up as a routine method of therapy. However, this is not to say that it is not a usefu1 adjunct in the rare case of borderIine operabiIity. Our own materia1 is not extensive enough for a statistica anaIysis on this point but the case reported herein emphasizes its usefulness in an occasiona case. American
Journal
of Surgery
Jones-Carcinoma CASE I. &I. S. aged fifty, was admitted to the Tumor Clinic of the Department of Surgery of The Johns Hopkins Hospital on October 9, 1940. There had been a Iump on the right breast of at least one year’s duration. Ulceration of the skin was noted two months prior to admission. (Fig. 2.) Physical examination reveaIed the right breast to he involved by a hard mass and an ulcerated lesion 4 cm. in diameter above and to the right of the nippIe. There Lvere no palpable axillary lymph nodes. She m-as seen byDr. Grant Ward who suggested preoperative irradiation. She received 2,400 r (air) of x-ray through an anterior porta and a simiIar amount through a posterior porta and 1,700o r to the axilIa, 1,900 r through a tangentiaI portal to the breast and 1,000 r directly to ulcerated Iesion 200 KV, 30 cm. S. T. D., Thoreaus filtration. Response from the x-ray therapy was v-cry satisfactory and on December 20, 1940, the radical operation m-as carried out. A pathologic examination proved the diagnosis of carcinoma of the breast lyith axillary metastasis. The patient was last seen on October 14, 1947, at which time there was no evidence of a recurrence.
It is well to emphasize that a case considered inoperable on first examination should not be committed irrevocably to irradiation as some patients, considered borderline or inoperabIe cases, can he successfully operated upon after proper s-ray therapy. POSTOPERATIVE
IRRADIATION
The literature is not unanimous in the evaIuation of postoperative prophylactic roentgen therapy. In an eIeven-year period beginning in 1932, 304 ward patients were admitted to the Johns Hopkins HospitaI. Of these, fifty-two or 17 per cent were inoperable and were treated by x-ray and, in some instances, simpIe mastectomy. Of 252 patients, 221 were the remaining followed up for five years or Ionger and form the basis for the statisticat evaIuation of postoperative roentgen therapy. (TabIe IV.) One hundred three patients received no x-ray therapy whiIe the remaining I 18 received at least 2,000 r (air) to an anterior .June,
I 040
of Breast
699
FIG. 2. M. S., October 9, 1940, treated with preoperative roentgenotherapy and radical mastectomy; living and we11 seven years Iater.
porta and 2,000 r to a posterior portal within four months of the radical operation. Factors: 200 K. V. 20 M. A. 15 cm. by 13 cm. portaIs, 30 cm. T. S. D. Thoreus 200 r per day on filtration; treatments alternate portals. TABLE OPERABILITY WARD
CASES,
JOHNS
OF
IV
CARCINOMA HOPKINS
OF
Totai
I932 I933 ‘934 ‘935 1936 ‘937 1938 1939 ‘940 ‘94’ 1942
‘9 36 30 3o 29 25 24 31 33 25
Inoperable of Simple l\iIastectomy
I
3O4
*Number thesis.
Determinate Primary Operable
Primary lperable
16 (2)*
:, 8 6 8 2
3 4 5 2
22
i
1932-1942 T
T
Year
BREAST
HOSPITAL
5
/
52
35 22 24 21 23 21 27 28 23 17
“4 2G
(5) (3) (5) (2) (1) (2) (5) (3) (2) irj
10 10 10 22 10 22 25 21 I6
252 (3Ij
22L I
of five-year
unfolIowed
cases in paren-
Table v shows the cases according to the pathoIogic findings in the axilla. It must be concIuded that no statistica difference exists between the group receiving roentgen therapy and the group treated only by operation. Furthermore, the survival time in cases in which patients succumbed within five years does not differ in the two groups. (Fig.
3.)
Jones-Carcinoma
7oo
The over-a11 five-year saIvage is 74 of or 34 per cent. In an institution in which radica1 operation has been standardized for over haIf a century, these findings may be of more than passing interest. 221
of Breast cancer and (2) as a prophyIactic measure at the time of radicaI mastectomy. To SchinzingeP beIongs the credit of suggesting oophorectomy in advanced cancer as a therapeutic method aIthough he
MONTHS
FIG. 3. Length
of Iife in carcinoma
TABLE FIVE-YEAR
Therapy
END
v RESULTS
Nodes Negative Pathologically
Nodes Positive PathoIogicaIIy
Living
Living
Dead
I3
‘9 (28%)
49
10
10 (24%)
63
23
$9 (26%)
112
Dead
Without postoperative x-ray. 22 (63 %) With postoperative x-ray. ,..........25(71%) TotaI..............
CASTRATION
47 (66%)
AS
of the breast with pathoIogicaIIy
AN
ADJUNCT
TO
THERAPY
Castration has been advised for the treatment of breast cancer under two circumstances: (I) as a therapeutic method in inoperabIe
or recurrent
and
metastatic
positive
axiIIary nodes.
apparentIy made no report subsequent his suggestion at the SurgicaI Congress Germany in 1889.
