T H E QUALITY OF SURVIVAL IN BREAST CANCER: A CASE-CONTROL COMPARISON

THOMAS J. CRAIG, MD,* GEORGE W. COMSTOCK, M D , ~

AND PATRICIA B. GEISER, RN, M S ~

Quality of survival as defined by physical and psychosocial criteria was found to be remarkably similar among I34 breast cancer patients and 260 controls. Most of the cases had been diagnosed 5 or more years prior to this study. Physical disability was reported by 19% of the cases and 16% of the controls. T h e slight excess of disability among the cases was related to surgical treatment. There was no evidence of increased psycho-social disability among the cases. T h e prin- cipal effect of breast cancer was t o triple mortality over a 28-month period. In both cases and controls, subsequent mortality was associated with reports of disability and ill health on the questionnaire but not with psycho-social varia- bles, with the possible exception of a pessimistic view of the future.

Cancer 33:1451-1457, 1974.

N ASSESSING THE SUCCESS OF THERAPY FOR I cancer and other chronic diseases, more and more attention is being given to the quality of survival as an addition to the traditional quantity of survival indices. Some physicians have even gone so far as to imply that quality of survival may, to a greater or lesser extent, determine quantity of sur- viva1.2~7~10

The current interest in quality of survival has manifested itself in a variety of ways, from surveys of cancer patients aimed at mea- surement of current quality of survival7 to attempts to integrate consideration of qualita- tive factors into the systematic clinical fol- lowup examinations of patients treated for carcinoma.10 A major hindrance to many of these efforts, however, has been the lack of clarity and uniformity both in delfining “quality of survival” and in assessing it. Some studies have focused on purely functional in- dices such as the ability to carry out “normal”

From the Department of Psychiatry and Be- havioral Sciences, School of Medicine, Johns Hopkins University, t Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University, and the t Special Cancer Studies Section, National Cancer Institute.

Supported in part by Research Grant HS 00014 from the National Center for Health Services Research and Development, Research Grant MH 19844 from the National Institute of Mental Health, and Career Re- search Award HL 21,670 from the National Heart and Lung Institute, U.S. Department of Health, Education and Welfare.

Ave.. Chevv Chase. MD 20015. Address for reprints: Dr. Thomas J. Craig, 4630 Hunt

Received‘for publication August 1 5 , 1973.

activities,16 while others have attempted to include global indices of “attitudes” and in- terpersonal relationships.7 Likewise, some studies have relied primarily on the patients’ reports of survival quality,l6 while others have used a clinical interview7 as the primary tool for judging this outcome, despite some evidence indicating that the empathic posi- tion of the interviewer may result in a tend- ency to over-estimate extent and severity of disability in the patient.11 Most importantly, all of these studies have been limited to in- vestigations of the quality of the patient’s existence without comparisons with control groups from the same general populations.

If quality of survival is accepted as a legiti- mate index of outcome, the relationship be- tween various therapeutic procedures and subsequent quality of survival must be syste- matically appraised so that truly effective plans of management for these disorders may be developed, as described by Feinstein.9 This is especially true if two or more treatment pro- grams with different outcomes in terms of quality of survival are available for a given disease.

There is considerable controversy about the optimal surgical procedure for most cases of breast cancer.“15 The most common operation is still the radical mastectomy described over 60 years ago by Halsted and Meyer. This has been generally accepted in this country as the procedure of choice chiefly because no other procedure has yet been shown to be more effective. However, less extensive opera-

1451

1452 CANCER May 1974 Vol. 33

tions have been increasingly advocated in re- cent years, either alone or in conjunction with radiation therapy. Long-term survival with the lesser operation is claimed to, be equiva- lent to that of the radical mastectomy in selected cases. Furthermore, the less extensive tissue losses from the lesser procedures should reduce functional disability and disfigure- ment, thereby improving the quality of sur- vival.7 Proponents of these lesser operations stress the qualitative deficit suffered by the patient who receives radical surgery, while advocates of radical mastectomy have tended to minimize this aspect, as exemplified by Moore’s statement that “in our opinion the emotional and cosmetic hazards of radical mastectomy have been overemphasized in the literature.”lO

