Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancer

Surg Today Jpn J Surg (1995) 25:874-882 @ SURGERYTODAY

© Springer-Verlag 1995

Analysis of the Factors Influencing the Quality of Life of Patients with Advanced or Recurrent Breast Cancer

KOJIRO SHIMOZUMA, 1 HIROSHI SONOO, ~ and KIYOSHI ICHIHARA 2

1 Division of Endocrine Surgery and 2 Department of Clinical Pathology, Kawasaki Medical School, 577 Mastsushima, Kurashiki City, Okayama, 701-01 Japan

Abstract: To investigate the factors influencing the quality of life (QOL) of Japanese patients with advanced or recurrent breast cancer, a newly developed QOL questionnaire, "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (QOL-ACD), was answered by 23 patients, and a multiple regression analysis was performed. The demographic and medical factors relating to the overall QOL score and to the four categories of the QOL-ACD, namely (1) activity, (2) physical condition, (3) psychological condition, and (4) social relationships, were analyzed. The results indicated that skin metastasis, a heavier body weight, and bone metastasis had a strong negative influence on the overall QOL scroe, whereas endocrine therapy, the existence of a primary lesion, and more extensive first surgery had a strong positive influence on it. With regard to the analysis of the four categories, endocrine therapy was found to be positively related to all four categories. The multiple correlation coefficient (R) between the estimated overall QOL score and the observed overall QOL score was about 0.77. The results of this analysis showed that endocrine therapy can improve the QOL of patients with advanced or recurrent breast cancer, and that the QOL-ACD questionnaire could prove extremely useful for predicting the QOL of individual patients and for aiding clinicians in deciding on the most appropriate type of therapy for each patient.

Key Words: quality of life (QOL), breast cancer, endocrine therapy, chemotherapy, multivariate analysis

Introduct ion

The quality of life (QOL) of cancer patients is not usually assessed in a scientific manner, as it is generally thought to be related to personal or subjective attri- butes which are difficult to quantitate. However,

Reprint requests to: K. Shimozuma (Received for publication on May 11, 1994; accepted on July 14, 1995)

we believe that QOL should be considered just as important an endpoint in cancer treatments as the response rate, disease-free survival (DFS), and overall survival (OS), which have generally been regarded as the determinants of cancer treatment efficacy due to the fact that they can be objectively assessed with relative ease.

Since the Karnofsky Performance Status (KPS) score 1 was first developed in 1948, various attempts 1-1° have been made in Western countries to establish QOL measures to assess the important factors making up the overall QOL - - such as physical, psychological, and social aspects. Clinicians in Japan, however, have generally been indifferent to QOL assessment measures, utilizing only the KPS and Eastern Cooperative Oncology Group (ECOG)-PS scores, 7-9 which assess the physical aspect of QOL alone. However, some earnest Japanese researchers al-j3 have recently begun to evaluate the QOL of cancer patients using Japanese translations of the measures developed in Western countries, such as the Functional Living Index for Cancer (FLIC) 2'6 or the European Organization for Research and Treatment of Cancer (EORTC)-QOL questionnaire. 5 In 1993, Kurihara et al. j2'14 developed the first QOL assessment measure for Japanese cancer patients, namely "The QOL Questionnaire for Cancer Patients Treated ~vith Anticancer Drugs" (QOL-ACD, as abbreviated by us with permission from Professor M. Kurihara), the validity and reliability of which were verified during its development. The QOL-ACD was originally designed to reflect the changes in QOL following treatment with anticancer drugs; however, to date, there have been few studies applying the QOL-ACD to cancer patients undergoing various treatment modalities.

