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Quality-of-Life Scores Predict Outcome in Metastatic but Not Early Breast Cancer

From the Australian Cancer Society and Australian New Zealand Breast Cancer Trials Group, University of Sydney, Sydney, Australia; Bürgerspital, St Gallen; International Breast Cancer Study Group Coordinating Center, Bern, Switzerland; International Breast Cancer Study Group Statistical Center, Dana-Farber Cancer Institute, Boston, MA; and Oncology Institute of Southern Switzerland and European Institute of Oncology, Milan, Italy.

Address reprint requests to Alan Coates, MD, FRACP, Australian Cancer Society, GPO Box 4708, Sydney NSW 2001, Australia; email alancoates{at}cancer.org.au

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: We compared the prognostic value of quality-of-life (QL) scores in the adjuvant setting and after relapse in two randomized trials of the International Breast Cancer Study Group.

PATIENTS AND METHODS: More than 2,000 premenopausal and postmenopausal patients with node-positive breast cancer who were participating in randomized trials that compared adjuvant therapies completed QL assessments for physical well-being, mood, appetite, and coping at study entry and at months 3 and 18 if they remained relapse-free and, in case of relapse, at 1 month and at 6 months after relapse. Cox regression models were used to test the relationship between QL scores and disease-free survival (DFS), in the adjuvant setting, or overall survival, in the case of postrelapse QL measurement. All models were stratified by language/country group and included other factors related to QL and/or outcome.

RESULTS: DFS was not significantly predicted by QL scores at baseline or month 18, or by changes in QL score between baseline and months 3 or 18. In contrast, after relapse, QL scores were predictive for subsequent overall survival. One month after relapse, better mood (P = .04) in premenopausal patients and better appetite (P = .005) in postmenopausal patients were associated with longer survival. Six months after relapse, better physical well-being (P = .03) and appetite (P = .03) in premenopausal patients and better physical well-being (P < .0001), mood (P = .002), appetite (P = .0001), and coping (P = .0001) in postmenopausal patients predicted longer survival.

CONCLUSION: Any prognostic significance of QL scores in the adjuvant setting is minimal or obscured by chemotherapy effects, but there is strong prognostic significance of QL scores after disease relapse. The contrast suggests that patient perception of the severity of underlying illness may determine reported QL scores.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
QUALITY OF LIFE (QL) is an important consideration in treatment of breast cancer. Patient self-assessment of QL is an established end point for treatment comparisons.^1,2 QL scores are also independent prognostic factors for survival duration in metastatic breast and other cancers.^3-6

The reason for this association is uncertain. It might merely reflect patients’ perception of the severity of underlying disease. Alternatively, there could be a true causative relationship whereby perception of better QL prolongs survival. If so, QL scores should also be prognostic among patients with early stages of disease. Since the landmark observation by Greer et al⁷ two decades ago that patients with fighting spirit or active denial did better than those with stoic acceptance or feeling helpless/hopeless, the prognostic relevance of psychosocial factors has been debated within and outside the medical community. Many patients are challenged by a perceived social requirement for positive thinking. They may feel devastated and even fear doing harm to their health when they experience a normal grief reaction after diagnosis. In a recent replication, no survival difference could be found by comparing different types of psychological response.⁸ However, patients with higher helplessness/hopelessness scores had a reduced disease-free survival (DFS). Clarification of these issues may assist patients’ subjective adjustment.

The International Breast Cancer Study Group (IBCSG) has included QL assessment in adjuvant therapy trials since 1986.⁹ We now report the association between outcome and QL scores recorded in the adjuvant setting and after disease relapse in pre- and postmenopausal patients with node-positive breast cancer.

	PATIENTS AND METHODS

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Trials
Between July 1986 and April 1993, two IBCSG trials examined similar questions of timing and duration of adjuvant cytotoxic therapy for patients with node-positive operable breast cancer. In Trial VI, we randomized 1,475 eligible premenopausal and perimenopausal patients in a two by two factorial design to receive three or six initial cycles of chemotherapy using oral cyclophosphamide, intravenous methotrexate, and fluorouracil (CMF), with or without three later single cycles of reintroduction CMF administered at 3-month intervals.¹⁰ At the same time, 1,212 eligible postmenopausal node-positive patients were randomized in another two by two factorial study, IBCSG Trial VII.¹¹ All postmenopausal patients received 20 mg of tamoxifen daily for 5 years. Tamoxifen alone was compared with tamoxifen combined with either three early cycles of CMF, the delayed introduction of three single CMF cycles at months 6, 9, and 12, or both early and delayed CMF.¹¹

