Carcinoma of the breast. Recurrence and survival in 203 patients

CARCINOMA OF THE BREAST Recurrence and Suruiual in 203 Patients

A. H. ROBNET, M.D., THOMAS E. JONES, M.D., and JOHN B. HAZARD, M.D.

T HROUGH the past fifty years, an enor- mous volume of fact and theory concerning the treatment of carcinoma of the breast has accumulated in the medical literature. Unfortunately, reported series have contained widely varied results and diverse conclusions regarding specific forms of therapy, so that unanimity of opinion between accepted authorities is lacking. The confusion and conflict of belief is wholly due to the lack of a universally accepted, reliable classification of the different types and stages of carcinoma of the breast. It is almost impossible, at the present time, to find two large series of cases from different sources that use an identical system of classification. Until this goal can be reached, the confusion of fact and belief will persist.

This report is a statistical study of the five-, seven-, and ten-year-survival rates of 203 consecutive cases of carcinoma of the breast in women who were treated surgically, some with and some without sup- plementary postoperative roentgen therapy. Each case has been carefully evaluated and classified, and the specification of each classification clearly outlined. So-called “Paget’s cancer” of the breast has not been included. Secondary facts gleaned from the case his- tories have been compiled to aid in evaluating factors influencing the prognosis. Recurrence rates are presented.

AGE INCIDENCE

Of the patients, 10.3 per cent were between the ages of 20 and 40 years; 58.1 per cent were between 40 and 60, and 31.6 per cent were more than 60 years of age.

On the basis of population figures pub-

From the Cleveland Clinic and the Frank E.

Received for publication, February 21, 1950. Bunts Educational Institute, Cleveland, Ohio.

lished by the Department of Commerce12 for 1940, it is estimated that, of the female population older than 20 years, 49 per cent were between the ages of 20 and 40, roughly 41.0 per cent were between 40 and 64, and 10 per cent were more than 60 years.

When the figures of Table 1 and Table 2 are presented graphically, the relation of the two curves, in agreement with the belief of Nathanson and Welch, suggests a gradu- ally increasing incidence of carcinoma of the breast with increase of age (Fig. 1).

FAMILIAL HISTORY

Unfortunately, the familial history of cancer did not specify the location of the neoplasm in all cases. Only 24.6 per cent of the patients were aware of malignant tumor in blood relatives.

TABLE 1

AGE INCIDENCE OF CARCINOMA OF THE BREAST

Per cent of total Age group Number (203)

20-29 1 30-39 20 40-49 58 50-59 60 60-69 45 70-80 19

TOTAL 203 -

0.5 9.8

28.5 29.6 22.2

9.4

100.0 -

TABLE 2

FEMALE POPULATION U.S.A. 1940‘2

Approximate Age group flumber Percentage

20-29 11,541,419 27.0

40-44 4.368.708 10.0 30-39 9,971,794 22.0

45-54 7:550:052 18.0 55-64 5,163,025 13.0 65-74 3,209,134 8.0 75- 1,404,606 2.0

7581 CANCER September 1950

I I I I I I I 1 1 I I

10 20 30 40 50 60 70 80 90 I( AGE

FIG. 1. Age distribution.

FERTILITY

Of the patients, 51.1 per cent had had one or more pregnancies.

SYMPTOMS

The presenting symptom in the majority of cases (67.0 per cent) was the single com- plaint of a painless mass in the breast. As- sociated with the mass in 27.9 per cent was pain, usually mild and intermittent. Discharge from the nipple was infrequent, occurring in only 4.6 per cent, and usually noted as a few drops of pinkish-yellow fluid. Pain as a single presenting symptom was rare (0.5 per cent). Six of the 203 cases were discovered at the time of examination for unrelated complaints.

LOCATION OF THE MASS

The location of the mass was roughly the same in the two breasts, with the incidence as given in Table 3. Simultaneously noted bilateral carcinoma occurred in five cases (2.4 per cent). The relation between survival and location will be discussed sub- sequen tly.

CLASSIFICATION

T o evaluate the success of different forms of therapy in carcinoma of the breast, both a relative and an absolute standard must

be used. The relative standard is used when the results of different forms of therapy are compared.

Unfortunately, comparison of different forms of therapy has resulted in conflicting claims and beliefs. This is due in large measure to the failure to designate clearly the extent of the disease in the cases treated and to segregate cases according to the extent of the disease when the therapy was applied. T h e results of a series composed of cases treated early in the disease cannot be used to evaluate a mode of therapy used in a series composed of moderately or far- advanced disease. T o overcome this prob- lem, a satisfactory classification with a con- sistent degree of prognostic accuracy must be used.

I t is generally conceded that the most important prognostic determinant, omit- ting remote metastases, is the extent of lymph-node involvement. Second to this are: (1) cutaneous involvement; ( 2 ) the degree of local fixation of tumor to the chest wall; (3) the type of carcinoma present as determined by the pathologist.

The various classifications to further prognostic accuracy and to provide a satisfactory basis for study of results of therapy are founded upon these factors. None of the classifications currently in use is com- pletely satisfactory.

Steinthal Classification. The Steinthal classification depends principally upon a clinical estimate of the degree of axillary lymph-node involvement. Taylor and Bruce, in a careful study, have found a dis- crepancy of 28 per cent between clinical

TABLE 3

LOCATION OF MASS

%, Right breast %, Left breast (47.5%) (52.5%)

Lateral quadrants 28.4 31.4 Upper 25.4 27.4 Lower 3.0 4.0

Medial quadrants 11.7 14.2

Lower 1.9 4.9 Central 7.4 6.9

Upper 9.8 9.3

CARCINOMA OF THE BREAST - Robnet t , Jones, dr Hazard [759

estimate and pathological finding of axillary metastases. Others have stated that the presence of axillary metastases can be detected clinically in only 50 per cent of the cases,g hence, variation in reported results that utilized this classification is readily probability. understood.

postoperative roentgen-ray therapy. Some of the divisions are too few in numerical content to be statistically conclusive; how- ever, the results obtained permit analysis and conclusions within the limits of factual

Columns of figures often fail to create a

Portrnann Classification. In an effort to exclude this inaccuracy, Portmann pro- posed a combined clinical-pathological classification utilizing, as one of the major criteria, the degree of axillary lymph-node involvement determined by microscopic examination of all lymph nodes obtained. Nevertheless, prognostic inaccuracies and conflicting results occur with this improved classification.