Many problems still exist concerning the treatment options for breast cancer, including (a) the choice between breast-conserving treatment and mastectomy for primary therapy; (b) the choice among various

K. Shimozuma et al.: QOL of Patients with Recurrent Breast Cancer 875

postsurgical adjuvant or neoadjuvant (presurgical) therapies; (c) the choice among various therapies such as endocrine therapy, chemotherapy, chemoendocrine therapy, and radiation therapy as intensive treatment for advanced-stage or recurrent cancer patients; and (d) the choice among various treatment modalities including palliative care for relieving pain in patients with far advanced disease or in the terminal stage. When discussing these options, we should consider QOL as one of the major endpoints. In this regard, the latter two problems are discussed herein, while the former two are discussed in other papers. 15,16

In the present study, to investigate the factors associated with the QOL of patients with advanced or recurrent breast cancer, the QOL-ACD questionnaire was answered by 23 patients, following which a multiple regression analysis was performed. The demographic and medical factors relating to the overall QOL score and to the four categories of the ~ O L - A C D , namely , (1) activity, (2) physical condit ion, (3) psychological condit ion, and (4) social relat ionships, were analyzed.

Table 1. Demographic and medical factors possibly affecting the QOL of patients with advanced or recurrent breast cancer

No. of patients (No. of

Factor questionnaires) Result

Time since initial surgery (months) 20 (100) 54-189 (median: 54)

Age 23 (115) 54.4 + 10.5 (mean + SD) Body weight (kg) 16 (91) 56.9 _+ 7.6 (mean + SD) Stage at diagnosis Score a

I 6 (30) 0 II 8 (40) 1 III 3 (15) 2 ~v 3 (15) 3 Unknown 3 (15) -

Performance status (PS) Score 0 20 (99) 2 1 3 (8) 1 2 2 (8) 0

Hospitalization Score Not hospitalized 18 (80) 0 Hospitalized 9 (35) 1

Types of surgery Score None 3 (15) 0 Breast conservation 1 (5) 1 Modified radical mastectomy 12 (60) 2 Radical or extended radical 7 (35) 3

mastectomy

Sites of disease Score Breast (Primary lesion) No/Yes 20 (100)/3 (15) 0/1 Skin No/Yes 20 (100)/3 (15) 0/1 Lymph nodes No/Yes 14 (64)/11 (51) 0/1 Bone No/Yes 12 (60)/11 (55) 0/1 Liver No/Yes 18 (90)/5 (25) 0/1

Types of therapy b Score Chemotherapy No/Yes c 15 (50)/16 (63) 0/1 Endocrine therapy No/Yes c 10 (36)/17 (79) 0/1 Radiotherapy No/Yes d 23 (109)/3 (6) 0/1

QOL, quality of life "Score set for each independent variable for the use of multiple regression analyses b Types of therapy given within 1 month prior to the questionnair c Ten patients who received chemoendocrine therapy (42 questionnaires) were included d One patient who received chemoendocrine therapy (one questionnaire) and one patient who received chemotherapy (one questionnaire) were included

876 K. Shimozuma et al.: QOL of Patients with Recurrent Breast Cancer

Patients and Methods

Recruitment and Characteristics of the Patients

Between February and August, 1993, 25 patients with advanced or recurrent breast cancer who were receiving treatment in our clinic were asked to participate in this study after being informed of its purpose by the authors. The questionnnaires were answered by the patients and returned to us. As two of the patients declined to take part in the study, the total number of subjects was reduced to 23, of whom 3 had primary advanced cancer. All the patients were aware of the fact that they had cancer, and apart from one patient who had not been told about bone metastasis, all were well informed of the treatment they had received, while some had been informed of their prognoses as well. The religious backgrounds of the subjects were obscure and not taken into account, as the majority of Japanese people do not consider themselves to be religious.

The questionnaire was serially answered five times by each of the 23 patients; in principle, every 2 - 4 weeks. Thus, the total number of questionnaires collected was 115. The demographic and medical factors possibly associated with the Q O L of the 23 patients and the scores set for each independent variable for the purpose of multiple regression analyses are listed in Tables 1 and 2. As the performance status (PS), hospitalization, or type of therapy changed in some patients during the course of the study, the questions regarding these aspects were not always answered five times, as shown in Tables 1 and 2. The clinical stage at the first diagnosis of each patient was determined by International Union Against Cancer (UICC) TNM classifications.

Regarding the types of therapy administered within the 1 month prior to the questionnaire, 16 patients received chemotherapy and 17 received endocrine therapy; of these, a total of 10 received chemoendocrine therapy. A total of 23 patients received radiotherapy, which included 1 who was also given chemoendocrine therapy and another who was also given chemotherapy. The drugs given are shown in Table 2.