QL was measured using four linear analog self-assessment (LASA) indicators of components of QL previously shown to be affected by breast cancer and chemotherapy or chemo-endocrine therapy. Each LASA indicator consisted of a 10-cm line anchored at both ends with words describing the minimal and maximal extremes of the dimension being measured. Physical well-being (from "good" to "lousy"), mood (from "happy" to "miserable"),^12,13 and coping/perceived adjustment (responding to the question "How much effort does it cost you to cope with your illness?" from "no effort at all" to "a great deal of effort") (Perceived Adjustment to Chronic Illness Scale [PACIS]¹⁴) were assessed as global indicators; appetite (from "good" to "none") was included as a specific indicator for side effects. Responses on the global indicators are expected to reflect the summation of the individual meaning and importance of various disease- and treatment-related factors for each patient.¹⁵ Concurrent validity,¹⁶ test-retest reliability,¹⁷ and responsiveness to chemotherapy¹⁸ have been documented previously. Their relevance for treatment comparisons has been shown in both the adjuvant⁹ and the advanced disease settings.² Finally, their sensitivity to disease recurrence⁹ and, in advanced disease, to performance status¹⁹ and tumor response,²⁰ and their prognostic value for survival^3,5 have been demonstrated. QL forms were translated into the seven required main languages by professional translators, pilot-tested by physicians and patients in the relevant centers, and adjusted in the light of their feedback to ensure not only linguistic, but also conceptual equivalence. The LASA translations were further checked by an independent forward-backward translation procedure. The time frame of the indicators was related to the period since the last full clinical assessment. Patients were asked to complete QL assessments at regular intervals for 6 years after randomization or until relapse, whichever occurred first, and at 1 and 6 months after disease relapse, in the latter case.

For the primary hypothesis, that QL scores in the adjuvant setting are prognostic, we used the scores at the start of adjuvant treatment (ie, the baseline assessment). Further exploratory analyses included the scores at 18 months (ie, after completing chemotherapy in all treatment arms), the change in QL scores from baseline to month 3 as a measure of early psychological adaptation,⁷ and the change in QL scores from baseline to month 18 as a measure of adaptation in the adjuvant phase.⁹ In addition, for confirmatory analysis³ of those factors previously shown to be prognostic in advanced disease, we used the scores at 1 and 6 months after disease relapse.

Statistical Methods
The LASA scores ranged from 0 to 100, with higher numbers reflecting better QL. To be consistent with prior analyses of these data, analyses were carried out using a square root transformation of these scores.^9,15 Cox regression models²¹ were used to test the relationship between QL scores and outcome (DFS and overall survival). Relative risks were calculated using the estimated parameters from these models and represent the effect of a change of one unit of QL in the square root scale. DFS was measured from the date of randomization. In the analysis of QL after relapse, time to death (from any cause) or censoring was measured from the date of the QL assessment. We previously showed that language/culture had a significant influence on the QL scores obtained. Therefore, all analyses were stratified by culture, which was defined by language/country groupings.²² The analysis of QL in the adjuvant setting included as covariates the number of positive nodes (one to three v four or more), estrogen receptor status, and assigned treatment. The analysis of QL after relapse included as covariates age, disease-free interval ( 2 v > 2 years), and site of relapse (local/regional v bone v other distant). The cutoff for significance was set at P = .05, and no adjustment was made for multiple comparisons; two-sided P values are presented as descriptive statistics to illustrate associations in the observed results.

Logistic regression was used to test for factors possibly predictive of whether QL assessments were completed. Analysis of variance was used to test for associations between QL measures and these factors.

	RESULTS

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Description of the Sample
Baseline QL forms were completed by 1,262 (86%) of the 1,475 Trial VI patients and by 1,008 (83%) of the 1,212 Trial VII patients.²² Because analyses were stratified by culture, 50 patients from four countries who did not complete the QL form in a primary language of their region were excluded from the analyses (31 from Trial VI, 19 from Trial VII).

At 18 months, 1,262 Trial VI patients and 1,019 Trial VII patients remained disease-free. QL forms were completed at month 18 by 869 (69%) of these Trial VI patients and by 742 (73%) of these Trial VII patients. Excluded from the month 18 analysis were 44 patients who did not complete the QL form in a primary language of their region (24 from Trial VI, 20 from Trial VII). For the analysis of changes from baseline to month 3, there were 983 assessable Trial VI cases and 737 assessable Trial VII cases; for the analysis of changes from baseline to month 18 there were 763 assessable Trial VI cases and 630 assessable Trial VII cases.