to in
Beatsong pubIished the first actua1 case report of a singIe patient with improvement. Since then a series of papers on the subject has appeared, especiaIIy during the era prior to the genera1 use of x-ray therapy but continuing sporadicaIIy to the present time so that case reports now number severa hundred. The most remarkabIe aspect of this subject is the aImost compIete unanimity in reporting up to 30 per cent definite but temporary satisfactory end resuIts Bone metastases are most favorabIy affected and recaIc&cation has been observed. ReIief of pain without roentgenographic evidence of change has also been observed. The simiIarity of these American
Journal
of Surgery
Jones-Carcinoma cases to those receiving androgenic therapy is striking.x~“‘-‘g If irradiation is used against a local lesion in addition to castration, the effect is more difficult to evaIuate and is overshadowed by the Iocal radioIogic response. Thus AhlbomZo treated the metastatic areas with x-ray and, in addition, insisted on roentgen castration. By this method in 163 cases it was impossible statisticaIIy to demonstrate any increase in the Iength of life of the castrate group. The rationale of prophyIactic castration at the time of radicaI operation presupposes the desirability of ehminating a11 possibIe estrogen from the organism. It shouId be pointed out, however, that oophorectomy by no means insures the complete absence of estrogen. Zundek and von Eu1er,21 Robson et aI., Frank23 and Laroche et aI.2” demonstrated up to 200 mouse units of estrogen per L. of urine in menopausal and compIeteIy castrate women. Be this as it may, the absence of ovarian function seems to be associated with a decreased incidence of breast cancer and a lesser likelihood of recurrence a1though there is not unanimity of opinion. HerreIIz5 reviewed the records of 1,906 women treated for breast cancer and I,OI I women of similar age group as contro1s. In the cancer group the evidence of complete oophorectomy before the treatment of cancer was 1.5 per cent. On the other hand, the incidence of biIatera1 oophorectomy in the controI group was 13.4 per cent or ten times as great. Furthermore, OIch 26 found that in a series of 342 women approximate1y fifty y,ears of age with cancer of the breast, five times as many had a deIayed menopause as compared with a series of non-cancerous women. TayIoP made a pre1iminary report in I 939 on forty-seven prophyIactic castrations in young women. His genera1 conclusion was that 2.7 years after operation there were no more survivors than wou1d be expected in their material. Taylor comJune,
1949
“01
of Breast
pleteIy gave up the use of prophylactic castration foIIowing his earlier report.2s On the other hand, HorsIeyzg is of the opinion that oophorectomy improved his results. In twenty-six cases twenty patients or 77 per cent were Iiving and we11 three years postoperativeIy compared to 46 per cent without castration in his cIinic. HorsIey has recentIy stated that twentyseven cases have now been done five years ago or more. Of these there have been six deaths from recurrence. There has been one death from a cause other than recurrence, this patient Iiving five years after operation. An autopsy showed no evidence Twenty patients are of any recurrence. living, one of whom has a metastasis in the supracIavicuIar area. This wou1d be 73 per cent who have gone five years or more without any evidence of recurrence.“O From these scanty and contradictory reports it seems that further series so treated wouId be of tremendous importance. ANDROGENS OF
AS
AN
CANCER
ADJUNCT OF
THE
TO TREATMENT BREAST
Androgens in the form of testosterone proprionate has been used (I ) therapeuticaIIy in advanced or recurrent cases and (2) prophyIacticaIIy beginning at the time of radica1 breast operation. The author has recentIy reviewed his experience with this agent on advanced breast cancer. 31 Further experience has served onIy to confirm the opinions previousIy expressed. In soft tissue involvement, such as chest waI1, opposite breast, liver, Iung, etc., the results in a smaI1 percentage of cases may be very gratifying for varying periods of time but probably several months at the most. In the greatest percentage of cases, however, no effect can be noted on the progression of the disease. With metastatic bone disease no effect may be noted or the patient might have striking pain reIief with recaMication of the Iesion or the anomalous circumstance of cIinica1 improvement but no roentgenographic change or even roentgenographic progression may take pIace. As with
Jones-Carcinoma
702
soft tissue involvement, any improvement either cIinica1 or actuaI is Iimited in time. The usua1 dosage is IOO mg. three times weekly although a satisfactory response may sometimes be obtained with Iess. It is our beIief that if one obtains a favorabIe response, the treatment should be continued indefiniteIy. The occasiona briIIiant response to testosterone has Ied to its rather widespread use as the primary agent in treating metastatic inoperabIe breast cancer. In view of the variability of response and the generaIIy satisfactory benefit from roentgen therapy it is we11 to emphasize that in we11 IocaIized Iesions, either soft tissue or bone, roentgen therapy is stiI1 the best therapeutic agent. On the other hand, in roentgen faiIure and in generaIized disease testosterone may produce an occasiona astounding result. The first and most ardent advocate of prophyIactic testosterone was Prudente.32 He treated his first patient in ApriI, 1939. His resu1t.s after three, four and five years indicate an increase of IOO per cent compared with end resuIts of previous years. A later communication33 substantiated his earIier impression. The dosage of testosterone varied in Prudente’s series from 23 to 173 mg. per week. PREGNANCY
FOLLOWING
RADICAL
BREAST
OPERATION
It is generaIIy agreed that pregnancy acceIerates the growth of carcinoma aIready present. Westberg, however, on the basis of experience in Sweden has presented a contrary point of view. Be this as it may, pregnancy subsequent to radica1 breast operation might Iight up otherwise Iatent metastases. The foIIowing three case reports wiI1 iIIustrate this possibiIity. CASE I. M. B., No. 72,736, aged forty, had had a Ieft radicaI breast operation in January, 1936. The patient was first seen in the OutPatient Department at Johns Hopkins HOSpita1 on November 4, 1936. FoIIowing the radicaI operation she did we11 until two months
of Breast prior to her admission to the hospita1 when she observed a considerabIe sweIIing of her arm and hand. An examination showed extensive local recurrence in the chest wall and the axiIIa. She was aIso thought to have pIura1 effusion from metastasis. The uterus was enIarged to the size of tweIve weeks’ pregnancy. In spite of a therapeutic abortion on November death was prompt. Recurrence 11, 1936, appearing at the onset of pregnancy and the viruIent and short clinica course are suggestive of a causa1 reIationship.