Questionnaire

The English translation of the QOL-ACD used in this study is shown in Fig. 1. The QOL-ACD is a patient 2 rated QOL evaluation system developed for Japanese cancer patients by a scientific group called "The Research Group For Scientific Assessment Measures of Treatments with Anticancer Drugs" in the Ministry of Health and Welfare in Japan (April 1989 to March

Table 2. Drugs given to the patients with advanced or recurrent breast cancer

Types of therapy

No. of patients (No. of

questionnaires)

Chemotherapy alone 7 (19) Tegafur, Uracil 1 (1) MMC 1 (3) THP-ADM a 1 (2) MIT 2 (3) Ro09-1390 1 (2) CPT-11 1 (2) IO-EdAM 1 (3) CPA + THP-ADM 1 (2) CPA + ADM b + 5FU 1 (2)

Endocrine therapy alone 8 (36) TAM 1 (5) MPA 6 (26) Goserelin acetate 1 (5)

Radiotherapy alone 2 (4) Chemoendocrine therapy 10 (42)

TAM + 5FU + THP-ADM 1 (5) TAM + CPA + ADM + 5FU 1 (5) MPA + CPA 4 (18) MPA + CPA + DFR 1 (1) MPA + CPA + DFR + THP-ADM 1 (1) MPA + DFR 1 (5) MPA + THP-ADM 1 (3) MPA + MIT 1 (3)

Chemoendocrine + Radiotherapy (RT) 1 (1) MPA + THP-ADM + RT 1 (1)

Chemoradiotherapy 1 (1) MIT + RT 1 (1)

None 6 (12)

MMC, mitomycin C; MIT, mitoxantrone; CPA, cyclophospharnide; TAM, tamoxifen; MPA, medroxyprogesterone acetate; DFR, doxifluridine "Pirarubicin b Doxorubicin

1991) and another called "The Research Group for Scientific Assessment of Drug Trea tment" (April 1991 to March 1993), both directed by Professor M. Kurihara.

The QOL-ACD consists of 22 questions, divided i n t o five categories: 6 questions to evaluate activity; 5 to evaluate physical condition; 5 to evalvate psychological condition; 5 to evaluate social relationships; and 1 to. assess the overall aspects of QOL as represented

b ' y a :,face scale, which comprised five faces selected .:~from the 20 faces in the original face scale by Lorish

and Maisiak. 17 Patients are instructed to answer all the questions by circling the number above each scale that best represents their state. The scores for each question are summed tO give an overall score, the minimum being 22 and the maximum, 110, with a higher score representing a better QOL. Mean scores were also


NAME : DATE : / /

AGE : _ _ SEX : 1. MALE 2. FEMALE B.W. : Kg

This questionnaire is being done to help us understand your present state.

Please read the questions and circle the number above the scale which best describes your state durincJ the past several days.

(You r pr ivacy wi l l be strictly protected and there wi l l be no negative influence on your medical treatment, so please answer these questions freely without concern.)

(during the past several days) 1. Have you been able to perform I 2 3 4 5

normal dai ly fe act iv i t es 9 Completely Unable Completely Able

2. Have you been able to go out 1 2 3 4 5

by yourself ? Completely Unable Completely Able

3. Have you been able to go for 1 2 3 4 5 a 30 minute walk ?

Completely Unable Completely Able

4. Has it been hard for you to wa lk 5 4 3 2 f even a short distance? Not At All A Great Deal

5. Have you been able to go up and 1 2 3 4 5 down the stairs? Completely Unable Completely Able

6. Have you been able to take a bath 1 2 3 4 5

by yoursel f ? Completely Unable Completely Able

7. How well have you felt ? 1 2 3 4 5

Extremely Poor Extremely Well

8 Have you had a good appet i te? 1 2 3 4 5

Extremely Poor Extremely Good

9. Have you enjoyed your meals ? I 2 3 4 5

Not At All A Great Deal

10. Have you experienced vom i t i ng? 5 4 3 2 1

Not At All Very Often

1 1 Have you lost we igh t ? 5 4 3 2 1


12. Have you slept we l l ? 1 2 3 4 5

Not At All Extremely Well

(during the past several days) 13. Have you been absorbed in anything?