After a 7-year median follow-up, relapses had been reported for 715 Trial VI patients and 568 Trial VII patients. At month 1 after relapse, 682 Trial VI and 502 Trial VII patients were alive to complete a QL assessment; of these, 203 Trial VI patients (30%) and 149 Trial VII patients (30%) actually completed the assessment. At month 6 after relapse, 603 Trial VI and 426 Trial VII patients were alive to complete a QL assessment; of these, 219 Trial VI patients (36%) and 162 Trial VII patients (37%) actually completed the assessment. Patients who did not complete the QL form in a primary language of their region were excluded from the analyses: at month 1, eight from Trial VI and three from Trial VII; at month 6, nine from Trial VI and five from Trial VII. The interquartile range of the times from relapse to QL assessment were 2 to 8 weeks for the month 1 assessment and 22 to 30 weeks for the month 6 assessment.

Prognostic Relevance of QL in the Adjuvant Setting
None of the baseline QL indicators showed a statistically significant relationship with DFS, as listed in Table 1. Similar results were obtained within each of the five largest cultural groups and within the group of patients who completed the baseline QL assessment on day 1 of cycle 1. Representative DFS curves according to baseline mood score (0 to 50 v 51 to 85 v 86 to 100) for each trial are shown in Fig 1a and b. Similarly, no significant prediction of DFS was provided by month 18 QL scores or by change in QL scores from baseline to month 3 or baseline to month 18.

View larger version (23K): [in this window] [in a new window]   Fig 1. (a) DFS according to baseline mood score, Trial VI (premenopausal). (b) DFS according to baseline mood score, Trial VII (postmenopausal). (c) Overall survival according to month 1 postrelapse mood score, Trial VI (premenopausal). (d) Overall survival according to month 1 postrelapse mood score, Trial VII (postmenopausal). (e) Overall survival according to month 6 postrelapse mood score, Trial VI (premenopausal). (f) Overall survival according to month 6 postrelapse mood score, Trial VII (postmenopausal).

Prognostic Relevance of Postrelapse QL
Results after disease relapse were strikingly different. Tables 2 and 3 display the results of the Cox regression analyses of the prognostic relevance of the month 1 and month 6 QL scores on overall survival. At month 1, mood was significantly prognostic in Trial VI, as was appetite in Trial VII. At month 6, all of the QL scores were significantly prognostic, except mood and PACIS in Trial VI. Representative overall survival curves according to month 1 and month 6 postrelapse mood scores for each trial are shown in Fig 1c to 1f.

QL form submission rates varied considerably among participating institutions, and the differences among countries were statistically significant. Submission rates decreased considerably with increasing disease-free interval, ranging from 47% for failures during the first year to 11% for failures in year 7 and beyond. However, QL scores after relapse did not vary according to disease-free interval. There was some variation in submission rates according to site of relapse, but the pattern was not consistent. QL scores did vary according to site of relapse, with higher scores for local/regional failures than for distant failures. Neither submission rates nor QL scores varied significantly by patient’s age. The women who completed their postrelapse QL assessments had somewhat higher baseline mood scores. However, even among those cases who relapsed, there was no significant relationship between baseline QL scores and DFS.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
We found a marked difference between the lack of prognostic value of QL scores at the time of adjuvant treatment of women with node-positive breast cancer (ie, primary hypothesis) and the strong prognostic value of those obtained using the same QL measures after disease relapse (ie, confirmatory analysis³ ). In the adjuvant setting, either at the start of or after completing adjuvant chemotherapy, the QL indicators did not predict DFS. Patients’ adaptation, measured by the improvement in QL scores over the first 3 or 18 months, was also unrelated to outcome.

In contrast, after relapse, QL scores did predict subsequent survival, even after controlling for appropriate covariates. The hazards ratios reported in Tables 1 to 3 represent a relatively large clinical change. For example, these ratios represent approximately twice the magnitude of the effect on mood of starting delayed adjuvant chemotherapy for postmenopausal patients who were chemotherapy-naïve until 9 months after diagnosis.⁹ The QL scores recorded 6 months after relapse were more clearly prognostic than those recorded 1 month after relapse. This difference may reflect the further evolution of metastatic disease in the interval, with emergence of more specific disease-related symptoms that affect QL. In particular, QL scores 6 months after relapse may reflect the impact of tumor response or progression after treatment for recurrent disease. As shown for the same QL indicators in patients with second-line endocrine treatment, the difference in changes by the type of tumor response were not obvious within the first month of treatment for advanced disease but became substantial in the subsequent months.²⁰ Alternatively or in addition, the scores recorded 1 month after relapse may have been more affected by further factors that added noise to an underlying prognostic signal, such as the heterogeneous acute emotional reactions to the recent diagnosis of relapse and the impact of diagnostic procedures and treatment for advanced disease.