As recent reviews have indicated,3,4,e,E,l3,141 17-19 quantitative 5-year survival rates quoted for these procedures have varied widely from study to study. Survival may well depend more on patient selection, clinical state at time of surgery, and socio-economic status than on the therapeutic efficacy of the surgery itself.12

In view of the controversy over survival rates and the well-being of the patients, i t seemed desirable to investigate the quality of survival of women with breast cancer. Ideally, such a study should compare patients who had undergone radical surgery with those who had had a lesser procedure. However, since radical mastectomy is now the generally accepted pro- cedure €or primary breast cancer, i t would be difficult to assemble enough patients having lesser surgery for an adequate comparison. Moreover, in the absence of a controlled trial, patient selection could vitiate such a com- parison since the lesser procedure is chosen more often for women with advanced age or extensive disease. The present study was de- signed to compare the quality of survival of a group of breast cancer patients, as measured by functional, symptomatic, and attitudinal indices, with that of controls selected from the same general population. The question to be answered was whether breast cancer patients gave evidence of significantly greater impair- ment than controls.

MATERIALS AND METHODS

Washington County, the site of this study, is located in western Maryland. A non-official census of the entire county in July, 1963 enumerated 91,909 residents.5 Medical services

to this population are provided almost exclu- sively by private physicians; nearly all illnesses requiring hospitalization are treated in the Washington County Hospital, the only gen- eral hospital in the area. Patients with medical conditions requiring specialized procedures are occasionally referred to Baltimore, or Washington, D.C., but generally return for followup care to their family physician.

Patients with breast cancer were identi- fied from a county cancer registry which was begun in 1949 by the National Cancer In- stitute. I t is believed that better than 95% of all serious malignancies such as breast cancer, which generally require hospitalization at so,me point, were identified. T h e registry files provided basic clinical information including age at diagnosis, method of diagnosis, date of first physician visit, date of diagnosis, stage of disease at diagnosis, type of treatment re- ceived, and interval from earliest symptom to diagnosis. Study cases were defined as Cau- casian women over 30 years of age with breast cancer diagnosed prior to July, 1967 who were living in Washington County at the time of the survey from April to June, 1968 and who were identified in the non-official census taken in July, 1963. Thus, for practical pur- poses, the cases had to have lived in Washing- ton County for at least 5 years prior to the survey.

Two sets of controls were selected. Popula- tion controls, matched by sex and age to the cases, were chosen from the 1963 census lists of the county. With a separate random start for each selection, the lists were searched for the next Caucasian female with the same birth year as the case. In addition, each case was matched to a neighborhood control. In this situation, the control was matched to the case on the basis of sex, birth year, and enumera- tion district with the Caucasian woman living closest to the case. Both sets of controls had to be currently living in Washington County at the time of the survey, Population controls who had died or could not be located were replaced by other randomly selected controls. For neighborhood controls who were no longer living in Washington County, no attempt was made to select a replacement.

The 1963 census provided extensive demo- graphic and socio-economic information on bath cases and controls, including date of birth, marital status, educational level, re- ligion and frequency of religious attendance, smoking history, and household information

No. 5 SURVIVAL QUALITY IN BREAST CANCER * Craig et al. 1453

such as the numbers of persons and rooms in the households. Additional information was obtained from a mailed questionnaire. This consisted of 28 items dealing with two major sets of variables, the first set designed to elicit information concerning biological factors sus- pected of being related to the etiology of breast cancer, and the second concerned with the quality of existence currently enjoyed by cases and controls. It was decided to repre- sent the questionnaire as a general health sur- vey rather than identifying it as a breast can- cer survey because it was felt that the latter identification might introduce bias in terms of differential response by case and controls.