14. Have you coped well w i t h everyday stress ?

15. Do you feel unable to concentrate ?

16. Are you encouraged by anyone or anything ( family, friends, religion, hobbies, e tc . )?

, ~ ? 4 5


I 2 4 5

Not At AI~ Extremely Well

5 4 2 1


1 2 4


17. Have you felt ill at ease about the condition of your disease?

18. Have you felt unwi l l ing to meet anyone other than your fami ly?

19. How much trouble do you feel you give

your fami ly over your medical treatment ?

20. Are you anxious about your social life in the fu tu re?

21. Are you worr ied about the medical costs of your t reatment ?

22.

5 4 2

Not At All A G~eat Deal

5 4 2


5 4 2

None A Great Deal

5 4 2

Not At AI$ A Great Deal

5 4 2


Please circle the number of the face expressing your state during the past several davY.

5 4 3 2 1

~ A t last, please confirm that you have answered all of the questions.

[ A column filled out by doctors or nurses]

a. 1 . inpat ient 2. outpat ient I e. Remarks :

I b. P.S :

c, B , W . : _ _ Kg

d. Date : / / Recorder :

Fig. 1. "The QOL Questionnaire for Cancer Patients Treated with Anticancer Drugs" (English translation)

calculated for the four categories apart from that evaluating the global QOL by the face scale. Each score ranged from one to five.

Data Collection and Management

Compliance with completion of the QOL-ACD in this study was 93.9%. Questionnaires with no more than 2 of the total 22 questions unanswered were judged to be valid. Any missing scores due to unanswered questions were substituted with the mean score for the remaining questions. According to this criterion, all of the 115 questionnaires were valid (100%).

Statistical Methods

The factors associated with QOL were evaluated by a multiple regression analysis. The overall QOL score was set as a dependent variable and the following factors were set as independent variables: age, body weight, clinical stage at the initial diagnosis, PS, hospitalization, types of surgery, sites of disease, and types of therapy given within 1 month prior to the questionnaire (Table 1). For the multiple regression analyses, we set the score for each independent variable as indicated in Table 1. In analyzing the factors that were related to each of the four categories of the

QOL-ACD, the mean score of each category was set as a dependent variable. Lotus 1-2-3 (Lotus Develop- ment, Cambridge, USA) was used for the accumulation of data and calculation of the score. The statistical analyses including the multivariate analyses were carried out by general-purpose statistical software, Stat Flex (View Flex, Tokyo, Japan).

Results

Factors Associated with the Overall QOL Score

The results of the multiple regression analysis after stepwise selection of the variables are shown in Table 3. :It was revealed that skin metastasis, a heavier body ~eight, and bone metastasis had a strong negative i.n~uence on the overall QOL score (P < 0.00.!), while etid~crine therapy, the existence of a primary lesion, a~d'more extensive first surgery had a strong ipositive influence (P < 0.001). The stage at initial diagnosis and~'libspitalization had a significant but ngt strong negative influence (P < 0.005), while PS had a positive influence (P < 0.01). The multiple correlation coefficient (R) between the estimated overall QOE' gcore . and the observed overall QOL score was 0.766~:(p= o.oooo).


Table 3. Multiple regression analysis of the factors associated with the overal QOL score of patients with advanced or recurrent breast cancer

Regression Factor coefficient Standard error t value P value

Skin metastasis -33.880 5.62304 6 .025 0.0000"** Body weight -0.3177 0.06163 5 .155 0.0000"** Endocrine therapy 11.850 2.89460 4.094 0.0001"** Primary lesion 12.666 12.6656 3.755 0.0003*** Types of surgery 9.7957 2,85473 3.431 0.0009*** Bone metastasis -12.102 3.58546 3 .375 0.0010"** Stage at diagnosis -7.6546 2.42104 3 .162 0.0021"* Hospitalization - 9.4996 3.11061 3 .054 0.0029" * PS 6.1856 2.20592 2 .804 0.0060* Chemotherapy 3.6017 2.22431 1.619 0.1084