In explanation of these inaccuracies, the work of Saphir is of importance. In serial- section restudy of thirty cases in which axillary lymph nodes had been reported as uninvolved on routine microscopic examination, he found that 33.3 per cent contained carcinoma cells. Furthermore, and most often overlooked, has been the factor of involvement of the internal mammary lymph nodes. In a study of five cases, Handley and Thackray found that in two cases with involvement of the axillary nodes, there was also involvement of the internal mammary nodes; in two cases the axillary nodes were uninvolved but internal mammary nodes contained metastatic carcinoma; and, in one case, there was no lymph-node involvement.

The use of a classification based solely upon the pathological character of the neoplasm suffers from the lack of general agreement among pathologists as to definition of the different types2 and grades, the tendency of several types to coexist, and the factors noted in the preceding paragraphs.

Classification by Mode of Treatment. In addition to showing survival figures as a whole for each group (Portmann classification) and type (pathological classification), there has been further subdivision to show survival €or those treated by surgery alone and those treated by surgery and immediate

- definite, lasting impression; therefore, graphic representations have been pre- pared. In these representations, survival is graphed as a band created by a line of maximum survival and a line of minimum survival.

The figure of minimum survival is the per cent of the total treated known to be alive. Since some of the patients are known to have died of unrelated causes, have been lost, or have been operative deaths, a figure of maximum survival has been reached by deducting these cases from the total treated, obtaining the "net treated' and calculating the per cent of the net treated known to be alive.

NATURAL COURSE OF THE DISEASE

The most absolute criterion of the success of treatment of any disease depends upon the mathematical relation between the survival of treated patients and the survival of untreated patients. A table of the natural course of the disease adapted from the work of Daland has been used, forming a basis of comparison on each survival graph. Of a total of 100 cases, Daland found the average duration of life from time of the initial symptom to be forty and a half months and the mean duration of

TABLE 4

NATURAL COURSE OF THE DISEASE' 100 Cases

Year fromfirst sVmptom % Suruiual

1 79 2 60 3 40 4 30

13 0


TABLE 5

OVER-ALL SURVEY

% % No. Total Net

Cases Folloiued M i n . of 5 Yrs. Total cases treated Operative deaths Lost Dead. unrelated causes Net cases followed 5 yrs.

Dead of disease Alive

Cases Follwwed Min. of 7 Yrs. Total cases treated Operative deaths Lost Dead, unrelated causes Net cases followed 7 yrs.


Cases Follmoed Min. of 10 Yrs. Total cases treated Operative deaths Lost Dead, unrelated causes Net cases followed 10 yrs.

Dead of cancer Alive

203 100.0 4 2.0

22 10.8 15 7.4

162 79.8 100.0 75 32.1 46.3 87 47.7 53.7

149 100.0 23 2.0 21 14.1 11 7.4

114 76.5 100.0 65 43.6 57.0 49 32.9 43.0

the disease (50 per cent alive and 50 per cent dead), thirty months. This is con- firmed by the work of Wade, whose figure for the mean duration OE life from the time of first symptom is thirty-two and six-tenths moil ths.

SURVIVAL RATES

The 203 cases, analyzed as a whole, yield Table 5 and Fig. 2.

The five-year-survival rate as demonstrated in the over-all survey is between

I I I I I I I I I

I 2 3 4 5 6 7 % 9 I0 YEARS SURVIVAL

FIG. 2. “Over-all” suwey (203 cases).

47.7 and 53.7 per cent, the seven-year-, between 32.9 and 43.0 per cent; and the ten- year-, between 26.7 and 34.8 per cent. Between the fifth and tenth year, the mortality rate in this series has been demonstrated to increase by approximately 20 per cent. The fallacy of the “cures” reported on the basis of a five-year study is clearly indicated.

Szmiivnl by Groups (Portmann Clnssifica- lion). The 203 cases have been subdivided into groups I, 11, 111, and IV, utilizing the Portmann classification, and these groups have been subdivided into those that were treated surgically and those that were treated by surgery supplemented with postoperative roentgen-ray therapy.

The method of grouping according to the Portmann classification is:

Group I Skin: ‘Tumor:

Metastases:

Group I1 Skin: Tumor:

Metastases:

Group 111 Skin:

Tumor:

Metastases:

Not involved. Localized in breast and movable. None in axillary nodes or elsewhere.

Not involved. Localized in breast and movable. Few axillary nodes involved (less than five in this series), no other metastases.

Edematous, brawny, red, with induration not obviously due to infection; extensive ulceration; multiple secondary nodules. Diffusely infiltrating breast; fixation of tumor or breast to chest wall; edema of breast; secondary tumor. Many axillary lymph nodes involved or fixed; no clinical or roentgenological evi- dences of distant metastases.

I i

a 40

20

'"1 , , , I ,

1 2 3 4 5 ; ; i l 9 ; 0 YEARS SURVIVAL

FIG. 3. Group I , all cases (fifty-nine).

j , , , , , , , , I 1 2 5 4 5 6 7 8 9 1 0

YEARS SURVIVAL

FIG. 5. t h rrnpy (se7ien cases).

Ch-oup I , surgery and roentgen-ray

90

80

70

z m W 8 so 0

40

30

20

IOi I

, , I l l I

I 2 3 4 5 6 7 8 9 10 YEARS SURVIVAL

FIG. 7. cases).