A total of 156 cases was found to meet study criteria and received questionnaires. Of this group, 134 (85.97") responded. Of the 22 non- responders, 8 (5.17" of the total) were too ill or senile to complete the questionnaire, while 11 (7.0%) could not be located by repeated mailings and other attempts at contact, and 3 (2.00/,,) refused. Of the 134 cases respond- ing, 123 (91.7%) returned mailed question- naires. Ten were interviewed by telephone and 1 was interviewed in person.

Because additional population controls were selected to match cases where the initial control was unavailable, a total of 176 eligible population controls was mailed questionnaires of whom 139 (79.0%) responded. The non- respondents consisted of 19 (10.87") who could not be located, 12 (6.87,) who refused, and 6 (3.4%) who were senile. Among the respon- dent group, 10 interviews (7.1 %) were com- pleted by telephone and none by home inter- views.

Six of the 156 persons selected a9 neighbor- hood controls had died prior to the survey. Of the 150 not known to have died, 121 (80.6%) responded. The 29 nonrespondents were evenly divided among 10 (6.67") who were senile, 9 (6.0%) who refused, and 10 (6.67") who could not be located. Of the respondents, 108 (89.3%) mailed in their responses. Nine (7.4%) were completed by telephone and 4 (3.37") by home interviews.

T h e final study group consisted of 134 cases, 139 population controls, and 121 neighbor- hood controls. If the study had been limited to complete trios, each consisting of a case, matched population control, and matched neighborhood control, the number of subjects would have been drastically reduced. Because extensive analyses showed no significant dif- ferences either between complete and incom-

plete trios, or between population and neigh- borhood controls, all 134 cases were used for the case group and all 260 controls were com- bined to form the control group.

RESULTS

The general characteristics of cases and controls are listed in Table 1. The median birth year for cases was 1907; for controls it was 1908. The distribution of all three groups by education is similar, although slightly fewer cases than controls had not gone to high school. Cases and controls differed signifi- cantly with respect to marital status. This dif- ference resulted entirely from the unusually high proportion of widowed, divorced, and separated women among the population con- trols. Although it cannot be proved, it is be- lieved that this sfinding was most likely a chance occurrence.

Cases and controls were compared on several additional characteristics, including adequacy of housing as measured by toilet facilities (a rough index of socio-economic status), source of drinking water, religious at- tendance, and smoking history. They were virtually identical on all these factors, indi- cating that the two groups were similar socio- economically.

Table 2 shows the response rates for the two general aspects of quality of survival, namely physical functioning, as measured by extent of disability and assessment of current health status, and psycho-social functioning,

TABLE 1. Demographic Characteristics of Cases and Controls

Cases Controls No. % No. %

TOTAL Decade 1930-

of birth 1920- 1910- 1900- 1890- 1880- 1870-

Years of 0-8 school 9-12

13 or more Not stated

Marital Married status W-S-D*

Single

134 100.0 260 100.0 2 1 . 5 4 1.5 9 6 .7 21 8.1

46 34.3 89 34.2 38 28.4 76 29.2 24 17.9 42 16.2 13 9.7 25 9 . 6 2 1.5 3 1.2

50 37.3 111 42.7 64 47.8 110 42.3 16 11.9 34 13.1 4 3.0 5 1.9

87 64.9 146 56.2 35 26.lt 101 38.8t 12 9 . 0 13 5.0

* Widowed, separated, or divorced. t p < .05, when tested as an isolated finding.