PS, performance status *P < 0.01; **P < 0.005; ***P < 0.001 All the results of the multiple regression analysis were those obtained after stepwise selection of the variables R (multiple correlation coefficient) = 0.7666 (P = 0.0000)

Factors Associated with the Mean Score of Each of the Four Categories of the QOL-ACD

The results of the multiple regression analyses for the four categories after stepwise selection are shown in Table 4. Endocrine therapy had a strong positive influence on all four categories (P < 0.001); skin metastasis had strong negative inflluence on all of the categories except "social relationships" (P < 0.001); a heavier body weight had a strong negative influence on "activity" (P < 0.001); PS had a strong positive influence on "activity" (P < 0.001); bone metastasis had a strong negative influence on "physical condition" (P < 0.001); chemotherapy had a strong positive influence on "psychological condition" (P < 0.001); and age had a strong positive influence on "social relationships" (P < 0.001).

Discussion

Breast cancer is moderately sensitive to a variety of treatment modalities such as endocrine therapy, chemotherapy, radiation therapy, and their various combinations. However, considering the fact that patients undergoing intensive anticancer therapy often experience such severe side effects as myelosuppres- sion, alopecia, nausea and vomiting, diarrhea, stomatitis, and irreversible nerve damage, these therapies may not always improve QOL even when they do result in prolonging the DFS or OS. On the other hand, some types of therapy, especially endocrine therapy or mild chemotherapy using orally administered antimetabolites, can improve a patient's condition, even though their efficacy with regard to the disease

itself may be poor. Thus, the endpoints for cancer treatments should not be limited to the response rate, DFS, or OS, but should also include QOL, and for this purpose we need to develop an optimal method to evaluate the OOL of cancer patients in a more scientific manner.

The QOL score should provide clinicians and patients with clinically relevant information in daily care. It should also (a) define the superiority of various treatment options, especially when their is indecision in choosing among options whose response rate, DFS, or OS are known to be similar; and (b) be able to predict future QOL, especially after the results of a prospective study revealing the potential factors associated with the QOL have become available.

Although many measurements have been developed for evaluating the QOL specific to cancer patients in Western countries, 3'4'1° there has been no "gold standard" for measuring QOL. 18 There are a number of problems with the QOL systems of measurement currently in use, including (a) whether or not the patient is aware of their cancer and/or prognosis, (b) the patient's age, (c) the validity of applying a single QOL measurement to people from different cultures and speaking different languages, (d) the choice between a patient-rated and a health professional- rated questionnaire, and (e) poor compliance with completion of the evaluations.

In considering these problems surrounding the systems of measurement of QOL:

1. Most of the systems from Western countries have been devised on the premise that the patients have been notified of their cancer. However, in Japan, most cancer patients are not told that they have

K. Shimozuma et al.: QOL of Patients with Recurrent Breast Cancer

Table 4. Multiple regression analysis of the factors associated with the four categories of the QOL-ACD score of patients with advanced or recurrent breast cancer

Regression Factor coefficient Standard error t value P value

Activity a Skin metastasis -1.8737 0.25783 7.267 0.0000"*** Body weight -0.0139 2.816E-3 4.923 0.0000"*** PS 0.6170 0.17430 4.491 0.0000"*** Endocrine therapy 0.6027 0.17208 3.502 0.0007**** Liver metastasis -0.4524 0.16761 2.699 0.0081"* Hospitalization -0.4455 0.17430 2.556 0.0120" Bone metastasis -0.4167 0.16545 2.519 0.0133" Lymph node metastasis -0.3581 0.14800 2.419 0.0173" Stage at diagnosis -0.0973 0.06736 1.444 0.1518

Physical condition b Endocrine therapy 0.8280 0.12216 6.778 0.0000'*** Skin metastasis -1.1807 0.25580 4.616 0.0000'*** Bone metastasis -0.6259 0.15666 3.995 0.0001"*** Hospitalization -0.4072 0.14115 2.885 0.0048*** Body weight -7.92E-3 2.763E-3 2.868 0.0050*** Primary lesion 1.6043 0.56238 2.853 0.0052** Types of surgery 0.3560 0.13105 2.716 0.0077** Stage at diagnosis -0.2434 0,10707 2.274 0.0250* Radiotherapy 0.3320 0.22175 1.497 0.1374