Group ZI, surgery only (f ifty-six

100

90

80

70

I- 60 2

# 50

24i 3

I0

I 1 1 1 1 1 1 1 1 1 1

1 2 3 4 5 6 7 8 9 1 0 YEARS SURVIVAL

FIG. 4. Group I , surgery only (fifty-two cases).

I 'O1

YEARS SURVIVAL

FIG. 6. G ~ o u p ZZ, all cases (seventy-one).

I

I- E

t Y

20 301

I I I I , , , , , ,

I 2 3 4 5 6 7 8 9 10 YEARS SURVIVAL

FIG. 8. ray therapy (fifteen cases).

Group I I , surgery and roentgen-


Group IV Skin: As in any other

group. Tumor: As in any other

group. Metastases: Axillary and supra-

clavicular 1 y m p h nodes extensively involved and clinical or roentgenological evi- dences of more distant metastases.

Under this classification, the 203 cases are distributed as in Table 6.

TABLE 6

CLASSIFICATION OF CASES Portmann Criteria

Group Number Per cent

I I1 111 IV

59 29.1 71 34.9 70

3 34.5

1.5 - - TOTAL 203 100.0

Group I . (See Table 7, Group I.) Of the four group-I cases dead of the disease in five years, medullary carcinoma was found in three and carcinoma simplex in one. Five of the cases followed for seven years died, two of scirrhous, two of medul-

lary, and one of carcinoma simplex: and of the four dead in the group followed for ten years, two died of scirrhous, and two of medullary carcinoma. The distribution of the pathological type among the group-I cases dead of the disease does not clarify the influence of type of carcinoma upon survival.

It is in the group-I cases that 100.0 per cent survival or cure should be realized. By definition, the disease is localized to the breast without axillary-node involvement, yet the mortality over a five-year period is 6.8 to 8.3 per cent. Several explanations must be considered.

1. Undetected axillary-node involvement might have existed. This error could be corrected through the use of serial sections of the axillary nodes as indicated by Saphir's work, with conversion of some of group I to group I1 or group 111.

2. Metastases might have involved the internal mammary or supraclavicular nodes without concomitant or prior involvement of axillary nodes as noted by Handley et al.4~ 5

3. Remote metastases via vascular emboli might have been undetected.

4. Radical mastectomy might have been inadequate.

TABLE 7

FIVE-, SEVEN-, AND TEN-YEAR RESULTS IN PORTMANN-GROUPS I, 11, AND I11 ~ _ _ _ _ _ ~~

All cases Operation only Operation B pastop. x-rays

Total % Of % Of Total % Of % Of Total % Of % Of Group and Number no. total net no. total net no. total net

Group Z (59) 5-Year results

Total number treated Operative deaths Lost Dead, unrelated causes Net followed 5 yrs.


7-Year results Total number treated Ouerative deaths List Dead, unrelated causes Net followed 7 yrs.


59 2 5 4

48 4

44

46 2 8 3

33 5

28

100.0 3.4 8.5 6.8

81.3 6.8

74.5

100.0 4.3 8.6 6.5

80.6 10.8 69.8

52 2 4 3

100.0 43 8.3 3

91.7 40

43 2 3 8

100.0 29 15.2 4 84.8 26

100.0 7 3.8 0 7.8 1 5.8 1

82.6 100.0 5 5.8 6.9 1

76.8 93.1 4

100.0 3 4.7 0 6.9 0

18.7 0 69.7 100.0 3

9.4 13.7 1 60.3 86.3 2

100.0 0.0

14.3 14.3 71.4 100.0 14.3 20.0 57.1 80.0

100.0 0.0 0.0 0.0

100.0 100.0 33.3 33.3 66.7 66.7

CARCINOMA OF THE BREAST - Robnett , Jones, 6. Hazard [763

TABLE 7-Continued

FIVE-, SEVEN-, AND TEN-YEAR RESULTS IN PORTMANN-GROUPS I, 11, AND I11

Group and Number

10-Year results Total number treated Operative deaths Lost Dead, unrelated causes Net followed 10 yrs. Dead of disease

Alive

Group ZZ (77) 5-Year results



7-Year results Total number treated Operative deaths Lost Dead, unrelated causes Net followed 7 yrs.




Group IZZ (70) 5- Year re.rults







All cases Operation o n b Operation @ postop. x-rays

Total % Of % Of Total % Of % Of Total % Of % Of no. total net no. total net no. total net