1454 CANCER May 1974 VOl. 33

TABLE 2. Disability and Attitudes of Cases and Controls

Cases Controls

134 100.0 260 100.0 No. % No. %

TOTAL Disability and

limitation

Health status

Employment

Attitude

View of future

Symptoms

None-sligh t Moderate-total

Not related to surgery Related to surgery

Not stated Excellent-good Fair Poor-very poor Not stated Currently employed Housewife only Formerly employed

Wishes to work Does not wish to work

Other

Happy Moderately happy Unhappy Other, not stated Present oriented Future oriented Pessimistic Other, not stated None Depression Other Not stated

101

21 5 7

74 46 14

42 46

12 30 4

113 7 8 6

45 76 5 8

19 28 84

2

-

75.4

15.7 3 . 7 5.2

55.2 34.3 10.4*

31.3 34.3

9 . 0 22.4 3 . 0

84.3 5 .2 6 . 0 4 . 5

33.6 56.7 3 .7 6 .0

14.2 20.9 62.7

1 . 5

-

207

42

79.6

16.2

11 152 89 10 9

65 82

14 86 13

232 10 7

11 82

145 9

24 43 52

157 8

4.2 58.5 34.2 3.8* 3 . 5

25.0 31.5

5 . 4 33.1 5.0

89.2 3.8 2 . 7 4 .2

31.5 55.8 3 . 5 9 .2

16.5 20.0 60.4 3 . 1

* p < .05, when tested as an isolated finding.

as measured by employment status, attitude toward life, view of the future, and psychoso- matic symptomatology.

A slightly greater proportion of cases than controls reported significant disability in re- sponse to the question “Do you have any physical disability which prevents you from doing anything you think you should be able to do?” Those answering affirmatively were asked to estimate the extent of disability from none to total on a five point scale. T h e re- sponses were examined to determine whether the disability reported could be said to be related to breast cancer surgery (e.g. edema of the arm, etc.). It was found that 26 (19%) of the 134 cases reported significant disability; of these, 5 (4% of the total 134) were felt to be related to breast surgery. The controls had 42 (16%) of 260 with significant disability. Thus, the slight increase of disability among cases over the controls could be directly at- tributed to a small but measurable addition of persons disabled by breast surgery.

The subjects were also asked to estimate

their current health status on a five point scale from excellent to very poor. As listed in Table 2, cases and controls were similar in the pro- portion estimating their health as good or excellent. Both groups had similar percentages rating their health as fair. However, cases had a significantly larger proportion of responses in the poor to very poor category.

Current employment status was also felt to be an indirect index of quality of survival since the ability and motivation to hold a job are determined to some extent by the physical and psychological status of the individual. While the differences in employment status were not significant among the three groups, i t is oE interest to note that 31y0 of the cases were currently employed at the time of the survey as compared to 25% of controls. Among formerly employed women, a slightly higher proportion of cases than controls wished to return to work. While not statistically signifi- cant, these differences show no indication of an unsatisfactory adjustment among cases as measured by employment status.

No. 5 SURVIVAL QUALITY IN BREAST CANCER Craig et al. 1455 All subjects were asked to rate themselves

with respect to happiness from a series of six choices ranging from “perfectly happy with life as it is” to “life is not worth living”. As indicated in Table 2, the great majority of both groups rated themselves as happy (either “perfectly happy” or “mostly happy”). How- ever, a slightly higher proportion of cases than controls said they were unhappy.

It was felt that the experience of an illness as serious as breast cancer might have an ef- fect on orientation regarding the future. All subjects were asked to indicate their view of the future from a list of six choices, two of which were considered to be present-oriented (“I never think about the future” and “I live from day to day only”), two future-oriented (“I like to plan ahead’ and “I enjoy anticipat- ing future events”) and two pessimistic re- sponses (“the future can’t be any worse than the present” and “there is no future”). In ad- dition, an open-ended choice was included for those who wished to respond differently from the above choices. As seen in Table 2, cases and controls responded almost identically on this item.

Cases and controls gave similar responses to a series of items designed to elicit the ex- tent of symptoms experienced during the 6 months prior to the survey. The rather lengthy period of 6 months may account for the rela- tively low proportion of both groups report- ing no symptoms.

Virtually identical patterns of recent recrea- tional activities were seen between cases and controls, with 12.7y0 of cases and 10.8y0 of controls reporting participation in sports, while 87.3% of cases and 82.3% of controls reported social activities within the 2 months prior to the survey. Only 10.4y0 of the cases and 11.5% of the controls engaged exclusively in solitary activities during this time.