Psychological condition c Skin metastasis -0.9419 0.21254 4.431. 0.0000"*** Endocrine therapy 0.4347 0.12347 3.521. 0.0006**** Chemotherapy 0.3898 0.11497 3.391 0.0010"*** Body weight -8.77E-3 2.813E-3 3.116 0,0024*** Primary lesion 1.1953 0.43654 2.738 0.0073** Types of surgery 0.2385 0.10897 2.188 0.0308* PS 0.2319 0.11301 2.052 0.0426* Stage at diagnosis -0.1272 0.09306 1.367 0.1745

Social relationships d Endocrine therapy 0.6962 0.15753 2.420 0.0000"*** Age 0.0321 7.619E-3 4.207 0.0001"*** Body weight -0.0126 3.759E-3 3.355 0.0011"** Lymph node metastasis 0.5278 0.16436 3.211 0.0017"** Skin metastasis -0.9094 0.28642 3.175 0.0020*** Primary lesion 0.8498 0.43230 1.966 0.0520 Chemotherapy 0.2893 0.16325 1.772 0.0793 Stage at diagnosis -0.0999 0.13473 0.742 0.4598

*P < 0.05; **P < 0.01; ***P < 0.05; ****P < 0.001 All the results of the multiple regression analysis were those obtained after stepwise selection of the variables aR (multiple correlation coefficient) = 0.8046 (P = 0.0) bR = 0.7514 (P = 0.0) ce = 0.6492 (P = 0.0) dR = 0.6339 (P = 0.0)

879

cancer, despite the recent revelation that 88% of experimentally notified patients with breast cancer approved of the act of notification.19

2. A positive relationship between age and QOL has been reported. 2°-24

3. In a field study using the E O R T C core questionnaire, Aaronson et al. 25 tried to determine the influence of cultural backgrounds among people in southern and northern European countries and Japan. They found a difference in the psychometric

properties of the questionnaire between the European and Japanese people. In our experience using a Japanese version of the FLIC score, the linear analogue scale for each question was occasionally misunderstood by Japanese patients; in other words, the percentage of patients who could correctly answer the questionnaire was 83.1%. 11

4. The majority of investigators currently agree that a patient-rated questionnaire is better than a


doctor-, nurse-or other health professional-rated questionnaire. 26

5. Finkelstein et al. 27 reported in the study of an assessment of QOL for metastatic lung cancer patients using FLIC that 83% of the patients com- pleted the instrument after 1 month, but by 6 months, compliance with completion had declined to only 33%.

The QOL-ACD was developed in an attempt to eliminate the above five problems surrounding the systems of measurement currently in use in Western countries. Instead of making a slash on the scale, patients are instructed to answer each question by circling the number (1 to 5) above the scale in the QOL-ACD. In the present study, 23 out of 25 eligible patients agreed to participate, and compliance with completion of the instrument was high at 93.9%, indicating that the QOL-ACD was easier for Japanese breast cancer patients to answer than the Japanese version of the FLIC.

It is noteworthy that this study revealed an apparent discrepancy between our impression of the gravity of the patients' status and the results of the regression analysis which revealed factors associated with the actual impression of the patients about their own status. Interestingly, the patients with skin metastasis suffered poor QOL although we would not have considered their condition as severe, because skin lesions do not usually tend to be fatal in the near future. However, this result suggested that we should put more emphasis on the therapy of patients with skin metastasis. Conversely, liver metastasis had no significant influence on the overall QOL score, although it had a weakly negative relationship only to "activity." We tend to consider the condition of patients with liver metastasis as severe because of its potentially poor prognosis, 28 and recommend that those patients be admitted to hospital for intensive therapy, even when they have no symptoms. However, these results suggest that we may be better off treating patients with liver metastasis on an outpatient basis rather than affecting their QOL by hospitalization. The fact that bone metastasis had a strongly negative influence on the overall QOL score and an apparent relationship to "activity" and "physical condition" was understand- able, since patients with bone metastasis sometimes suffer severe pain and gait disturbance.