25 1 4 1

19 4

15

71 1 9 5

56 22 34

54 1

10 5

38 22 16

32 1 6 3

22 13 9

70 1 7 6

56 47 9

48 0 3 3

42 37

5

32 0 2 3

27 27 0

100.0 4.0

16.0 4.0

76.0 16.0 60.0

100.0 1.4

12.7 7.0

78.9 30.9 48.0

100.0 1.8

18.5 9.3

70.4 40.7 29.7

100.0 3.1

18.8 9.3

68.8 43.7 25.1

100.0 1.5

10.0 8.5

80.0 67.1 12.9

100.0 0.0 6.2 6.2

87.6 77.1 10.5

100.0 0.0 6.2 9.5

84.3 84.3 0.0

100.0 21.1 78.9

100.0 39.3 60.7

100.0 57.8 42.2

100.0 59.0 41 .O

100.0 83.9 16.1

100.0 88.1 11.9

100.0 100.0

0.0

22 1 4 1

16 3

13

56 1 7 5

43 20 23

43 1 7 5

30 18 12

25 1 3 3

18 12 6

41 1 5 4

31 25 6

30 0 3 2

25 23 2

20 0 2 2

16 16 0

100.0 4.5

18.0 4.5

73.0 13.6 59.4

100.0 1.8

12.5 8.9

76.8 35.7 41.1

100.0 2.3

16.3 11.6 69.8 41.8 28.0

100.0 4.0

12.0 12.0 72.0 48.0 24.0

100.0 2.4

12.2 9.8

75.6 60.9 14.7

100.0 0.0

10.0 6.7

83.3 76.6 6.7

100.0 0.0

10.0 10.0 80.0 80.0 0.0

100.0 18.7 81.3

100.0 46.5 53.5

100.0 60.0 40.0

100.0 66.7 33.3

100.0 80.6 19.4

100.0 92.0 8.0

100.0 100.0

0.0

3 0 0 0 3 1 2

15 0 2 0

13 2

11

11 0 3 0 8 4 4

7 0 3 0 4 1 3

29 0 2 2

25 22 3

18 0 0 1

17 14 3

12 0 0 0

11 11 0

100.0 0.0 0.0 0.0

100.0 33.3 66.7

100.0 0.0

13.3 0.0

86.7 13.3 73.4

100.0 0.0

27.2 0.0

72.8 36.3 36.5

100.0 0.0

42.9 0.0

57.1 14.3 42.8

100.0 0.0 6.9 6.9

86.2 75.9 10.3

100.0 0.0 0.0 5.6

94.4 77.8 16.6

100.0 0.0 0.0 8.3

91.7 91.7

100.0 33.3 66.7

100.0 15.4 84.6

100.0 50.0 50.0

100.0 25.0 75.0

100.0 88.0 12.0

100.0 82.4 17.6

100.0 100.0

0.0 0.0


Since only seven of this group were re- cipients of postoperative roentgen-ray therapy, no conclusion can be drawn as to its value.

Group ZI. (See Table 7, Group 11.) With the primary tumor localized in the breast and movable, with secondary neoplasm detected in less than five axillary nodes by microscopic study, and with tech- nically sound surgical treatment, it is aston- ishing to note a decline in the five-, seven-, and ten-year survivals of the magnitude perceived when group-I and group-I1 graphs are compared. The explanation of this survival decline clearly indicates that in the group-I1 cases, the extent of the disease as regards spread to lymphatics other than the axillary, dissemination to remote parts, or microscopically undetected axillary-node involvement is greater than sug- gested by the clinical and pathological studies. Certainly, one must again question the adequacy of the accepted radical mastectomy as it is conventionally performed.

With only fifteen of the seventy-one cases treated by postoperative roentgen-ray therapy and with two of these lost for five-year, three for seven-year, and three for ten-year evaluation, the results are not statistically significant, although the trend of the curve of survival suggests that postoperative treatment is of value in those cases of group 11. The five-year-minimum survival of those treated surgically with supplemental postoperative roentgen-ray therapy is 32.3 per cent greater than those treated with surgical therapy only, the seven-year-minimum survival 8.5 per cent greater, and the ten- year-minimum survival, 18.8 per cent greater.

Group ZZZ. (See Table 7, Group 111.j Postoperative roentgen-ray therapy admin- istered to twenty-nine of the seventy cases in this group failed to improve the ten-year survival but suggestively improved the maximum seven-year survival by 9.6 per cent. Balancing this apparent benefit of roentgen-ray therapy in the patients traced seven years is a 7.4 per cent greater maximum survival of patients treated with oper-

TABLE 8

YEARLY SURVIVAL OF GROUP-111 CASES FOLLOWED FIVE YEARS

Operotwn OPeralion

No . % No. % No. % x-rays ___-- (111 cases only

Total 56 100.0 31 100.0 25 100.0 Survived

1 yr. 44 78.5 25 80.6 19 76.0 2 yr. 33 58.9 20 64.5 13 52.0 3 yr. 20 35.7 1 1 35.4 9 36.0 4 yr. 14 25.0 6 19.6 8 32.0 5 yr. 10 17.8 6 19.6 4 16.0

....................................................... Cases not incl.

Operative deaths 1 1 0

Lost 7 5 2 Dead, other

cause 6 4 2

ation alone in the group followed five years. Hence, it is difficult to accept as conclusive the benefit of postoperative roentgen-ray therapy in this group. (Table 7, Group 111.)

The results obtained with the group-I11 cases merited further, more detailed, comparison with the natural course of the disease. A year-by-year study (Table 8) for the cases followed for five years is graphically presented and demonstrates with clarity the futility of the surgical and the surgical-plus- roentgen-ray therapy that was used.

Group ZV. Group IV included only three cases, of which one could not be traced. All were treated by operation and postoperative roentgen-ray therapy. None survived a five-year period.

This group includes those cases with known remote metastases present at the time of treatment. Unquestionably, it should be much larger, for in it should fall many of the group11 and group-111 cases in which remote metastatic disease must have been present at the time of surgery. These unsuspected remote metastases might have been detected through the use of screening roentgenograms of bone and chest, but such a procedure is still not eco- nomically feasible and would certainly fail to demonstrate an ultimately lethal but still microscopic nidus of neoplasm.

CLASSIFICATION BY PATHOLOGICAL TYPE

Study of cancer of the breast on the basis of the pathological type present, whether

CARCINOMA OF THE BREAST - Robnett, Jones, 6. Hazard [765

The results portrayed in Table 9 reveal the study is based on summation of the characteristics of the individual cells, upon the architectural arrangement of the cells, upon the degree of fibrosis and tissue reac- tion to the neoplasm, or upon a combination of these factors, results in variations in reported results. This is due to the individual differences in interpretation and evaluation of the specimens examined.

TABLE 9

DISTRIBUTION AND FIVE-YEAR EVALUATION BY PATHOLOGICAL

TYPE

Net no. followed

Type No. % 5 yrs. % Dead % Alive

Scirrhous 63 31.0 48 51.7 48.3 Sim lex 67 33.0 54 50.0 50.0 Mezullary 39 19.2 39 51.3 48.7 Adeno- 32 15.8 32 44.0 56.0 Coil-gland 1 0.5 Unclassified* 1 0.5

TOTAL 203 100.0 - -

* Primary removed elsewhere but axillary nodes contained secondary neoplasm.

In this series, different architectural groupings of neoplastic cells could be re- peatedly demonstrated in the same or different sections from a single lesion. Though the method may be subject to just criticism, the individual lesions have been classified here according to the most dedifferentiated architectural type discovered in the study of each lesion. The order of malignancy has been assumed to be: scirrhous, simplex, medullary, adeno-, mucinous, intraduct, and coil-gland. Intraduct and mucinous carcinomas were not encountered in this series, the absence of the former perhaps being due to the omission of all cases of Paget’s disease.