CASE II. M. G. No. 73,430, aged thirtynine, had a radica1 breast operation on September 22, 1936. PathoIoglc examination showed meduIIary carcinoma without metastasis to the axiIIa. About January IS, 1937, she had severe pain in the back and in the right Ieg. She Iost considerabIe weight and did not menstruate from the time of her discharge in 1936. She was readmitted to Johns Hopkins Hospital on February 2, 1937 foIlowing a spontaneous abortion at home. She died very soon thereafter with generaIized cancinomatoses. CASE II. H. G., No. 270,786, aged twentynine, had a right radica1 mastectomy performed by Dr. BIaIock on September I, 1942. PathoIogic examination reveaIed comedo carcinoma with regional metastases. The patient was seen on ApriI 4, 1944, for a routine check-up. There was no evidence of metastases or IocaI recurrence. However, she was found to be six months’ pregnant. The baby was deIivered uneventfuIIy. By August 1st there was a cough and chest pain. X-ray revealed many metastatic Iesions in the ribs. She died on October 18,
1944. Trout35 reported two cases of pregnancy occurring four and six years, respectivery, after radical mastectomy. In each instance, simuItaneousIy with the pregnancy, carcinoma occurred in the opposite ‘breast. Trout circuIarized severa of his surgica1 friends and coIIected seventeen cases of pregnancy subsequent to radical mastectomy. In thirteen of these carcinoma deveIoped in the opposite breast. Broemis36.37 reported substantiaIIy simiIar resuIts although Westberg reported severa instances of pregnancy subsequent to breast surgery without untoward effect. It is our belief, therefore, that pregnancy American
Journal
of Surgery
Jones-Carcinoma subsequent to radical breast operation exposes the patient to an unnecessary risk. It is indeed an additional argument for the routine use of castration at the time of radicaI operation in women in the childbearing age. At the very Ieast, the surgeon may be expected to assume the responsibility of advising his patients against pregnancy folIowing radicaI breast surgery. PRESENT
STATUS
OF
THERAPY
FOR
BREAST
CANCER
On the basis of the aforementioned review- it is suggested that the average individual with cancer of the breast shouId be subjected to immediate radica1 operation without preliminary irradiation. In inoperabIe cases or those of borderhne operability irradiation, sometimes alone or combined with surgery, has much to offer incIuding the possibiIity of a five-year cure. On the basis of experience it is not possible to demonstrate any improvement in five-year end resuIts from the routine use of postoperative prophylactic therapy. From theoretic considerations and from a review of the Iiterature, there is reason to believe that routine prophyIactic castrations, particuIarly in the chiId-bearing age, is to be seriously considered in the routine treatment of breast cancer. Furthermore, this procedure prevents pregnancv which, in some instances at least, is associated with widespread metastasis following radica1 breast surgery. Androgens play an important part in otherwise hopeless breast cancer but at the present time they are to be recommended only in those cases not suitable for high voltage, roentgen therapy or in cases of roentgen faiIure. KEFERENCES I. bIaryIand
State Department of Health. Bureau of Vita1 Statistics. Persona1 communication. 2. HARRINGTON, S. W. SurgicaI rates of radical mastectomy for uniIateraI and biIatera1 carcinoma of the breast. Surgery, 19: 154, 1946. 3. WEBSTER, H., PHII.LIPS, W. H., NODELIIO~FER,L., OLIVER, M. and PARSONS, E. Examination of the breasts and pelvic organs in apparentIy weI1 women. Illinois M. J., 89: 239, 1946.
of Breast
703
4. HAAGENSEN,C. D. and STOUT, A. P. C;Ircinom:r of the breast. Ann. Surg., I 10: 801, 1942. 5. BRAUSFIELD, J. W. and CASTIGLIANO, S. G. The inadequacy of simple mastectomy for inoperable cancer of the breast. Am. J. Roentpenol., 47: 748, 1942. 6. ADAIR, FRAF;K E. The effect of preoperative irradiation in primary operable cancer of the breast. Am. J. Roentgenol., 35: 359, ,936. 7. COHN, L. C. Carcinoma of the female breast. Arch. SW+,
44: 715,
194.2.
8. I~ALBERSTAEDTER,L. and HocH~~A~, II. The artificial menopause and cancer of the breast. J. A.M. A., 131: 810, 1946. g. BEATSON, G. T. On the treatment of inoperable cases of the mammaI: suggestions for a new method of treatment, with iIIustrative cases. Lancet, 2: ro4, 1896. to. THOMPSON, A. Analysis of cases in which oophorectomy was performed for inoperative carcinoma of the breast. &it. A4. J., 2: 1538, 1902. LI. LETT, H. AnaIysis of gg cases of inoperable carcinoma of breast treated by oophorectomy. Lancet, I: 227, 1905. 12. BEATSON, G. T. Treatment of inopcrablc carcinoma of female mammaI. Glasgotu M. J., 76: 8r, 1911. 13. DRESSER, RICHARD. Effect of ovarian irradiation as bone metastases of cancer of breast. Am. J. Roentgenok 35: 384, 1926. 14. HOFFMAK, W. J. Spontaneous Disappearance of metastatic nodules from carcinoma of breast foIIowing irradiation of ovaries. S. Clin. North America, 13: 494-498, 1933. 15. SMITH, E. G. SteriIization in carcinoma of breast. Am. J. Roentgenol., 36: 65, 1936. 16. \VITHERSPOON, J. T. Roentgen irradiation of ovaries as suppIement to surgical and radium therapy for mammary cancer. Arch. Sure., 33: 554. 1936. 17. RITVO, M. and PETERSON, 0. S., JR. Regression of bone metastases after ovarian steriIization. Am. J. Roentgenol., 5 I : 220, 1944. 18. TREVES, N., ABELS, J. C., WOO~ARD, H. Q. and FARROW, J. H. Effects of orchiectomy on primary and metastatic carcinoma. Surg., 6)nec. (*+ Obst., 79: 589, 1944. 19. ADAIR, F. E., TREVES, NORMAN, FARROU., .I. tI. and SCHARNAGEL, I. M. CIinicaI eIfccts of surgica1 and x-ray castration in mammary cancer. J. A. M. A., 128: 161, 1945. 20. AHLBO~~, H. Castration by rorntgen rays as auxilliary treatment in radiotherapy of cancer mammae at radium Iemmet. Acts Radical I I: 614-633, 1930. 21. ZONDEK, B. and VON E\:IxR, N. Follikuiinausscheidung im Harn des Kindes, der Frau und des Mannes. Skand. Arch. F. Plysiol. 67: 259, ‘934. 22. ROBSON, J. M., MACGRCGOR, T. N., ILLIUCIWOHTH, R. E. and STEERE, N. Urinary excretion of estrogen administered under experimentat conditions and after the menopause. Brit. hl. J., 1: 888, 1934. 23. FRAIUK, R. T. TOLDRER~ER, M. A. and SPIBL~IA~;.
704
Jones-Carcinoma F.
Present
endocrine
diagnosis
J. A. M. A., 103: 393, 1934.
and
therapy.