Responses to the questionnaire were ex- amined to see if they were related to demo- graphic characteristics. Among each of the two groups, cases and controls, age was the only variable that showed significant associa- tions. Disability and ill health increased with age. There was also a significant tendency for younger women to be employed and to show more orientation toward the future and less toward the present.

A significant correlation (p < .001) was seen between the two indices of physical dis- ability, i.e. reports of disability and of ill health for both cases and controls. Among the

indices of psycho-social disability, there was no evidence of significant associations al- though those reporting neutral or negative attitudes toward life also reported a high pre- valence of depression.

In correlating physical with psycho-social ‘disability, the only variables which showed even moderate non-significant association were those of psychiatric symptomatology and view of the future. Thus, for both cases and controls, the physically disabled group re- ported depression and a present orientation more frequently than the non-disabled group.

Deaths among the study group were ascer- tained for a 28-month period after the ques- tionnaire survey. Fifteen of the 134 cases are known to have died during this period, a case fatality rate of ll.2yo. During the same period, 8 or 3.2% of the controls had died. Eight of the 15 cases who died (53.3y0) had reported significant physical disability of the survey questionnaire as compared to 4 of eight controls (50%). Similarly, 13 of the 15 cases (86.7Y0) reported fair, poor, or very poor health, while 7 of the 8 controls (87.5%) fell into this category. Thus, in general, the ma- jority of cases and controls who died during the followup period had characterized them- selves as being in ill health and suffering con- siderable physical disability.

Three of the 15 cases who died (20%) had reported pessimistic attitudes toward life. This becomes of interest when it is recognized that only 5 of the cases in all had reported such an attitude. None of the controls who died had reported pessimistic attitudes. Neither the symptom of depression nor the subjects’ views of the future appeared to be related to mortality.

When the causes of death are examined, it can be seen that breast cancer effectively con- tributed the difference in mortality between cases and controls (Table 3). If these deaths had not occurred, the case population’s mor- tality experience would have been almost the same as that of the controls.

DISCUSSION

Any study based on questionnaires has po- tential limitations related to response rate and validity. In the present study, the pro- portion of subjects who returned the ques- tionnaires seems high enough to make im- portant non-response bias unlikely. It is more

1456 CANCER May 1974 VOl. 33

TABLE 3. Causes of Death for Cases and Controls

Cases Controls Cause of death No. % No. % TOTAL 15 11 2 8 3 1

Generalized cancer 1 Heart disease

Other 2 1

difficult to be certain of the validity of the responses, since it would be virtually impos- sible to validate those relating to psycho- social factors. The internal consistency be- tween responses about physical disability and ill health, and their association with subse- quent mortality lend a certain degree of con- fidence. More important is the fact that the same questionnaire was administered in the same way to both cases and controls. Because there is no reason to believe that the two groups would differ in the accuracy of their responses, the case-control comparisons are likely to reflect any true differences between them.

Two sets of controls were initially selected because it was feared that hospital utilization and indices of disability might be influenced by geographic location. The similarity of the case-control comparisons, whether population or neighborhood controls were used, dispelled this fear. Further, this Ifinding also suggests that geographic factors within the county are not related to breast cancer.

The fact that population and neighborhood controls differed with respect to the propor- tion of women with broken marriages was also a matter for concern, even though a major difference in a single demographic variable could easily have occurred by chance in view of the number of such variables that was in- vestigated. However, extensive internal anal- yses performed on both sets of controls showed that marital status was not related to the dis- ability and attitudinal variables in Table 2, except for view of the future. In this instance, married women gave more future-oriented responses while those with broken marriages tended to be oriented toward the present. However, an adjustment of the data for dif- ferences in marital status, while increasing the proportion of controls oriented toward the future, did not produce differences between cases and controls that were large enough to be statistically significant.