SURVIVAL BY PATHOLOGICAL TYPE

Over a five-year-postoperative period, the cases have been grouped by pathological type. The cases lost because of operative death, those that could not be traced, and those known to have died of unrelated causes have been eliminated. The survival percentages then have been calculated upon the net followed five years, and represent the maximum-survival rates.

no significant difference in maximum five- year survival of the commonest pathological types with the method of classification used. Mucinous, intraduct, and coil-gland types could not be evaluated because of their small number or absence from the series.

A further subdivision of the pathological types has been made upon the basis of the Portmann classification (Table lo).

In the scirrhous type, the five-year group-I minimum survival is 73.4 per cent, the group-I11 is 14.3 per cent. This is roughly paralleled in the other groups for the five-, seven-, and ten-year studies. From this must be concluded that survival is pri- marily dependent upon the extent of the lesion and may be modified only to a lesser degree by the pathological type of lesion present, as determined by methods used in this series and in so far as scirrhous, simplex, medullary, and adenocarcinoma are concerned.

Duration and Surzkal . . Duration of the disease (Table 11) prior to treatment is based upon the patient’s estimate of the time of appearance of the first symptom.

The method of determining duration is grossly inaccurate for each individual case, but, in comparing these two groups, a crude index is available.

Over-a11 survival in those cases treated within six months of the appearance of the initial symptom bettered by almost 13.0 per cent the survival of the cases treated more than a year after the noted onset of the disease. It is surprising that the difference is not greater, and this suggests a slow distal spread of the disease.

The relation of duration to extent of the disease is manifest by the ratio of groups I and 11 to groups 111 and IV in the two time units. In the time unit “under six months,” groups I and I1 include a total of 73.8 per cent of the cases, whereas, in the time unit “over twelve months,” groups I and I1 account for only 49.0 per cent of the total cases. The equivalence of the survival rates in similar groups in each of the time


TABLE 10

FIVE-, SEVEN-, AND TEN-YEAR RESULTS IN SCIRRHOUS, SIMPLEX, MEDULLARY, AND ADENOCARCINOMA

Group Z Group I1 Group Irr

Total % Of Type of Carcinoma no. total

% Of Total % Of % Of Total net no. total net no.

Scirrhous Carcinoma * (61) 5-Tear results

Total treated Operative deaths Lost Dead, unrelated causes Net followed 5 yrs.


7-%ar results Total treated Operative deaths Lost Dead, unrelated causes Net followed 7 yrs.


10- Year results Total treated Operative deaths Lost Dead, unrelated causes Net followed 10 yrs.


Carcinoma Simp1e.u t ( 6 7 ) 5-Year results

Total treated Operative deaths Lost Dead, unrelated causes Net followed 5 yrs. Dead of disease

Alive

7-Year results Total treated Operative deaths Lost Dead, unrelated causes Net followed 7 yrs.




15 0 2 2

11 0

11

13 0 2 2 9 2 7

6 0 1 0 5 2 3

18 0 1 0

17 1

16

11 0 2 0 9 1 8

6 0 1 0 5 0 5

100.0 0.0

13.3 13.3 73.4 0.0

13.4

100.0 0.0

15.4 15.4 69.2 15.4 53.8

100.0 0.0

16.6 0.0

84.4 33.3 51.1

100.0 0.0 5.5 0.0

94.5 5.5

89.0

100.0 0.0

18.9 0.0

81.1 9.5

71.6

100.0 0.0

16.6 0.0

83.4 0.0

83.4

100.0 0.0

100.0

100.0 22.2 77.8

100.0 40.0 60.0

100.0 5.8

94.2

100.0 11.1 88.9

100.0 0.0 .

100.0 5

18 0 3 3

12 4 8

12 0 3 3 6 2 4

6 ‘0 2 0 4 3 1

24 1 3 2

18 9 9

17 1 4 2

10 5 5

12 1 3 2 6 1

100.0 0.0

16.7 16.7 66.6 22.2 44.4

100.0 0.0

25.0 25.0 50.0 16.7 33.3

100.0 0.0

33.3 0.0

66.7 50.0 16.6

100.0 4.1

12.5 8.4

75.0 37.5 37.5

100.0 5.9

23.6 11.8 58.7 29.35 29.35

100.0 8.3

25.0 16.7 50.0 8.3

41.7

100.0 33.3 66.7

100.0 33.3 66.7

100.0 75.0 55.0

100.0 50.0 50.0

100.0 50.0 50.0

100.0 16.6 83.4

28 0 2 3

23 19 4

15 0 1 1

13 11 2

12 0 1 1

10 10 0

24 1 3 1

19 17 2

16 0 0 1

15 13 2

11 0 0 1

10 10 0

%Of %Of total net

100.0 0.0 7.1

10.8 82.1 100.0 67.8 82.6 14.3 17.4

100.0 0.0 6.6 6.6

86.8 100.0 73.6 84.6 13.2 15.4

100.0 0.0 8.3 . .-

8.3 83.4 100.0 83.4 100.0

0.0 0.0

100.0 4.1

12.5 4.1

79.3 100.0 70.9 89.5 8.4 10.5

100.0 0.0 0.0 6.3

93.7 100.0 81.1 86.7 12.6 13.3

100.0 0.0 0.0 9.1

90.9 100.0 90.9 100.0 0.0 0.0

* Group IV included two cases; dead within three years. t Group IV included 1 case, lost a t the end of two years.

CARCINOMA OF THE BREAST . Robnett, Jones, Q Hazard [767 TABLE 10-Continued

FIVE-, SEVEN-, AND TEN-YEAR RESULTS IN SCIRRHOUS, SIMPLEX, MEDULLARY, AND ADENOCARCINOMA

~- ________ Group I Group II Group III

Total % Of % Of Total % Of % Of Total % Of ’% Of T y p e of Carcinoma no. total net no. total net no. total net

Mtzdullary Carcinoma (39) 5-Tear results

Total treated Operative deaths Lost Dead, unrelated causes Net followed 5 yrs.