24. LAKOCHE, G., SIMMONNET, H. and HVLT, J. A. Contribution a L’etude des Variations du Taut de la Folliculine Chrr la Femme. Compt. rend. Sot. de biol., I 13: 286, 1933. 25. HERRELL, W. E. ReIative incidence of oophorectomy in women with and without carcinoma of breast. Am. J. Cancer, 29: 65, 1937. 26. OLCH, I. V. Menopausal age in women with cancer of the breast. Am. J. Cancer, 30: 563-566, 1937. 27. TAYLOR, G. W. Evaluation of ovarian sterilization for breast cancer. .%rg., @net. @YObst., 68: 452, ‘939. 28. TAYLOR, G. W. Persona1 communication, 1948. 29. HORSELY, Gtiu W. Treatment of cancer of the breast in pre-menopausal patients with radical amduthtion and bilateral oophorectomy. Am. J.
Surg., 125: 203, 1947. 30. HORSLEY, GUY W. Personal communication,
1948.
of Breast 31. JONES, I&WARD
W., JR. Testosterone in the treatment of advanced breast cancer. South M. J.,
4,: 4 1948.
12. PRUDENTE. A. Post-ooerative ProuhvIaxis of Rccurrent Mammary Cancer with Testosterone Propionate. Surg., Gynec. 0 Obst., 80: 575, 1945. 33. PRUDENTE, A. Personal communication, 1947. 34. WESTBERG, S. V. Prognosis of Breast Cancer for Pregnant and Nursing Women. Stockholm, 1946. Hakan, Ohlssons, Boktryckeri. 35. TROUT, H. H. The remaining breast after radical removal of the opposite side for carcinoma. Surg., Gynec. to Obst., 34: 630, 1922. 36. BROMEIS, H. Der Einffuss Schwangerschaft und der StiIIperiode auf den Brustkrebs und die Richlelinien des ArzIichen HandeIns. Deutscbe Ztscbr. f. Cbir., 252: 294, 1939. 37. BROMEIS, H. Zur Frage einer neuen Schwangerschaft nach RadikaI operation eines Brustkrebs. 1
&
”
Cbirurg., I I : 662, 1939.
SOLITARY, uniIatera1 cysts in women undergoing menopause that show recent increase in size are often malignant. PavIovsky et al. recently studied I I I cases of cancer of the breast and found that in I I per cent of them there was an associated condition of chronic cystic mastitis. (Richard
A. Leonardo,
M.D.)
American
Journal
of
Surgery
OF THE BREAST*
STATUS
OF THERAPY
JONES, JR.,
W.
M.D.
Baltimore, Maryland
I
T is a remarkable thing that for over a haIf century the radicaI operation for cancer of the breast has been a sine qua non for breast cancer theraDv. Attempts to improve the end resuIts’ Lf this disease have been in the form of adjuncts
19006 t-I I I I910 I I I Ii 1915 I ii
more deaths than cancer of any other site in women. In 1946, 302 individuaIs succumbed to this disease. This is approximateIy one-fourth of a11 femaIe deaths from cancer in this state. In the Iast twenty years the number of deaths has
1 I 1920 I 11 11 192 115 11 11 193011 11 1935 11
11 111 1940 111 1945 110
YEAR
FIG. I. Deaths and death rates (per ~oo,ooo female population) breast in MaryIand, Igo6 to 1946.
of femaIes from cancer of the
about doubIed. That other factors besides an increase in femaIe popuIation is in operation is indicated by the fact that the rate per IOO,OOO femaIes has steadiIy risen.’ (Fig. I.)
to its operative treatment, such as preand postoperative irradiation, prophyIactic and therapeutic castration and prophyIactic and therapeutic androgenic therapy. It is the purpose of this paper to review the present status of the treatment of carcinoma of the breast with speciaI reference to the various adjuncts. In MaryIand cancer of the breast causes
EARLY
by
DIAGNOSIS
OF CARCINOMA
OF BREAST
If improved resuIts are to be obtained present therapeutic methods, earIy
* From the Department of Surgery, Johns Hopkins University, BaItimore, Md. Delivered at the Annual Meeting of the Medical and Chirurgical Faculty of Maryland, April 27, 1948. 696
American
Journal
of Surgery
Jones-Carcinoma diagnosis and treatment are imperative. That some progress in this direction is being made is indicated by Harrington’s’ figures which show that in the interval from 1910 to 1914 only 32 per cent of a11 women had had symptoms less than six
of Breast
697
that the same organization, now called The American Cancer Society, sponsored detection centers in Maryland and eIsewhere. At these centers unsuspected breast cancer is searched for as a part of the routine examination.
TABLE I
I .ess Than 2 MO.
.I $8 iZhcS>)
Duration of Symptoms 41 (19’:;)
27 (12%)
consultation, months prior to medica whereas, from 1935 to 1939 this figure had risen to 56.4yper cent. That much work in the field of Iay education may yet be done is indicated by the fact that between the years 1932 to 1942 inclusive 0nIy 57 per cent of patients in the series of 221 ward cases from the Johns Hopkins Hospital herein reported sought treatment within six months of the onset of symptoms. The simiIarity of this figure to Harrington’s is remarkabIe. (TabIe I.) AIthough it is impossibIe to overemphasize the importance of earIy diagnosis and the Iay education directed thereto, it is equaIIy important to note that even a compIeteIy successfu1 campaign to this end is by no means the answer to the breast cancer probIem. Even in those individuaIs operated upon within two months of the onset of symptoms there is a very dehnite and perhaps irreducible five-year mortaIity. A sizabIe percentage of these individuaIs have axiIIary metastasis when first seen in spite of a short clinica history. It seems reasonabre to suppose that the cancer in the individua1 is of a particuIarIy mahgnant variety. (TabIe II.) As Iong ago as rgr3 The American Society for the ControI of Cancer sponsored an organized campaign for lay education and earIy diagnosis. Routine periodic examinations were advised but it was not unti1 the cIose of WorId War II June,
19-19
___~
1 95 (43%)
Nodes negative logically.
patho-
Nodes positive logically.
patho-
~
20
I
I h
~ i
6 i 26
I
I
~
I I
10
~ 2$
I
49
I
In MaryIand during the Iirst year of operation of such centers 1,373 women were examined and two individuaIs were found in whom it was possibIe to make a cIinica1 diagnosis of breast cancer. Furthermore, about twenty additional individuaIs had breast noduIes, the nature of which demanded 1,microscopic diagnosis. UnfortunateIy, fohow-up studies on these individuaIs are not compIete so it is impossibIe to report the exact number of breast cancers other than the two which couId be diagnosed by cIinica1 examination. Webster,3 reporting on 1,600 examinees in IIIinois, found ten unsuspected malignant growths of the breast. In this connection it is interesting to note that forty-one of 1,623 primary ward breast cancers reported by Haagensen4 were diagnosed by routine examinations of patients for other compIaints. This represented 6.6 per cent of the entire series. In contrast there is but a singIe patient among the 22 I cases reported in whom an unsuspected cancer was discovered during the course of a routine physical examination for another complaint.
