prognosis of mammary carcinoma in young women

PROGNOSIS OF MAMMARY CARCINOMA I N YOUNG WOMEN

IAN MACDONALD, RI.D., A N D N. ELANE \VILCOX, M.S .

VER the years a succession of authors have 0 perpetuated the belief that mammary carcinoma occurring before 30 years of age is attended by a more ominous prognosis than in older age groups. Ewing stated that “before S O years of age mammary cancer is extremely fatal, so that some surgeons prefer not to oper- ate during this period.” Lewison, Trimble, and Griffith endorsed this position with their opinion that women less than 40 years of age with cancer of the breast have a comparatively poorer prognosis than those more than 40. Geschickter cites several studies, including those of Nathanson a n d Welch and Lee and Kraine, as well as his own, that indicate that age is a significant factor in determining prognosis of patients with breast cancer. All of the latter authors have concluded that life expec- tancy is less in women developing mammary carcinoma before agc 40 than in those women who have breast cancer at a later age. This position has been challenged” or opposed2, 3,

9, 13 by others after more or less critical analysis of the several intrinsic factors encountered in the management of breast cancer.

In their follow-up of 708 cases of mammary carcinonia Cliffton and Young noted five patients under 30 years of age, all of whom died less than onc ycar after mastectomy. Four oE these five were operated upon shortly post- Ixirtum and one in the third month of pregnancy. These investigators suggest that hor- monal changes accompanying pregnancy and lactation, conditions compatible with youth, iire to be considered in determining the prognosis of breast cancer. h significant study was reported by de

(;holnoky, who collected seventy-three cases

From the Department of Surgery, School of Medicine, [Jniversity of Southern California, Los Angeles, Cali- fornia.

The authors are indebted to the following hospitals and to individual members of their attending staffs for assistance in obtaining follow-up data: California Hos- pital, Hollywood-Presbyterian Hospital, Hospital of the Good Samaritan, 1.0s Angeles General Hospital, Metho- dist Hospital, Queen of Angels Hospital, and S t . Vin- cent’s Hospital. We acknowledge particularly the help of the medical record librarians in each of the fore- going institutions.

Received for publication, August 1, 1955.

in women less than age 30 from hospitals in New York and Massachusetts who had a five- year survival of 40 per cent, and a ten-year survival of 37 per cent. de Cholnoky suggests that, since carcinoma is not commonly found in the breasts of young women, it is often overlooked as a possible diagnosis of solid tumors 01 mammary origin a t a stage most amenable to definitive treatment. Data com- piled by Shimkin et al. is entirely contrary to the hypothesis of a low survival rate for young women with breast cancer. These investigators concluded that there are no consistent trends or differences in survival among successive age groups.

One of us9 concluded, from a study o l the records of more than twenty-six hundred patients in the archives of the American College of Surgeons, that prognosis was poorest in mammary carcinoma when the disease developed during or just after menopause. This study also indicated that, excluding those lesions developing during pregnancy or lactation, carcinoma of the breast diagnosed prior to age 30 was actually associated with a more favorable natural history than at other ages, except in very elderly women. These conclu- sions were termed invalid by Geschickter, based as they were on a sample of case records in the archives submitted by a large number of contributing hospitals and individuals.

The present study was undertaken to obtain further evidence on this subject, by obtaining as large a sample as possible of mammary carcinoma developing at 30 years of age or younger, from a single community (Los An- geles) .

~ ~ F X H O I ) S

Table 1 indicates the incidence of breast cancer as i t exists in various age groups of the total populatiori. Women younger than 35 years contribute less than twenty-six cases per 100,000 population in any of four metropoli- tan areas. Wotnen 65 years or older yield from 260 exes of mammary ciircinoina per 100,000 in Pitts1)iirgIi to 404 per 100,000 persons i n the San Francisco-Alameda area.