7- Year results Total treated Operative deaths Lost Dead, unrelated causes Net followed 7 yrs.


10-liar results Total treated Operative deaths Lost Dead, unrelated causes Net followed 10 yrs.


Adenocarcinoma (32) &Tear results

Total treated Operative deaths Lost Dead, unrelated causes Net followed 5 vrs.


7-Tear results Total treated Operative deaths Lost Dead, unrelated causes Net followed 7 yrs.




19 2 0 1

16 3

13

14 2 2 0

10 1 9

8 1 1 0 6 1 5

7 0 1 1 5 1 4

5 0 1 1 3 0 3

3 0 1 1 1 0 1

100.0 10.5 0.0 5.3

84.2 15.9 68.3

100.0 14.2 14.2

0.0 71.6 7.1

64.5

100.0 12.5 12.5 0.0

75.0 12.5 62.5

100.0 0.0

14.2 14.2 77.6 14.2 63.4

100.0 0.0

20.0 20.0 60.0 0.0

60.0

100.0 0.0

33.3 33.3 33.4 0.0

33.4

100.0 18.7 81.3

100.0 10.0 90.0

100.0 16.6 83.4

100.0 20.0 80.0

100.0 0.0

100.0

100.0 0.0

100.0

13 100.0 7 100.0 0 0.0 0 0.0 2 15.3 1 14.2 0 0.0 0 0.0

11.0 84.7 100.0 6 85.8 100.0 5 30.7 45.4 6 85.8 100.0 6 54.0 54.6 0 0.0 0.0

8 100.0 3 100.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 8 100.0 100.0 3 100.0 100.0 5 62.5 62.5 3 100.0 100.0 3 37.5 37.5 0 0.0 0.0

1 100.0 0 0.0 0 0.0 0 0.0 1 100.0 100.0 1 100.0 100.0 0 0.0 0.0

15 100.0 10 100.0 0 0.0 0 0.0 1 6.7 1 10.0 0 0.0 2 20.0

14 93.3 100.0 7 70.0 100.0 3 20.1 21.4 4 40.0 57.1

11 73.2 78.6 3 30.0 42.9

12 100.0 7 100.0 0 0.0 0 0.0 2 16.7 1 14.3 0 0.0 1 14.3

10 83.3 100.0 5 71.4 100.0 6 50.0 60.0 4 57.1 80.0 4 33.3 40.0 1 14.3 20.0

7 100.0 3 100.0 0 0.0 0 0.0 1 14.3 0 0.0 0 0.0 1 33.4 6 85.7 100.0 2 66.6 100.0 4 57.1 66.6 2 66.6 100.0 2 20.6 33.4 0 0.0 0.0

I I

YEARS SURVIVAL

FIG. 9. Group 111, all cases (seventy). YEARS SURVIVAL

FIG. 10. cases).

Group IIZ, surgery only (forty-one

1 2 3 4 5 6 7 8 9 10 YEARS SURVIVAL

FIG. 11. ray therapy (twenty-nine cases).

Group IZZ, surgery and roentgen-

30-

M-

'O1 I

I I I I

I 2 3 4 5 YEARS SURVIVAL

FIG. 13. Group I I I , yearly survival of cases with surgery only (thirty-one) followed five years.

30-

20-

10

I I I I I I 2 3 4 5

YEARS SURVWAL

FIG. 12. cases (fifty-six) followed five years.

Group IIZ, yearly survival of all

40-

30-

20-

I ' O i 1 I

I I I I I

I 2 3 4 5 YEARS SURVIVAL

FIG. 14. Group 111, yearly suruiwal of cases with szugery and roentgen-my therapy (twenty-fiite) followed fiwe years.

CARCINOMA OF THE BREAST - Robnett , Jones, dr Hazard [769

TABLE l l cludes size as an important prognostic de-

Location and Suriiival. Those cases in

DURATION AND SURVIVAL terminant in groups I1 and 111. Portmann Classification

Less llian 6 mos. More fhan 12 mas. 92 cases 51 cases

% 5-Yr. % Of % 5,Yr. Groufi 2 2 survrval total xuivrwal

I 36.9 88.2 13.7 100.0 11 36.9 61.7 35.3 72.2 111 26.2 16.6 47.1 16.6 1 v 0.0 0.0 3.9 0.0

TOTAL 100.0 59.8 100.0 47.1

units is evident; therefore, the prognostic value of the duration factor is automati- cally included in the Portmann classification.

T h e maximum diameter of the lesion (Table 12) as recorded in the pathologist’s description of the gross specimen is used as an index of the macro- scopic size of the tumor.

The over-all-survival rates of those lesions 4.0 cm. in maximum diameter is 46.3 per cent less than the survival rate of lesions with a maximum diameter of no more than 2.0 cm. Although the group-I-survival rate i n each size category is relatively con- stant, the group-11- and group-111- survival rates in the two size categories vary mark- edly, with a survival decrease of the magnitude of 37.2 per cent to 21.0 per cent respectively in the groups with the larger lesion. The decline in survival rate is equalIy marked when the larger lesions are compared with the smaller lesions of the same pathological type.

T o the Portmann classification must he added a factor that more specifically in-

Size and Survival.

TABLE 12

SIZE AND SURVIVAL Portmann Classification

0 to 2.0 cm. Over 4.0 cm. 46 cases 60 cases

% Of % 5-Yr. % Of % 5-Yr. Grouj total survival total survival

I 45.7 05.2 16.7 on0 ~

I1 39.1 8313 21.7 46.1 111 15.2 42.8 58.3 21.8 IV 0.0 0.0 3.3 0.0

TOTAL 100.0 82.6 100.0 38.3

which the neoplasm was present in the medial hemisphere of the breast compose 26.1 per cent of the series. (Table 13.)