The lack of prognostic significance of QL scores in the adjuvant setting could not be attributed to an insensitivity of the measures or to the variety of languages and cultures involved, because QL scores obtained after disease relapse with the same measures in the same populations were strongly prognostic for subsequent survival. The large sample size argues against a simple lack of statistical power, especially as significant associations were seen with smaller numbers in this and other studies of patients with metastatic disease. Previous validation studies have shown that these QL indicators have good concurrent validity.^13,16

Some patients may feel devastated or fear that they may be doing harm to their health when they experience a normal grief reaction after diagnosis. The lack of prognostic association of early adjustment in our study may assist clinicians in reassuring such patients.

Previous studies have shown that QL scores in patients with metastatic breast and other cancers are clearly associated with subsequent survival duration, even in studies that present multivariate models after allowance for other known prognostic factors.^3,4,6,23-28 The mechanism that underlies this relationship remains uncertain. One explanation is that the patient is aware of the severity of the underlying illness to an extent not captured by conventional medical prognostic factors and that this perception affects QL self-reporting in such a way that patients with worse underlying disease report worse QL.³

Another possibility equally compatible with the data from metastatic disease studies is that the perception of better QL positively influences survival duration, an explanation supported by intervention studies.^29-32 If this hypothesis were true, it might have been expected that similar positive influences at an earlier stage of the disease would confer a DFS advantage in the adjuvant setting. Such an advantage was not observed in the current study.

The hypothesis that psychosocial factors are prognostic in patients with early breast cancer has been studied extensively. As reviewed elsewhere,^33-36 the lack of conclusive evidence in either direction is mainly a result of methodologic shortcomings in relatively small cohorts, especially insufficient control for biomedical or behavioral risk factors. In addition, there is a heterogeneity of concepts. The majority of these studies investigated more specific concepts (eg, mental adjustment) in greater detail than did our assessment by QL indicators.

Our findings are consistent with those of a similar study in which psychological symptoms were assessed before chemotherapy in 280 patients with stage II breast cancer over a 15-year period. There was no evidence that the level of initial distress was predictive of subsequent DFS or overall survival.³⁷ Together, these support the hypothesis that accurate patient perception of the severity of underlying illness influences the QL scores reported.³

In contrast, in the replication of the Greer study, a higher helplessness/hopelessness score had a moderate detrimental effect on 5-year DFS in 578 patients with stage I or II breast cancer.⁸ This finding points again to the hypothesis that coping has an impact on survival, although to a narrow spectrum of psychological response only. It is also compatible with a third explanation, that QL scores are indicative for patients’ adherence to treatment and follow-up schedules and, thereby, are related indirectly to the disease process.

There is an indication in our data that adjuvant chemotherapy may have a confounding effect. In the subgroup of patients assigned no early chemotherapy, less effort to cope was weakly associated with increased risk of relapse. Although QL effects on DFS may be obscured by the effects of chemotherapy, any prognostic significance of QL scores in this subgroup is modest compared with the significance of QL scores after relapse. Furthermore, the association is in the opposite direction after relapse, with less effort to cope associated with decreased risk of relapse. The reason for this difference is unclear and requires further prospective investigation.

In summary, any prognostic significance of QL scores is minimal or obscured by chemotherapy effects in the adjuvant setting but is substantial in advanced disease. The contrast suggests that patient perception of the severity of underlying illness may determine reported QL scores. Our findings do not mean that there is no need for psychosocial interventions in patients with early breast cancer. They suggest, however, that the primary objective of such interventions is improvement of patients’ QL and not prolongation of survival.

	ACKNOWLEDGMENTS

 
Supported by the Ludwig Institute for Cancer Research, Cancer League of Ticino, Swiss Cancer League, Swedish Cancer League, Australian Cancer Society, Australian New Zealand Breast Cancer Trials Group (NHMRC grants no. 880513 and 910420), Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, United States National Cancer Institute (grant no. CA-75362), and American Cancer Society (grant no. RPG-90-013-08-PBP).

We thank the patients, physicians, nurses, and data managers who participate in the International Breast Cancer Study Group trials, especially Rita Hinkle, for meticulous data management.