Jones-Carcinoma
698 SUKGlCAL
TKEATMENT THE
OF
CARCINOMA
OF
BREAST
It was previousIy mentioned that the radical operation is a sine qua non for breast cancer therapy. That it is important to pause to re-emphasize this point is indiTABLE RELIABILITY
OF
CLINICAL
Nodes Not PaIpable (78 Cases)
III
EXAMINATION
OF
AXILLA
PaIpabIe Nodes (I43 Cases)
Nodes Positive PathoIogicaIIy
Nodes Negative PathoIogicaIIy
Nodes Positive PathoIogicaIIy
Nodes Negative Pat hoIogicaIIy
34 (44%)
44 (56%)
116 (81%)
27 (19%)
cated by the fact that within the Iast year at Ieast four patients presented themselves for treatment at the Tumor CIinic at the Johns Hopkins Hospital with massive Iocal recurrence foIIowing simpIe mastectomy in individuaIs in whom no contraindication of the radica1 operation couId be found to exist. Furthermore, one of the two patients with cancer of the breast found in Maryland Detection Centers Iast year was treated by simpIe mastectomy because, according to the report no axiIIary nodes were of the surgeon, paIpabIe. In some sections of the country the use of simpIe mastectomy proved so widespread that BransfieId and CastigIianoS presented a report on this subject before the American Radium Society in ClevesimpIe mastectomy Iand in 1941. That with or without suppIementary irradiation is not the best therapy for breast cancer is indicated by three cIinica1 observations : I. A definite rate of cure exists in patients with&axiIIary metastasis. In the present series of 22 I ward cases 141 had pathoIogicaIIy proven axiIIary metastasis. Of these, thirty-nine or 26 per cent are Iiving at the end of five years. If these patients had not had an axiIIary dissection,
of Breast a substantial number, if not all, would have been dead. 2. The status of the axilla cannot be determined by cIinica1 examination. In 143 patients with paIpabIe axiIIary nodes 19 per cent did not have cancer as determined by a microscopic examination. On the other hand, among seventy-eight patients without paIpabIe nodes, 44 per cent were found to be positive by microscopic examination. (TabIe III.) 3. It is unIikeIy that irradiation can contro1 breast cancer metastastic to axilIary nodes. Because of the difficulty in proving the presence of cancer microscopicaIIy before treatment, no satisfying study of this subject exists. However, onIy about 25 to 35 per cent of breast cancers”,’ can be sterilized in the breast by preoperative irradiation. Because of inferior blood suppIy to the axiIIa and the general resistance of metastatic cancer in Iymph nodes, it is reasonabIe to assume that the rate of sterilization is substantiaIIy Iower than in the breast itseIf. These three cIinica1 observations, 26 per cent rate of cure with axiIIary metastases, inaccuracy of cIinica1 examination of the axiIIa and inabiIity to cure axiIIary metastases with irradiation, indicate that simpIe mastectomy has no pIace in the treatment of operable breast cancer in individuaIs in whom there is no constitutiona1 contraindication to operation. Furthermore, the literature contains no series which wouId support simpIe operation. PREOPERATIVE
IRRADIATION
It is generally agreed that preoperative therapy has not added to the tota saIvage in operabIe breast cancer.‘jv7 For the most part it has been given up as a routine method of therapy. However, this is not to say that it is not a usefu1 adjunct in the rare case of borderIine operabiIity. Our own materia1 is not extensive enough for a statistica anaIysis on this point but the case reported herein emphasizes its usefulness in an occasiona case. American
Journal
of Surgery
Jones-Carcinoma CASE I. &I. S. aged fifty, was admitted to the Tumor Clinic of the Department of Surgery of The Johns Hopkins Hospital on October 9, 1940. There had been a Iump on the right breast of at least one year’s duration. Ulceration of the skin was noted two months prior to admission. (Fig. 2.) Physical examination reveaIed the right breast to he involved by a hard mass and an ulcerated lesion 4 cm. in diameter above and to the right of the nippIe. There Lvere no palpable axillary lymph nodes. She m-as seen byDr. Grant Ward who suggested preoperative irradiation. She received 2,400 r (air) of x-ray through an anterior porta and a simiIar amount through a posterior porta and 1,700o r to the axilIa, 1,900 r through a tangentiaI portal to the breast and 1,000 r directly to ulcerated Iesion 200 KV, 30 cm. S. T. D., Thoreaus filtration. Response from the x-ray therapy was v-cry satisfactory and on December 20, 1940, the radical operation m-as carried out. A pathologic examination proved the diagnosis of carcinoma of the breast lyith axillary metastasis. The patient was last seen on October 14, 1947, at which time there was no evidence of a recurrence.
It is well to emphasize that a case considered inoperable on first examination should not be committed irrevocably to irradiation as some patients, considered borderline or inoperabIe cases, can he successfully operated upon after proper s-ray therapy. POSTOPERATIVE
IRRADIATION
The literature is not unanimous in the evaIuation of postoperative prophylactic roentgen therapy. In an eIeven-year period beginning in 1932, 304 ward patients were admitted to the Johns Hopkins HospitaI. Of these, fifty-two or 17 per cent were inoperable and were treated by x-ray and, in some instances, simpIe mastectomy. Of 252 patients, 221 were the remaining followed up for five years or Ionger and form the basis for the statisticat evaIuation of postoperative roentgen therapy. (TabIe IV.) One hundred three patients received no x-ray therapy whiIe the remaining I 18 received at least 2,000 r (air) to an anterior .June,
I 040
of Breast
699
FIG. 2. M. S., October 9, 1940, treated with preoperative roentgenotherapy and radical mastectomy; living and we11 seven years Iater.
porta and 2,000 r to a posterior portal within four months of the radical operation. Factors: 200 K. V. 20 M. A. 15 cm. by 13 cm. portaIs, 30 cm. T. S. D. Thoreus 200 r per day on filtration; treatments alternate portals. TABLE OPERABILITY WARD
CASES,
JOHNS
OF
IV
CARCINOMA HOPKINS
OF
Totai
I932 I933 ‘934 ‘935 1936 ‘937 1938 1939 ‘940 ‘94’ 1942
‘9 36 30 3o 29 25 24 31 33 25
Inoperable of Simple l\iIastectomy
I
3O4
*Number thesis.