In the over-all analysis of the 203 cases, the comparable five-year-survival figures are: group I, 74.5 per cent; group 11, 48.0 per cent; group 111, 12.9 per cent, and group IV, 0.0 per cent (Table 7). The most appreciable difference occurs in group 11, where there is a 20.2 per cent lower survival rate in the medial-hemisphere group. Since the over-all figure represents a mean of survival rates of medial and lateral hemi- spheres, the survival rate from lateral-hemisphere carcinoma is proportionately higher than the rate obtained for the medial location.

TABLE 13

CARCINOMA OF MEDIAL HEMISPHERE Five-Year Evaluation

G o u p 6’ number

I ( l 8 ) I I (18) I I I (16) I V (1) _________ % % % %

Total 100.0 100.0 10D.O 100.0 Lost 5.6 11.1 12.5 0.0 Dead, unrelated cause 11.1 0.0 6.3 0.0 Followed 5 yrs. 83.3 88.9 81.2 100.0 Dead of disease 5.6 61.1 68.7 100.0 Alive 77.7 27.8 12.5 0.0

Since the operative treatment for either location includes axillary dissection, but also, in each incidence, neglects the internal mammary nodes, it is probable on the basis of proximity that involvement of internal mammary nodes occurs earlier and more frequently with carcinoma that involves the medial hemisphere. This accounts for the lower survival rate here demonstrated.

LOCAL RECURRENCE

Local recurrence is defined as the reap- pearance within the scope of the operative field of the same type of neoplasm as that removed at the initial surgical treatment. The operative field includes the chest wall and axilla of the side treated, exclusive of


TABLE 14

LOCAL RECURRENCE

% % No. Total Net

Total cases treated 203 100.0 Operative deaths 4 2.0 1.mt 22 in.8 ~. ~~. Dead, unrelated causes 1s 7.4 Net cases followed 5 yrs. 162 79.8 100.0 Cases with local recurrence 30 14.2 18.5

bony structure. The opposite breast, supraclavicular nodes, and adjacent tissues be- yond the field of dissection are considered as “remote” and are not included in this study of local recurrence.

Local recurrence (Table 14) in the 203 patients equals 14.2 per cent, and this, corrected by eliminating cases not followed five years, rises to an incidence of 18.5 per cent, indicating that roughly one of every five cases exhibited local recurrence.

Time of Recurrence. T h e time of appearance of the local recurrence has been obtained, and, calculating from the time of initial surgery, is, by postoperative year, as shown in Table 15.

It is to be noted that the figures for each year include the recurrences of previous years. The fact that 7.7 per cent of the local recurrences occurred after five years is somewhat misleading, since it represents but two cases of the total of 203. Since 93.3 per cent of the recurrences were detected within five years, the prognosis as regards appearance of local recurrence after five years is very good.

Some of the patients with local recurrence were treated only five years ago, so that

TABLE 15

TIME OF RECURRENCE

Cases

NO. % Total 30 100.0 Recurrence in less than:

1 Yr. 9 30.0 2 Yrs. 16 53.3 3 Yrs. 20 66.6 4 Yrs. 27 90.0 5 Yrs. 28 93.3

10 Yrs. 29 96.7 14 Yrs. 30 100.0

Table 16 is complete for all cases for the first five years only.

Twelve of the thirty patients with local recurrence had received postoperative roentgen-ray therapy instituted immedi- ately after initial surgery. All recurrences in this group appeared in a maximum of three years, with average time of recurrence one and one-third years. Nine of the twelve were in group 111.

Of the eighteen patients with recurrences who did not receive immediate postoperative roentgen-ray therapy, eight were of group 111, and (eliminating the recurrence thirteen years after operation) the average time of recurrence was one and forty-eight huzdreths years.

TABLE 16

SURVIVAL OF CASES WITH LOCAL RECURRENCE

From Date of Operation ___

Cases

N d

min. followed Survived

Total Lost 5 yrs. Yrs. No . %

30 3 27 1 24 2 20 3 15 5 11 7 5 9 4

10 2 14 1

88.8 74.0 55.5 40.6 18.5 14.7

7.4 3.7 __

Comparing the group-I11 cases that did receive immediate postoperative roentgen- ray therapy with those that did not, no significant difference is found in the time of recurrence or in the survival time.

T h e recurrences were treated by excision, radon seeds, radiation, and a combination of the three, and no conclusion can be drawn as to respective worth of the forms of treatment.

T h e recurrence rate (Table 17) is in direct relation to the extent of the disease, that is, the degree of local involvement by the tumor and the extent of lymphatic involvement. This is quite in accord with results of Hoopes and McGraw who, in a study of 246 cases of carcinoma of the breast, found 6.1 Der cent recurrence in the ab-

CARCINOMA OF THE BREAST

TABLE 17

LOCAL RECURRENCE BY GROUP Portmann Classification*

-- Local % % Total

Croup Net no. recuw. Net no. no. recurr.

I 48 3 6.2 10.0 I1 56 11 19.6 36.7 I l l 56 15 26.7 50.0 IV 2 1 50.0 3.3

TOTAL 162 30 18.5 100.0

* Based on net number followed minimum of 5 years.

sence of axillary metastases and 20.8 per cent in the presence of axillary involvement.

Modified Radical Mastectomy and Re - currence. In some of the patients where advanced age, severe cardiovascular disease, or other illnesses have indicated the least t i aumatic and briefest possible operative procedure, the pectoral muscles were not removed, but axillary dissection was done. The incidence of local recurrence in this group is contrasted with the incidence of local recurrence in the larger group treated by classical radical mastectomy with removal of the pectoral muscles and axillary dissection. (Table 18.)

Although the group in which the muscles were not removed is too small to permit complete statistical acceptance, the incidence of recurrence is similar to that found in the group in which the muscles were removed.