	REFERENCES

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1. Priestman TJ, Baum M: Evaluation of quality of life in patients receiving treatment for advanced breast cancer. Lancet 1: 899-901, 1976[Medline]

2. Coates AS, Gebski V, Bishop JF, et al: Improving the quality of life in advanced breast cancer. A comparison of continuous and intermittent treatment strategies. N Engl J Med 317: 1490-1495, 1987[Abstract]

3. Coates AS, Gebski V, Signorini D, et al: Prognostic value of quality-of-life scores during chemotherapy for advanced breast cancer. Australian New Zealand Breast Cancer Trials Group. J Clin Oncol 10: 1833-1838, 1992[Abstract]

4. Ganz PA, Lee JJ, Siau J: Quality of life assessment. An independent prognostic variable for survival in lung cancer. Cancer 67: 3131-3135, 1991[Medline]

5. Coates AS, Thomson D, McLeod GR, et al: Prognostic value of quality of life scores in a trial of chemotherapy with or without interferon in patients with metastatic melanoma. Eur J Cancer 29A: 1731-1734, 1993

6. Faller H, Bulzebruck H, Drings P, et al: Coping, distress, and survival among patients with lung cancer. Arch Gen Psychiatry 56: 756-762, 1999[Abstract/Free Full Text]

7. Greer S, Morris T, Pettingale KW: Psychological response to breast cancer: Effect on outcome. Lancet 2: 785-787, 1979[Medline]

8. Watson M, Haviland JS, Greer S, et al: Influence of psychological response on survival in breast cancer: A population-based cohort study. Lancet 354: 1331-1336, 1999[Medline]

9. Hürny C, Bernhard J, Coates AS, et al: Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer. Lancet 347: 1279-1284, 1996[Medline]

10. International Breast Cancer Study Group: Duration and reintroduction of adjuvant chemotherapy for node-positive premenopausal breast cancer patients. J Clin Oncol 14: 1885-1893, 1996[Abstract/Free Full Text]

11. International Breast Cancer Study Group: Effectiveness of adjuvant chemotherapy in combination with tamoxifen for node-positive postmenopausal breast cancer patients. J Clin Oncol 15: 1385-1394, 1997[Abstract]

12. Priestman TJ, Baum M, Jones V, et al: Comparative trial of endocrine versus cytotoxic treatment in advanced breast cancer. BMJ 1: 1248-1250, 1977

13. Hürny C, Bernhard J, Coates AS, et al: Responsiveness of a single-item indicator versus a multi-item scale: Assessment of emotional wellbeing in an international breast cancer trial. Med Care 34: 234-248, 1996[Medline]

14. Hürny C, Bernhard J, Bacchi M, et al: The Perceived Adjustment to Chronic Illness Scale (PACIS): A global indicator of coping for operable breast cancer patients in clinical trials. Support Care Cancer 1: 200-208, 1993[Medline]

15. Bernhard J, Hürny C, Coates AS, et al: Quality of life assessment in patients receiving adjuvant therapy for breast cancer: The IBCSG approach. The International Breast Cancer Study Group. Ann Oncol 8: 825-835, 1997[Abstract/Free Full Text]

16. Butow PN, Coates AS, Dunn S, et al: On the receiving end. IV: Validation of quality of life indicators. Ann Oncol 2: 597-603, 1991[Abstract/Free Full Text]

17. Coates AS, Glasziou PP, McNeil D: On the receiving end. III: Measurement of quality of life during cancer chemotherapy. Ann Oncol 1: 213-217, 1990[Abstract/Free Full Text]

18. Hürny C, Bernhard J, Gelber RD, et al: Quality of life measures for patients receiving adjuvant therapy for breast cancer: An international trial. International Breast Cancer Study Group. Eur J Cancer 28: 118-124, 1992

19. Bernhard J, Castiglione-Gertsch M, Schmitz SF, et al: Quality of life in postmenopausal patients with breast cancer after failure of tamoxifen: Formestane versus megestrol acetate as second-line hormonal treatment. Swiss Group for Clinical Cancer Research (SAKK). Eur J Cancer 35: 913-920, 1999

20. Bernhard J, Thürlimann B, Schmitz SF, et al: Defining clinical benefit in postmenopausal patients with breast cancer under second-line endocrine treatment: Does quality of life matter? J Clin Oncol 17: 1672-1679, 1999[Abstract/Free Full Text]