Determinate Primary Operable
Primary lperable
16 (2)*
:, 8 6 8 2
3 4 5 2
22
i
1932-1942 T
T
Year
BREAST
HOSPITAL
5
/
52
35 22 24 21 23 21 27 28 23 17
“4 2G
(5) (3) (5) (2) (1) (2) (5) (3) (2) irj
10 10 10 22 10 22 25 21 I6
252 (3Ij
22L I
of five-year
unfolIowed
cases in paren-
Table v shows the cases according to the pathoIogic findings in the axilla. It must be concIuded that no statistica difference exists between the group receiving roentgen therapy and the group treated only by operation. Furthermore, the survival time in cases in which patients succumbed within five years does not differ in the two groups. (Fig.
3.)
Jones-Carcinoma
7oo
The over-a11 five-year saIvage is 74 of or 34 per cent. In an institution in which radica1 operation has been standardized for over haIf a century, these findings may be of more than passing interest. 221
of Breast cancer and (2) as a prophyIactic measure at the time of radicaI mastectomy. To SchinzingeP beIongs the credit of suggesting oophorectomy in advanced cancer as a therapeutic method aIthough he
MONTHS
FIG. 3. Length
of Iife in carcinoma
TABLE FIVE-YEAR
Therapy
END
v RESULTS
Nodes Negative Pathologically
Nodes Positive PathoIogicaIIy
Living
Living
Dead
I3
‘9 (28%)
49
10
10 (24%)
63
23
$9 (26%)
112
Dead
Without postoperative x-ray. 22 (63 %) With postoperative x-ray. ,..........25(71%) TotaI..............
CASTRATION
47 (66%)
AS
of the breast with pathoIogicaIIy
AN
ADJUNCT
TO
THERAPY
Castration has been advised for the treatment of breast cancer under two circumstances: (I) as a therapeutic method in inoperabIe
or recurrent
and
metastatic
positive
axiIIary nodes.
apparentIy made no report subsequent his suggestion at the SurgicaI Congress Germany in 1889.
to in
Beatsong pubIished the first actua1 case report of a singIe patient with improvement. Since then a series of papers on the subject has appeared, especiaIIy during the era prior to the genera1 use of x-ray therapy but continuing sporadicaIIy to the present time so that case reports now number severa hundred. The most remarkabIe aspect of this subject is the aImost compIete unanimity in reporting up to 30 per cent definite but temporary satisfactory end resuIts Bone metastases are most favorabIy affected and recaIc&cation has been observed. ReIief of pain without roentgenographic evidence of change has also been observed. The simiIarity of these American
Journal
of Surgery
Jones-Carcinoma cases to those receiving androgenic therapy is striking.x~“‘-‘g If irradiation is used against a local lesion in addition to castration, the effect is more difficult to evaIuate and is overshadowed by the Iocal radioIogic response. Thus AhlbomZo treated the metastatic areas with x-ray and, in addition, insisted on roentgen castration. By this method in 163 cases it was impossible statisticaIIy to demonstrate any increase in the Iength of life of the castrate group. The rationale of prophyIactic castration at the time of radicaI operation presupposes the desirability of ehminating a11 possibIe estrogen from the organism. It shouId be pointed out, however, that oophorectomy by no means insures the complete absence of estrogen. Zundek and von Eu1er,21 Robson et aI., Frank23 and Laroche et aI.2” demonstrated up to 200 mouse units of estrogen per L. of urine in menopausal and compIeteIy castrate women. Be this as it may, the absence of ovarian function seems to be associated with a decreased incidence of breast cancer and a lesser likelihood of recurrence a1though there is not unanimity of opinion. HerreIIz5 reviewed the records of 1,906 women treated for breast cancer and I,OI I women of similar age group as contro1s. In the cancer group the evidence of complete oophorectomy before the treatment of cancer was 1.5 per cent. On the other hand, the incidence of biIatera1 oophorectomy in the controI group was 13.4 per cent or ten times as great. Furthermore, OIch 26 found that in a series of 342 women approximate1y fifty y,ears of age with cancer of the breast, five times as many had a deIayed menopause as compared with a series of non-cancerous women. TayIoP made a pre1iminary report in I 939 on forty-seven prophyIactic castrations in young women. His genera1 conclusion was that 2.7 years after operation there were no more survivors than wou1d be expected in their material. Taylor comJune,
1949
“01
of Breast
pleteIy gave up the use of prophylactic castration foIIowing his earlier report.2s On the other hand, HorsIeyzg is of the opinion that oophorectomy improved his results. In twenty-six cases twenty patients or 77 per cent were Iiving and we11 three years postoperativeIy compared to 46 per cent without castration in his cIinic. HorsIey has recentIy stated that twentyseven cases have now been done five years ago or more. Of these there have been six deaths from recurrence. There has been one death from a cause other than recurrence, this patient Iiving five years after operation. An autopsy showed no evidence Twenty patients are of any recurrence. living, one of whom has a metastasis in the supracIavicuIar area. This wou1d be 73 per cent who have gone five years or more without any evidence of recurrence.“O From these scanty and contradictory reports it seems that further series so treated wouId be of tremendous importance. ANDROGENS OF
AS
AN
CANCER
ADJUNCT OF
THE
TO TREATMENT BREAST
Androgens in the form of testosterone proprionate has been used (I ) therapeuticaIIy in advanced or recurrent cases and (2) prophyIacticaIIy beginning at the time of radica1 breast operation. The author has recentIy reviewed his experience with this agent on advanced breast cancer. 31 Further experience has served onIy to confirm the opinions previousIy expressed. In soft tissue involvement, such as chest waI1, opposite breast, liver, Iung, etc., the results in a smaI1 percentage of cases may be very gratifying for varying periods of time but probably several months at the most. In the greatest percentage of cases, however, no effect can be noted on the progression of the disease. With metastatic bone disease no effect may be noted or the patient might have striking pain reIief with recaMication of the Iesion or the anomalous circumstance of cIinica1 improvement but no roentgenographic change or even roentgenographic progression may take pIace. As with
Jones-Carcinoma
702