282 CANCER March-April 1956 VOl. 9

TABLE 1

PER 100,000 POPULATION* FEMALE BREAST-CANCER INCIDENCE RATES, BY AGE AND BY CITY,

All Less than 15-24 25-34 35-44 45-64 65 or Ages 15 yr. Yr. Yr. Yr. Yr. more yr.

Chicago, 1947 77 6 0 1 7 18.7 84.0 168.8 269.6 Philadelphia, 1948 78.0 0 3 3 19.8 71.9 162.5 301.3 San Francisco & Alameda

counties, 1947 97 7 0 0 .0 16 9 82.2 208 5 404.3 Pittsburgh 60 7 0 1.6 24.9 52.6 144.9 260.1

Publ. No. 65, 126, 152, 244). Washington, D. C. Government Printing Office. p. 32; 152, p. 36; 244, p. 34.

* PUBLIC HEALTH SERVICE. FEDERAL SECURITY AGFNCY: Cancer Mortality Series (Public Health Service 1951-1952; No. 65, p. 42; 126,

Because of the rarity of carcinoma of the breast in women younger than age 30, the review of a significant series of patients was achieved by collecting data from seven major hospitals in Los Angeles.

A census of cases of breast cancer in women 30 years of age or younger was thus obtained from diagnostic indexes and records of hospitals maintaining 35 per cent of the total beds in licensed general hospitals in the County of Los Angeles. Histological diagnosis was estab- lished in each patient; fifty-five were found to have mammary carcinoma, thus providing the basis for this study. (Sarcomas and several epithelial lesions interpreted as ductal or lobu- lar preinvasive carcinoma were excluded.) Of these fifty-five patients, two have been lost to all follow-up efforts since the time of their original treatment. They have been included as failures in the “total experience” represented in Table 2 and excluded in other tabulations of determinate order. The data on these patients were first collected from 1948 to early in 1950, and thus the most recent follow-up enables us to present results in terms of survival without recurrence at a minimum of five years for some, at ten years for others, and at more than ten years for still another fraction.

The method employed for determining extent of disease is the basic expression of its natural history represented by the following classification, according to pathological find- i ngs :

Stage IP: disease limited to the breast, with skin involvement zero or minimal.

Stage IIP: histological evidence of axillary node or nodes involved by metastasis, or more than minimal cutaneous spread, including ulceration.

Stage 111: metastasis beyond axillary nodes, including supraclavicular nodes, or fixation of the primary lesion to the pectoral fascia.

End results are presented in terms of: CLIN- ICAL CONTROL: (1) determinate, by medical examination; ( 2 ) determinate, without medical examination; (3) indeterminate; SURVIVAL: indeterminate.

The term “clinical control” is employed rather than the designation “cured,” because of the notorious frequency of deaths from disease in mammary carcinoma after the arbitrary five-year period. Determinate (absolute) results count untraced patients as failures, while indeterminate (relative) figures exclude those untraced. In this group, the determinate results are valid, as only two of fifty-five patients (3.6 per cent) are untraced.

FINDINGS

The total experience is shown in Table 2, in the form recommended by the Joint Com- mittee on Reporting of End Results in Cancer. Counting the two untraced patients as “failures,’’ sixteen of these women lived for five or more years without recurrence at any time, as verified by medical examination. Three other patients were “apparently free of cancer” for five or more years, but without verification by examination. The determinate (absolute) degree of clinical control for five or more years was 35 per cent, although it was only 30 per cent by medical verification.

T h e indeterminate result (excluding two untraced patients) for apparent clinical control at five years was 36 per cent. The survival rate at five years, which includes two patients alive with disease, was 39.6 per cent.

Other results presented hereafter are based on survival rates only, with exclusion of the two untraced patients as indeterminate.