One of the interesting revelations from the records studied is that of a patient afflicted with a group-I carcinoma of the breast who was treated surgically. At initial operation, the breast was removed, the in- sertion of the pectoralis muscle divided, the axillary dissection completed, and then the continuity of the pectoralis muscle re-es- I ablished. Thirteen years later, a recurrence was found and removed from the line of previous section of the pectoralis muscle and the muscles removed. The patient has been followed one year since the last operation and shows no evidence of other recurrence.

Despite the equivalent rate of local recurrence in the two groups, the survival rates reveal that, with the exception of the

Robnett, Jones, &i Hazard 1771

group-I cases, there is a slightly higher percentage survival over five, seven, and ten years in those cases treated by classical radical mastectomy. Had all of the cases treated without removal of pectoral muscles been subjected to classical radical mastectomy, the over-all survival rate might have been improved, although the operative mortality might have increased.

Fundamentally, every recurrence is due to failure to extirpate surgically or to de- stroy by roentgen-ray therapy all neoplastic cells. Implantation of malignant cells into innocent zones at the time of surgery occurs, and probably is the mechanism by which very early recurrences are produced.

The direct, marked relation of the degree of lymphatic involvement to the incidencc of local recurrence (Table 18) strongly suggests that, for the most part, the retained tumor cells must exist in lymphatics of tissue unremoved at time of radical mastectomy. These lymphatics may be of the un- excised skin, of the chest wall, of the internal mammary or supraclavicular nodes, or of an inadequately dissected axilla, or of more remote zones.

The normal route of lymphatic flow is from the capillary lymphatics of the skin to the subareolar plexus, into the circum- areolar plexus, through the superficial fascia1 plexus overlying the pectoral muscles, and thence via lymphatic vessels to the ipsilateral nodes, or secondarily to the supraclavicular nodes, internal mammary nodes, and to the contralateral axillary nodes. Obstruction to this normal route of flow does occur with blockage of cortical sinuses of lymph nodes, and may result in retrograde lymphatic drainage with per- meation of lymphatics by neoplasm or lym-

TABLE 18

LOCAL RECURRENCE BY TYPE OPERATION*

Local ieciirrence

Operation Net no. No. yo Net ~- ~-

Muscles removed 136 25 18.3 Muscles not removed 26 5 19.3

* Based on net number followed minimum of 5 years.

TOTAL 162 30 -


phatic emboli.* This phenomenon was noted by Gilchrist and David in their study of carcinoma of the rectum.

The relation of lymphatic involvement to local recurrence is most adequately ex- plained by the mechanism of retrograde lymphatic flow with extension of neoplastic cells, or seeding of malignant emboli from an obstructed lymph node to a more distal structure.

CONCLUSION

Some mode of evaluating the degree of involvement of the internal mammary nodes is urgently needed, and a safe method of extirpating the internal mammary nodes should be developed and made a part of radical mastectomy.

SUMMARY

1 . In the series of 203 cases presented, the over-all five-year-minimum survival equals 47.7 per cent; the minimum seven-year survival equals 32.9 per cent; the minimum

An adequate basis €or the comparison of ten-year survival equals 26.7 per cent. the results of different forms of therapy,

2. The extent of the disease is a more im- and therapy by different groups, is urgently portant prognostic factor than the patho- needed and should be universally adopted. logical type present. Among the variables used in classifying the

disease should be included an adeauate 3. recurrence to be Princi- sampling of all lymph nodes, as weil as pally related to the degree Of lYmPh-node factors from the physical examination as to location, measured size of the lesion, cuta- 4. Individual group survivals may be neous involvement, fixation, type of neo- satisfactorily determined under the Port- plasm present, and the age of the patient. mann classification.

REFERENCES

1. DALAND, E. M.: Untreated cancer of breast. Surg., Gynec. b Obst. 44: 264-268, 1927.

2. GESCHICKTER, C. F.: Diseases of the Breast; Diagnosis, Pathology, Treatment, 2d ed. Philadel- phia. J. B. Lippincott Company, 1945; p. 410.

3. GILCHRIST, R. K., and DAVID, V. C.: Lymphatic spread of carcinoma of rectum. Ann. Surg. 108:

4. HANDLEY, R. S., and THACKRAY, A. C.: Invasion of the internal mammary lymph glands in carcinoma of the breast. Brit. J. Cancer 1: 15-20, 1947.

5. HANDLEY, R. S., and THACKRAY, A. C.: The internal mammary lymph chain in carcinoma of the breast; study of 50 cases. Lancet 2: 276-278, 1949.

6. HOOPES, B. F., and MCGRAW, A. B.: Halsted radical mastectomy; 5-year results in 246 consecutive operations a t the same clinic. Surgeiy 12: 892- 905, 1942.

7. NATHANSON, I. T., and WELCH, C. E.: Life ex- pectancy and iucidence of malignant disease; carcinoma of the breast. Am. J. Cancer 28: 40-53, 1936.

621-642, 1938.

8. OLIVER, D. R., and SUGARBAKER, E. D.: Signifi- cance of skin recurrences following radical mastectomy. Surg., Gynec. Q Obst . 85: 360-367, 1947.

9. PORTMANN, U. V.: Clinical and pathologic criteria as basis for classifying cases of primary cancer of breast. Cleueland C h . Quart . 10: 41-47, 1943.

10. SAPHIR, O., and AMROMIN, G. D.: Obscure axillary lymph node metastasis in carcinoma of breast. A m . J. Path. 24: 726-727, 1948.

11. TAYLOR, G. W., and BRUCE, N. H.: Prognostic factors in carcinoma of breast. New England J. A4ed. 222: 790-792, 1940.

12. UNITED STATES BUREAU OF THE CENSUS: Cur- rent Population Reports. Series P-20. No. 30. Wash- ington. Government Printing Office. 1940; p. 11.

13. WADE, P.: Untreated carcinoma of breast; comparison with results of treatment of advanced breast carcinoma. Brit . J. Radiol. 19: 272-280, 1946.

Documents

Carcinoma of the breast. Recurrence and survival in 203 patients