soft tissue involvement, any improvement either cIinica1 or actuaI is Iimited in time. The usua1 dosage is IOO mg. three times weekly although a satisfactory response may sometimes be obtained with Iess. It is our beIief that if one obtains a favorabIe response, the treatment should be continued indefiniteIy. The occasiona briIIiant response to testosterone has Ied to its rather widespread use as the primary agent in treating metastatic inoperabIe breast cancer. In view of the variability of response and the generaIIy satisfactory benefit from roentgen therapy it is we11 to emphasize that in we11 IocaIized Iesions, either soft tissue or bone, roentgen therapy is stiI1 the best therapeutic agent. On the other hand, in roentgen faiIure and in generaIized disease testosterone may produce an occasiona astounding result. The first and most ardent advocate of prophyIactic testosterone was Prudente.32 He treated his first patient in ApriI, 1939. His resu1t.s after three, four and five years indicate an increase of IOO per cent compared with end resuIts of previous years. A later communication33 substantiated his earIier impression. The dosage of testosterone varied in Prudente’s series from 23 to 173 mg. per week. PREGNANCY
FOLLOWING
RADICAL
BREAST
OPERATION
It is generaIIy agreed that pregnancy acceIerates the growth of carcinoma aIready present. Westberg, however, on the basis of experience in Sweden has presented a contrary point of view. Be this as it may, pregnancy subsequent to radica1 breast operation might Iight up otherwise Iatent metastases. The foIIowing three case reports wiI1 iIIustrate this possibiIity. CASE I. M. B., No. 72,736, aged forty, had had a Ieft radicaI breast operation in January, 1936. The patient was first seen in the OutPatient Department at Johns Hopkins HOSpita1 on November 4, 1936. FoIIowing the radicaI operation she did we11 until two months
of Breast prior to her admission to the hospita1 when she observed a considerabIe sweIIing of her arm and hand. An examination showed extensive local recurrence in the chest wall and the axiIIa. She was aIso thought to have pIura1 effusion from metastasis. The uterus was enIarged to the size of tweIve weeks’ pregnancy. In spite of a therapeutic abortion on November death was prompt. Recurrence 11, 1936, appearing at the onset of pregnancy and the viruIent and short clinica course are suggestive of a causa1 reIationship.
CASE II. M. G. No. 73,430, aged thirtynine, had a radica1 breast operation on September 22, 1936. PathoIoglc examination showed meduIIary carcinoma without metastasis to the axiIIa. About January IS, 1937, she had severe pain in the back and in the right Ieg. She Iost considerabIe weight and did not menstruate from the time of her discharge in 1936. She was readmitted to Johns Hopkins Hospital on February 2, 1937 foIlowing a spontaneous abortion at home. She died very soon thereafter with generaIized cancinomatoses. CASE II. H. G., No. 270,786, aged twentynine, had a right radica1 mastectomy performed by Dr. BIaIock on September I, 1942. PathoIogic examination reveaIed comedo carcinoma with regional metastases. The patient was seen on ApriI 4, 1944, for a routine check-up. There was no evidence of metastases or IocaI recurrence. However, she was found to be six months’ pregnant. The baby was deIivered uneventfuIIy. By August 1st there was a cough and chest pain. X-ray revealed many metastatic Iesions in the ribs. She died on October 18,
1944. Trout35 reported two cases of pregnancy occurring four and six years, respectivery, after radical mastectomy. In each instance, simuItaneousIy with the pregnancy, carcinoma occurred in the opposite ‘breast. Trout circuIarized severa of his surgica1 friends and coIIected seventeen cases of pregnancy subsequent to radical mastectomy. In thirteen of these carcinoma deveIoped in the opposite breast. Broemis36.37 reported substantiaIIy simiIar resuIts although Westberg reported severa instances of pregnancy subsequent to breast surgery without untoward effect. It is our belief, therefore, that pregnancy American
Journal
of Surgery
Jones-Carcinoma subsequent to radical breast operation exposes the patient to an unnecessary risk. It is indeed an additional argument for the routine use of castration at the time of radicaI operation in women in the childbearing age. At the very Ieast, the surgeon may be expected to assume the responsibility of advising his patients against pregnancy folIowing radicaI breast surgery. PRESENT
STATUS
OF
THERAPY
FOR
BREAST
CANCER
On the basis of the aforementioned review- it is suggested that the average individual with cancer of the breast shouId be subjected to immediate radica1 operation without preliminary irradiation. In inoperabIe cases or those of borderhne operability irradiation, sometimes alone or combined with surgery, has much to offer incIuding the possibiIity of a five-year cure. On the basis of experience it is not possible to demonstrate any improvement in five-year end resuIts from the routine use of postoperative prophylactic therapy. From theoretic considerations and from a review of the Iiterature, there is reason to believe that routine prophyIactic castrations, particuIarly in the chiId-bearing age, is to be seriously considered in the routine treatment of breast cancer. Furthermore, this procedure prevents pregnancv which, in some instances at least, is associated with widespread metastasis following radica1 breast surgery. Androgens play an important part in otherwise hopeless breast cancer but at the present time they are to be recommended only in those cases not suitable for high voltage, roentgen therapy or in cases of roentgen faiIure. KEFERENCES I. bIaryIand
State Department of Health. Bureau of Vita1 Statistics. Persona1 communication. 2. HARRINGTON, S. W. SurgicaI rates of radical mastectomy for uniIateraI and biIatera1 carcinoma of the breast. Surgery, 19: 154, 1946. 3. WEBSTER, H., PHII.LIPS, W. H., NODELIIO~FER,L., OLIVER, M. and PARSONS, E. Examination of the breasts and pelvic organs in apparentIy weI1 women. Illinois M. J., 89: 239, 1946.
of Breast
703
4. HAAGENSEN,C. D. and STOUT, A. P. C;Ircinom:r of the breast. Ann. Surg., I 10: 801, 1942. 5. BRAUSFIELD, J. W. and CASTIGLIANO, S. G. The inadequacy of simple mastectomy for inoperable cancer of the breast. Am. J. Roentpenol., 47: 748, 1942. 6. ADAIR, FRAF;K E. The effect of preoperative irradiation in primary operable cancer of the breast. Am. J. Roentgenol., 35: 359, ,936. 7. COHN, L. C. Carcinoma of the female breast. Arch. SW+,
44: 715,
194.2.