Stage of Disease. Of the fifty-three traced patients, forty-six had been subjected to radical mastectomy, and reports of gross and microscopic study of axillary nodes were avail-

No. 2

GENERAL SUMMARY __-_______ _________________ TOTAL EXPERIENCE-All patients applying

BREAST-CANCER PROGNOSIS IN YOUNG WOMEN Macdonald 6. Wilcox 283

Number of Cases

55 __--__--

Cases previously treated

a. Applied after treatment elsewhere, no evidence of cancer on admission or thereafter

SECTION A I Cases not previously treated

0

0

55

Without Microscopic

Proof -

~

SECTION B

Total __--

OTHER

e. Dead within five years of other causes without recurrence of cancer

-____ _______- ~ _ _ f. Dead, cancer present or died of complications of

treatment

0

32

~ ~~

b. Consultation only, no treatment requested 0 I SECTION A. Cases not previously treated

9. Dead-presence of cancer unknown

h. Living with cancer present at 5 years ________________-___---

Number of Cases

0

2

RESULTS AT E N D OF FIVE YEARS

k.

I. Living, continuously free of cancer, verified by

Untraced full five years, not classifiable in “d” or “j” -~ ____ __________

medical examination at 5 years

With Microscopic

Proof

0 _--

16

GROUP I

m. Living, apparently free of cancer, not verified by medical examination at 5 years

n. Living, successfully treated for recurrence, free of cancer at 5 years

GROUP I I

3

0

GROUP I l l

0 I 55 I

GROUP I V

TOTAL

c. Refused proffered treatment l o d. Untraced for full five years without recurrence at

last examination l 2

i. Living with condition unknown at 5 years l o j. Untraced full five years with cancer at last examin-

ation

I 55

I---

_____

284 CANCER March-dfwil 1956 Vol. 9

TABLE 3 STAGE OF DISEASE REL.4TED TO SURVIVAL

Survival, yr.

Total 5 or more Staae no. %, 1 5 5-9 10ormore KO. '7,

I P 20 37 .7 5 9 6 15 75 I IP 29 54.7 24 3 2 5 1 7

111 1 1 s 1 0 0 0 0 Not det 'd 3 5 8 0 1 2 3 too _- __ - - __ - TOTAL 53 100.0 30 13 10 73 43 .4

able. In three additional patients, microscopic proof of axillary nodal involvement was obtained, and in a fourth patient the recording of hard, fixed axillary nodes in a woman dying of disease less than one year after admission made her an obvious stage-I1 case at the time of operation. In three patients, the stage of disease was not determined; in one of these, axillary nodes were removed for biopsy and metastasis was not demonstrated, but this falls short of the evidence nececsary for accurate staging.

Shown in Table 3 i s the distribution of patients, as well as their survival, by stage of disease on admission. In almost four out ot ten of these young women, the neoplasm was still limited to the breast by histological evidence (stage IP); in 56.5 per cent there was demonstrable extension beyond the heact, either regional (stage IIP) or distant (stage IJI). Of the three patients in whom adequate histological study of axillary nodes was not available, one has survived for nine years and two for more than ten years. All three are thus probably stage-IP cases, making the true incidence of stage-IP cases well over 40 per cent.

As in all studies of end results in breast cancer, the stage of disease was the most im- portant single factor in determining prognosis. Exactly 75 per cent of stage-IP cases and only 21 per cent of stage-IIP cases survived for five or more years. Assuming that the thrce un- staged cases surviving nine or more years were stage IP, the five-year survival becomes 80 per cent. For the entire group of fifty-three traced patients, the five-year-survival rate was 43.4 per cent.

T h e subsequent course of several oE the stage-I1 cases indicates that a more thorough preoperative survey would have indicated the presence of metastasis in various remote areas (supraclavicular, intrathoracic, or skeletal). One patient died forty-eight hours after radical mastectomy and autopsy revealed bulky hepatic metastasis; this patient is indicated as a stage-I11 case. In other instances, the cvi-

dence for remote metastasis on admission is less exact, and these are included as stage-11 cases.