21. Cox DR: Regression models and life-tables (with discussion). J R Stat Soc B 34: 187-220, 1972

22. Bernhard J, Hürny C, Coates AS, et al: Factors affecting baseline quality of life in two international adjuvant breast cancer trials. International Breast Cancer Study Group (IBCSG). Br J Cancer 78: 686-693, 1998[Medline]

23. Coates AS, Gebski V: On the receiving end VI. Which dimensions of quality of life scores carry prognostic information? Cancer Treat Rev 22: 63-67, 1996

24. Dancey J, Zee B, Osoba D, et al: Quality of life scores: An independent prognostic variable in a general population of cancer patients receiving chemotherapy. The National Cancer Institute of Canada Clinical Trials Group. Qual Life Res 6: 151-158, 1997[Medline]

25. Kaasa S, Mastekaasa A, Lund E: Prognostic factors for patients with inoperable non-small cell lung cancer, limited disease. The importance of patients’ subjective experience of disease and psychosocial well-being. Radiother Oncol 15: 235-242, 1989[Medline]

26. Tamburini M, Brunelli C, Rosso S, et al: Prognostic value of quality of life scores in terminal cancer patients. J Pain Symptom Manage 11: 32-41, 1996[Medline]

27. Wilsoff F, Hjorth M: Health-related quality of life assessed before and during chemotherapy predicts for survival in multiple myeloma. Br J Haematol 97: 29-37, 1997[Medline]

28. Buccheri GF, Ferrigno D, Tamburini M, et al: The patient’s perception of his own quality of life might have an adjunctive prognostic significance in lung cancer. Lung Cancer 12: 45-58, 1995[Medline]

29. Spiegel D, Bloom JR, Kraemer HC, et al: The effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 2: 888-891, 1989[Medline]

30. Küchler T, Henne-Bruns D, Rappat S, et al: Impact of psychotherapeutic support on gastrointestinal cancer patients undergoing surgery: Survival results of a trial. Hepatogastroenterology 46: 322-335, 1999[Medline]

31. Fawzy FI, Fawzy NW, Hyun CS, et al: Malignant melanoma. Effects of an early structured psychiatric intervention, coping and affective state on recurrence and survival 6 years later. Arch Gen Psychiatry 50: 681-689, 1993[Medline]

32. Spiegel D, Sephton SE, Terr AI, et al: Effects of psychosocial treatment in prolonging cancer survival may be mediated by neuroimmune pathways. Ann N Y Acad Sci 840: 674-683, 1998[Medline]

33. Hürny C, Bernhard J: Coping and survival in patients with primary breast cancer: A critical analysis of current research strategies and proposal of a new approach integrating biomedical, psychological and social variables, in Senn H-J, Goldhirsch A, Gelber RD, et al (eds): Adjuvant Therapy of Primary Breast Cancer. Berlin, Germany, Springer, 1989, pp 255-271

34. Hürny C: Coping and survival in early breast cancer: An update, in Senn H-J, Gelber RD, Goldhirsch A, et al (eds): Adjuvant Therapy of Primary Breast Cancer IV. Berlin, Germany, Springer, 1993, pp 211-220

35. van der Pompe G, Antoni MH, Mulder CL, et al: Psychoneuroimmunology and the course of breast cancer: An overview. The impact of psychosocial factors on the progression of breast cancer through immune and endocrine mechanisms. Psychooncology 3: 271-288, 1994

36. Mulder CL, van der Pompe G, Spiegel D, et al: Do psychosocial factors influence the course of breast cancer? A review of recent literature, methodological problems and future directions. Psychooncology 1: 155-167, 1992

37. Tross S, Herndon J, Korzun A, et al: Psychological symptoms and disease-free and overall survival in women with stage II breast cancer. Cancer and Leukemia Group B. J Natl Cancer Inst 88: 661-667, 1996[Abstract/Free Full Text]

Submitted November 10, 1999; accepted June 21, 2000.

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				F. Cardoso, A. Di Leo, C. Lohrisch, C. Bernard, F. Ferreira, and M. J. Piccart Second and subsequent lines of chemotherapy for metastatic breast cancer: what did we learn in the last two decades? Ann. Onc., February 20, 2002; 13(2): 197 - 207. [Abstract] [Full Text] [PDF]

				A. Goldhirsch, J. H. Glick, R. D. Gelber, A. S. Coates, and H.-J. Senn Meeting Highlights: International Consensus Panel on the Treatment of Primary Breast Cancer J. Clin. Oncol., September 15, 2001; 19(18): 3817 - 3827. [Full Text] [PDF]

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