8. I~ALBERSTAEDTER,L. and HocH~~A~, II. The artificial menopause and cancer of the breast. J. A.M. A., 131: 810, 1946. g. BEATSON, G. T. On the treatment of inoperable cases of the mammaI: suggestions for a new method of treatment, with iIIustrative cases. Lancet, 2: ro4, 1896. to. THOMPSON, A. Analysis of cases in which oophorectomy was performed for inoperative carcinoma of the breast. &it. A4. J., 2: 1538, 1902. LI. LETT, H. AnaIysis of gg cases of inoperable carcinoma of breast treated by oophorectomy. Lancet, I: 227, 1905. 12. BEATSON, G. T. Treatment of inopcrablc carcinoma of female mammaI. Glasgotu M. J., 76: 8r, 1911. 13. DRESSER, RICHARD. Effect of ovarian irradiation as bone metastases of cancer of breast. Am. J. Roentgenok 35: 384, 1926. 14. HOFFMAK, W. J. Spontaneous Disappearance of metastatic nodules from carcinoma of breast foIIowing irradiation of ovaries. S. Clin. North America, 13: 494-498, 1933. 15. SMITH, E. G. SteriIization in carcinoma of breast. Am. J. Roentgenol., 36: 65, 1936. 16. \VITHERSPOON, J. T. Roentgen irradiation of ovaries as suppIement to surgical and radium therapy for mammary cancer. Arch. Sure., 33: 554. 1936. 17. RITVO, M. and PETERSON, 0. S., JR. Regression of bone metastases after ovarian steriIization. Am. J. Roentgenol., 5 I : 220, 1944. 18. TREVES, N., ABELS, J. C., WOO~ARD, H. Q. and FARROW, J. H. Effects of orchiectomy on primary and metastatic carcinoma. Surg., 6)nec. (*+ Obst., 79: 589, 1944. 19. ADAIR, F. E., TREVES, NORMAN, FARROU., .I. tI. and SCHARNAGEL, I. M. CIinicaI eIfccts of surgica1 and x-ray castration in mammary cancer. J. A. M. A., 128: 161, 1945. 20. AHLBO~~, H. Castration by rorntgen rays as auxilliary treatment in radiotherapy of cancer mammae at radium Iemmet. Acts Radical I I: 614-633, 1930. 21. ZONDEK, B. and VON E\:IxR, N. Follikuiinausscheidung im Harn des Kindes, der Frau und des Mannes. Skand. Arch. F. Plysiol. 67: 259, ‘934. 22. ROBSON, J. M., MACGRCGOR, T. N., ILLIUCIWOHTH, R. E. and STEERE, N. Urinary excretion of estrogen administered under experimentat conditions and after the menopause. Brit. hl. J., 1: 888, 1934. 23. FRAIUK, R. T. TOLDRER~ER, M. A. and SPIBL~IA~;.
704
Jones-Carcinoma F.
Present
endocrine
diagnosis
J. A. M. A., 103: 393, 1934.
and
therapy.
24. LAKOCHE, G., SIMMONNET, H. and HVLT, J. A. Contribution a L’etude des Variations du Taut de la Folliculine Chrr la Femme. Compt. rend. Sot. de biol., I 13: 286, 1933. 25. HERRELL, W. E. ReIative incidence of oophorectomy in women with and without carcinoma of breast. Am. J. Cancer, 29: 65, 1937. 26. OLCH, I. V. Menopausal age in women with cancer of the breast. Am. J. Cancer, 30: 563-566, 1937. 27. TAYLOR, G. W. Evaluation of ovarian sterilization for breast cancer. .%rg., @net. @YObst., 68: 452, ‘939. 28. TAYLOR, G. W. Persona1 communication, 1948. 29. HORSELY, Gtiu W. Treatment of cancer of the breast in pre-menopausal patients with radical amduthtion and bilateral oophorectomy. Am. J.
Surg., 125: 203, 1947. 30. HORSLEY, GUY W. Personal communication,
1948.
of Breast 31. JONES, I&WARD
W., JR. Testosterone in the treatment of advanced breast cancer. South M. J.,
4,: 4 1948.
12. PRUDENTE. A. Post-ooerative ProuhvIaxis of Rccurrent Mammary Cancer with Testosterone Propionate. Surg., Gynec. 0 Obst., 80: 575, 1945. 33. PRUDENTE, A. Personal communication, 1947. 34. WESTBERG, S. V. Prognosis of Breast Cancer for Pregnant and Nursing Women. Stockholm, 1946. Hakan, Ohlssons, Boktryckeri. 35. TROUT, H. H. The remaining breast after radical removal of the opposite side for carcinoma. Surg., Gynec. to Obst., 34: 630, 1922. 36. BROMEIS, H. Der Einffuss Schwangerschaft und der StiIIperiode auf den Brustkrebs und die Richlelinien des ArzIichen HandeIns. Deutscbe Ztscbr. f. Cbir., 252: 294, 1939. 37. BROMEIS, H. Zur Frage einer neuen Schwangerschaft nach RadikaI operation eines Brustkrebs. 1
&
”
Cbirurg., I I : 662, 1939.
SOLITARY, uniIatera1 cysts in women undergoing menopause that show recent increase in size are often malignant. PavIovsky et al. recently studied I I I cases of cancer of the breast and found that in I I per cent of them there was an associated condition of chronic cystic mastitis. (Richard
A. Leonardo,
M.D.)
American
Journal
of
Surgery