The positive relationship between the overall QOL score and the existence of a primary lesion is difficult to interpret because we tend to think that most patients are willing to have their primary breast lesion dis- sected. This result might be attributed to the possibility that these patients had not experienced any trouble caused by surgery, or perhaps that they just did not

realize the severity of their condition even if they had life-threatening metastatic lesions. It is also difficult to interpret the significant association between the QOL score and the various types of initial surgery. As the time-points when the questionnaires were distributed in this study were a considerable period after the patients' initial surgery (median, 54 months), it is unlikely that the types of surgery had any influence on the QOL of the patients. Our previous analysis using the QOL-ACD of the breast cancer patients within 2 years after surgery revealed that there were no differ- ences in the overall QOL scores between the patients who received breast-conserving treatment (BCT) and modified radical mastectomy (MRM) during any period of the study, although MRM was superior to BCT with respect to the mean score of "psychological condition". 16 However, we have no available data on the relationship between the surgical procedure and the QOL of the patients 3 or more years after surgery. Thus, the precise relationship between QOL and the type of surgery is still a matter of controversy among investigators .24,29

Interestingly, a heavier body weight had a strong negative influence on the overall QOL score and "activity" in this study. During the development of the QOL-ACD, we assumed that a loss of body weight would have a negative influence on the QOL of patients, since it usually implies a poor prognosis for patients with cancer. However, this result may only reflect the fact that most women feel more comfortable with less body weight. Therefore, further investigation as to the actual relationship between QOL score and the fluctuation of body weight before and after therapy needs to be conducted.

Regarding the treatment modality, endocrine therapy had a strong positive influence on the QOL score, while chemotherapy had a positive association with "psychological condition." The analysis using a different set of independent variables for the therapies of chemotherapy alone, endocrine therapy alone, and chemoendocrine therapy demonstrated that the factor of "chemoendocrine therapy" had a more positive influence on the QOL score than "endocrine therapy alone," and that "chemotherapy alone" did not have a significant influence, but rather a weak negative influence on "physical condition" (data not shown in this paper). The results of this study reflect the following facts: (a) The administration of tamoxifen (TAM) does not usually affect the patient's condition. (b) High-dose medroxyprogesterone acetate "(MPA) sometimes relieves the pain experienced by patients with bone metastasis, increases their appetite, makes them feel comfortable, and reduces the adverse effects of chemotherapy, such as nausea, vomiting, and bone marrow suppression, which decrease compliance with


chemotherapy. These advantages of MPA might be attributable to the corticosteroid-like or anabolic effects of MPA, 3° although the actual mechanisms are not well understood.

Pozo et al. 24 revealed in their study of the relationship between types of surgery and emotional adjustment to breast cancer that TAM therapy was not associated with any measure of well-being, whereas chemotherapy resulted in postsurgical distress, was inversely related to life satisfaction and self-ratings of adjustment, and was positively related to thought intrusion and the ratings of pain interfering with daily activities.

The relationship between the efficacy of a therapy and the QOL score is of great concern to us. In fact, in a previous study I 1 we reported a significantly positive relationship between these factors using another QOL measure, the FLIC. Since the design of the present study did not allow us to investigate this issue, we are planning it in the next study using the QOL-ACD.

As the multiple correlation coefficient between the estimated overall QOL score and the observed overall QOL score was high in this study, the expected QOL calculated from the regression equations may serve as a predictor of Q O L for patients with breast cancer in a similar setting. The findings of this study led to the conclusions that endocrine therapy can improve the QOL of patients with advanced or recurrent breast cancer, and that the QOL-ACD will be useful for selecting the most appropriate type of therapy and predicting of the QOL of individual patients.

Acknowldgments. We wish to express our gratitude to Prof. M. Kurihara of Showa University and Prof. emeritus K. Sarai of Hiroshima University for their valuable advice.

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Analysis of the factors influencing the quality of life of patients with advanced or recurrent breast cancer