Duration of Symptoms. T h e elapsed time from recognition of the first symptom, most often the presence of a lump in the hreast, to the time of admission is shown in arbitrary intervals in Table 4. T h e relationship ot duration of first symptom to survival for five or more years is presented in Table 5. T h e saiii- pies for duration of less than one month and more than twelve months are numerically inadequate, but the total sample divides almost equally by duration ot less than, or more than, six months. Ey this criterion oE delay, patients with earlier diagnosis had a five-year survival of 34 per cent, while those with reported duration of more than six months to as long as eighteen months had a survival rate of 54 per cent (Table 5).

Size of Primary Lesion. A more objective criterion of the earliness ot the local lesion is its spatial extent. In forty-eight of the traced patients, the size of the primary lesion had been recorded by the pathologist after gross examination of a surgical specimen. As indicated in Tables 6 and 7, there was no statisti- cal difference in survival [or five to nine years, or for ten or more ycars, whether the primary neoplasm was 2 cm. or less in average diameter or in the range from more than 2 cm. to 5 cm. IE the lesion in the breast was more than 5 cm. in diameter, the survival rate fell sharply.

T h e three samples are statistically comparable, and the survival rate for five or more years with increasing extent of mammary involvement was 53 per cent, 55 per cent, and 15 per cent.

P~egnancy and Lactation. I n eight patients, the disease developed during pregnancy or lactation: in five, survival was less than five years; thrce have survived without evident recurrence for periods of six to twelve years.

TABLE 4 DURATION OF SYMPTOMS

Survival, yr.

Duration, Less than 10 or mo. 5 5-9 more Tota 1

(1 1 1 1 3 1 - 2 6 6-12

3 4 23 7 5 4 16

1;

> 12 4 3 1 8 3 Not recorded 2 1

TOTAL 30 13 10 53

- __ -- --- --

No. 2 BREAST-CANCER PROGNOSIS IN YOUNG WOMEN . Macdonald 6. Wilcox 285

TABLE 5 PERCENTAGE SURVIVAL FIVE OR MORE

YEARS, RELATED T O DURATION OF SYMPTOMS

Survival for 5 or more years __l__l_--l_- Duration,

<1 2 : 3 66’ mo. Ratio %

I34 > 1-<6 7 : 2 3 6-12

>12 4 : 8 50

The survival for five or more years in this small group was better than one in three. Two of these women became pregnant again after mastectomy; one developed fulminating recurrence and died before delivery, while the other survived for four years before dying with metastasis.

It the cases developing during pregnancy and lactation are excluded, the five-year survival is almost identical with that for the entire group, or 44.4 per cent compared to 43.4 per cent.

Ldocatiori of Primary Lesion. As reported in larger series of cases, the left breast is more commonly affected than the right; in this group, the ratio was 28 : 24. Unfortunately, the lesion was not accurately localized within the breast in seventeen cases; for the remain- der, origin in the lateral, medial, and subareolar aleas is indicated in Table 8, together with corresponding survival rates for five or more years. No bilateral involvement, nor any instance ok subsequent contralateral lesion, was found.

Treatment. Of the fifty-three traced patients, radical mastectomy was done in fortysix, simple mastectomy or some variation thereof (such as one modified radical) in four, while irradiation was the only or principal treatment in three patients.

Ot the patients treated by radical mastectomy, twenty were stage-IP cases, of whom fifteen survived for five or more years; twenty- two were stage-IIP, with only three surviving more than five years. Two ot the simple mas- tectomies were on patients who had axillary nodes with metastasis; both procedures were supplemented by irradiation and both patients died in less than five years. In the other two patients subjected to simple mastectomy, survival exceeded five years for one patient and ten years for the other; in neither was there clinical or histological evidence available con-

cerning axillary node involvement. Of the three patients treated by irradiation, there was biopsy evidence of axillary metastasis in two, and both were dead in less than two years. The third patient, treated by irradiation alone, survived for more than ten years.

DISCUSSION

The data presented herein again demon- strate that mammary carcinoma in young women is attended by a somewhat more favorable prognosis than the average for all ages combined. The incidence of axillary node involvement (stage IIP) was 54.7 per cent; comparable figures from large series of cases of all ages are 68 per cent (Shimkin et al.), 78 per cent (Adair), 61 per cent (Harrington) and 70 per cent (Haagensen).