The immediate physical and psychological

Breast cancer 9 1 7 . 5 .’ :: Stroke ;} 3 . 7

effects of the diagnosis and treatment of can- cer in general and of breast cancer in par- ticular have been described elsewhere.1~5~15JO There is no question that these effects are pro- found and, in some cases, devastating for the individual patient during the first months after the surgical procedure of mastectomy. For the breast cancer patient in particular, the real and symbolic meanings of the malig- nancy and its surgical treatment often cause distressing reactions. These not only concern her ability to deal with the presence of a po- tentially life-threatening disease but also her self-perception as a woman and the implica- tions of the cosmetic effects of surgery for her sexual and functional adjustment. In addi- tion, the procedure of radical mastectomy with removal of axillary lymphatic drainage may result in edema of a disabling degree.

The purpose of the present study was not to document the acute effects of breast cancer and mastectomy but to study the long-term quality of survival of patients who had under- gone these experiences. Because the cases in the present study had been diagnosed and treated more than 9 months prior to the sur- vey, it was hoped that they would have reached a stable adjustment with their disease and that their responses would represent an accurate reflection of their long-term quality of sur- vival. In fact, most of the respondents were 5 or more years past diagnosis. The use of a control group was essential in order to esti- mate the degree of disability and malfunction- ing attributable to the cancer and its treat- ment, over and above that resulting from the age and socioeconomic condition of the sub- jects. Thus, the question posed was whether breast cancer patients could be demonstrated to have a significantly inferior quality of sur- vival when compared to women of similar age who had not suffered breast cancer but who were at risk for other causes of disability.

Both of the recent papers which addressed themselves to quality of survival in breast cancer patients were concerned primarily with resumption of usual activities. In the Con- necticut study,T interviews by public health nurses revealed that 83% of the patients had resumed their preoperative responsibilities within 2 years of radical mastectomy, while the Memorial Hospital groupl6 found by means of a mailed questionnaire that 84% of the surviving patients had resumed their pre- operative responsibilities 5 years later. These results are remarkably similar to those from

No. 5 SURVIVAL QUALITY IN BREAST CANCER * Craig et al. 1457 the present study, in which 79% of the women who responded to the question on physical disability and limitation of activity said that they had little or none. T h e corresponding figure of 83% for the control group indicates that little important disability can be at- tributed to the disease or its treatment.

In addition to the use of controls, the pres- ent study extends consideration to psycho- social disability. The Connecticut study re- ported that only 54% of their subjects had a “good’ attitude at initial interview, with 42% “fair” and 4y0 “poor.”7 More disquieting was their finding at the 18-month followup inter- view that the proportion had shifted to 39% good, 57% fair, and 4% poor. Although no comparable question was asked in the present study, the prevalence of psycho-social symp- toms among the cases would be impressive were it not for the fact that the controls showed virtually the same prevalence. The high prevalence of depression and other psy- chosomatic symptoms in both cases and con- trols is related to some extent to the relatively long (6-month) period over which these symp- toms could occur. However, it raises interest- ing questions about the importance of such symptoms, which could be determined best by a prospective study of psychosomatic symp-

tomatology. It would be of interest, for ex- ample, to know what proportion of those re- porting symptoms had experienced distress severe enough to warrant psychiatric atten- tion.

The strong association of physical disability with age was expected. However, with the exception of employment and future orienta- tion, psycho-social disability showed no as- sociation with age. In fact, there was a tend- ency for pessimistic views to be expressed by younger women. Such a trend might be ascribed to their more recent experience with diagnosis and treatment, except that it held true for controls as well as cases.

There was no significant correlation be- tween the indices of physical disability and those of psychosocial disability either among cases or controls. Such a finding suggests that psycho-social disability may be independent of physical disability, except perhaps in ex- treme cases.

In summary, the only important effects of breast cancer seemed to be a slight increase in over-all physical disability by adding a small but measurable number of persons with surgery-related disability and a considerable increase in the death rate during the 28-month followup period.

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