Survival for five or more years in this group of women 30 years of age or less was 43.4 per cent. This compares favorably with five-year results of 40.4 per cent reported by Shimkin et al. and 39.6 per cent by Adair. The minimum period of follow-up for the group of young women reported here was five years, but a majority of the survivors are without recurrence well beyond the five-year mark, and ten have survived for more than ten years without recurrence or metastasis.

The one respect in which survival rates fall below those generally reported is for stage-IIP cases; for twenty-nine such patients, five-year survival was only 21 per cent. This compares with survival rates of 30 to 38 per cent reported by the authors listed. This may indicate that the disease is more ominous than average in young women when the axillary nodes are involved.

It should be noted that this report includes the total fourteen-year experience of seven major hospitals for cancer of the breast in women 30 years of age or younger. While

TABLE 6 SIZE OF PRIMARY LESION, RELATED

TO SURVIVAL Survival, yr.

Size of primary ----------- lesion, 10 or

cm. <5 5-9 more Total

2 or < 8 6 3 17 >2-5 8 5 5 18 > 5 11 1 1 13 Not recorded 3 1 1 5

TOTAL 30 13 10 53 -- -- -- -

286 CANCER March-April 1956 VOl. 9

some of the patients with so-called stage-I1 cases probably harbored distant foci of disease that would have been demonstrable by careful surveys, the fact remains that forty-four of these fif ty-three young women were primarily treated by radical mastectomy. Three other patients seem to have had less radical treatment for reasons not related to local and regional extent of disease. Hence, forty-seven of fifty-three neoplasms, or almost 90 per cent, were technically, if not biologically, operable, a far higher rate than for all carcinomas of the breast.

There is no significant relationship between duration of first symptom before treatment and survival in this group of young women. One of uslo has previously offered evidence of the minor importance of early diagnosis of breast cancer in general, stressing the pre- dominant factor of biological predeterminism. In younger women, the influence of growth pattern on the delay interval is obvious; those patients seeking treatment less than six months after recognized onset include the majority with rapidly growing neoplasms, with local or regional manifestations so florid as to arouse the patient’s concern in the first several months. In contrast, those patients coming to treatment after a delay of six months to one year or even longer are weighted by neoplasms of less ominous growth pattern, including some of the lesions that are dilatory in respect to metastatic spread. For these reasons, early treatment in this group, or with a delay interval of less than six months, produced a five-year-survival rate of 34 per cent, while with longer intervals of delay in secur- ing treatment the survival rate was 54 per cent.

A more objective measure of an early primary lesion is its size, and here again the biology ol the neoplastic process is consider- ably more significant than its degree of space occupation. T h e considerable range of size represented by primary tumors 2 cm. or less in average diameter, compared with those

TABLE 7 PERCENTAGE SURVIVAL, FIVE OR MORE

YEARS, RELATED TO SIZE OF PRIMARY LESION

Size of primary Total %survival, lesion, no. 5 or more

cm. patients Yr. 2 or < 2-5 5

1 7 18 13

53 55 15

TABLE 8 LOCATION,OF PRIMARY LESION, RELATED

TO SURVIVAL Survival for 5 or more yr.

No. ____-______ Location patients No. %

Outer quadrants 27 1 7 62.9 Subareolar 3 0 0 .oo Inner quadrants 6 3 50.00 Not recorded 17 3 17.6

TOTAL 53 23 43.4 -- ___

from more than 2 cm. to 5 cm., show no difference in survival rates, both groups ex- ceeding 50 per cent. When the primary neoplasm exceeds 5 cm. in diameter, there is a sharp decline in survival rate to 15 per cent.

The long-term survival of three of eight patients who developed their disease during pregnancy or lactation is further evidence that this fraction of women with mammary carcinoma should not be regarded as categorically inoperable.

T h e small number of patients reported here excludes any attempt at analysis of the thera- peutic methods employed. For stage-IP cases, however, radical mastectomy seems to be an effective method of treatment. Although this procedure produced only 21 per cent of five- year survivals in stage-IIP cases, it was never- theless a highly effective palliative procedure for the patients with uncontrolled disease, few of whom developed local or regional recur- rences. In view of the considerable tissue dos- age employed in the current vogue of simple mastectomy and local-regional irradiation and the greater hazard of late sequelae in these younger women, radical mastectomy should be the primary treatment of choice.

SUMMARY

The total experience of seven major hospitals in the City of Los Angeles with carcinoma of the breast in women 30 years of age or younger has been reviewed. From 1936 to 1950, fifty-five such patients were admitted, fifty-three of whom have been traced for five or more years.

By relative incidence of stage-IP and stage- I IP cases, and by over-all survival for five or more years, the prognosis is somewhat more favorable in women 20 to 30 years of age than that reported in large series of patients of all ages.

As in older women, biological predetermin-

No. 2

ism is the dominant prognostic factor, rather than the time of treatment or the size of the primary lesion.

Carcinoma of the breast developing during pregnancy or lactation is not a categorical in-

BREAST-CANCER PROGNOSIS IN YOUNG WOMEN . Macdonald plr Wilcox 287

tlication of inoperability. These ~ o n i e i i should be advised against subsequent pregnancy.

Primary radical mastectomy should be the preferred treatment for mammary carcinoma in younger women.

REFERENCES

1. ADAIR, F. E.: Surgical problems involved in breast cancer. [Moynihan Lecture.] Ann. Roy. Coll. Surgeons

2. CHOLNOKY, T. DE: Mammary cancer in youth. Surg., Gynec. d7 Obst. 77: 55-60, 1943.

3. CLIFFTON, E. E., and YOUNG, L. E.: Carcinoma of the breast; five- to twenty-year follow-up following radical mastectomy. Am. J . Surg. 82: 185-190, 1951.

4. EWING, J.: Neoplastic Diseases; a Treatise on T u - mors, 4th ed. Philadelphia. W. B. Saunders Co. 1940;

5. GESCHICKTER, C. F.: Diseases of the Breast; Diag- nosis, Pathology, Treatment. Philadelphia. J. B. Lip- pincott Co. 1943.

6. HAACENSEN, C. D.: Carcinoma of the Breast. American Cancer Society, Inc. New York. 1950.

7. HARRINGTON, S. W.: Surgical treatment of carcinoma of the breast. J. Michigan M. SOC. 47: 41-50, 1948.

8. LEWISON, E. F.; TRIMBLE, F. H., and GRIFFITH,

Ellgland 4: 360-380, 1949.

p. 594.

P. C.: Results of surgical treatment of breast cancer at Johns Hopkins Hospital, 1935-1940. J. A. M . A.

9. MACDONALD, I.: Mammary carcinoma; a review of 2,636 cases. Surg., Gynec. Q Obst. 74: 75-82, 1942.

10. MACDONALD, I.: Biological predeterminism in human cancer. Surg., Gynec. dr Obst. 92: 443-452, 1951.

11. SANDERS, R. L., and POOL, R. M.: Carcinoma of the breast; review of 206 cases. Am. , I . Surg. 81: 193- 197, 1951.

12. SCHINZ, H. R., and BOTSZTEJN, C.: Die Abhangig- keit der Prognose der Mamma-Carcinome vom Tumor- stadium und voni Lebensalter anhand von 702 Fallen. Arta radiol. 28: 611-622, 1947.

13. SHIMKIN, M. B.; LUCIA, E. L.; STONE, R. S . , and BELL, H. G.: Cancer of the breast; analysis of frequency, distribution, and mortality at the University of Cali- fornia Hospital, 1918 to 1947, inclusive. Szcrg., Gynec. Q Obst. 94: 645-661, 1952.

153: 905-909, 1953.

prognosis of mammary carcinoma in young women

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