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Quality of Life in Women With Breast Cancer During the First Year After Random Assignment to Adjuvant Treatment With Marrow-Supported High-Dose Chemotherapy With Cyclophosphamide, Thiotepa, and Carboplatin or Tailored Therapy With Fluorouracil, Epirubicin, and Cyclophosphamide: Scandinavian Breast Group Study 9401

Yvonne Brandberg, Helena Michelson, Bo Nilsson, Christina Bolund, Bjørn Erikstein, Päivi Hietanen, Stein Kaasa, Jonas Nilsson, Tom Wiklund, Nils Wilking, Jonas Bergh

From the Department of Oncology-Pathology, Karolinska Institutet, Stockholm; Regional Oncologic Center, Uppsala, Sweden; Norwegian Radium Hospital, Oslo; Regional Hospital, Trondheim, Norway; and University Hospital, Helsinki, Finland.

Address reprint requests to Jonas Bergh, MD, PhD, Department of Oncology, Karolinska Hospital, S-171 76 Stockholm, Sweden; e-mail: Jonas.Bergh{at}cck.ki.se.

	ABSTRACT

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Purpose: To compare, in high-risk breast cancer patients, the effects on health-related quality of life (HRQoL) of two adjuvant treatments. Treatments were compared at eight points during the first year after random assignment to treatment with tailored fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy for nine courses versus induction FEC therapy for three courses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb) supported by peripheral-blood stem cells.

Patients and Methods: From March 1994 to March 1998, 525 breast cancer patients (estimated relapse risk > 70% within 5 years with standard therapy) were included in the Scandinavian Breast Group 9401 study. HRQoL evaluation, using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Breast Cancer Module–23, included 408 of 446 eligible patients in Finland, Norway, and Sweden.

Results: Eighty-four percent to 95% of the patients completed questionnaires at eight points of assessment. Nostatistically significant overall differences were found between the tailored FEC group and the CTCb group for any of the HRQoL variables. Statistically significant differences over time were found for all HRQoL variables. HRQoL in the CTCb group demonstrated a steeper decrease, but a faster recovery than in the tailored FEC group. Emotional functioning improved with increased time from randomization. Higher levels of problems in body image and arm symptoms were reported in the tailored FEC group compared with the CTCb group. Sexual functioning and satisfaction were impaired during the study period.

Conclusion: Both treatments had a negative influence on HRQoL during the treatment period. Despite the aggressive therapies, the patient’s HRQoL returned to levels found at inclusion on most variables.

	INTRODUCTION

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ADJUVANT THERAPY for breast cancer is the medical oncologic therapy modality that likely is saving the most lives.¹ Despite this, many patients experience relapse and will ultimately die from metastatic breast cancer. Dose escalation above conventional doses has so far not resulted in survival improvements, but lower than standard doses result in an inferior outcome.² A recent study, however, demonstrated a benefit from administration of epirubicin in higher doses.³ The use of even higher chemotherapy doses (ie, high-dose therapy with autologous bone marrow support) or the additional support (in recent years) of peripheral-blood stem cells (PBSCs) in uncontrolled studies indicated a survival gain, both in the adjuvant and in the metastatic setting.⁴ Randomized phase III studies have so far been unable to support the phase II data.^5–9 A recent study, however, indicates a potential benefit by the marrow-supported high-dose therapy.¹⁰

From March 1994 to March 1998, 525 high-risk breast cancer patients were randomly assigned to two different adjuvant regimens. Nine courses of tailored and granulocyte colony-stimulating factor (G-CSF)–supported fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy (the tailored FEC group) was compared with induction FEC therapy for three courses followed by high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTCb) supported by PBSCs (the CTCb group).⁹ Both randomization arms were expected to have substantial side effects, thus evaluation of quality of life (QoL) was included as a secondary end point.

After a median follow-up of 34 months, statistically significantly fewer breast cancer relapses (P = .04) were recorded in the tailored and dose-escalated FEC arm (the tailored FEC group) compared with the FEC plus CTCb arm (the CTCb group); 81 v 113 relapses respectively. The overall survival was not statistically different (P = .12); 60 deaths occurred in the tailored FEC group versus 81 deaths in the CTCb group.⁹

The aim of this article is to compare the effects of the two treatment regimens on health-related QoL (HRQoL) during the first year after random assignment to treatment. HRQoL in this study consisted of six dimensions from the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30; which includes measures of physical functioning [PF], role functioning [RF], emotional functioning [EF], social functioning [SF], global QoL, and fatigue [FA]) and five dimensions from the EORTC QLQ–Breast Cancer Module (BR)–23 (which includes measures of body image, sexual functioning, systemic therapy side effects, breast symptoms, and arm symptoms). In addition, the objective toxicity measurements at the third course were correlated to the HRQoL scores.

	PATIENTS AND METHODS

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Patients
High-risk breast cancer patients who were younger than 60 years, had histologically confirmed breast cancer, an estimated 5-year relapse-free survival of 30% or less, and a life expectancy exceeding 3 months, were included in the Scandinavian Breast Group (SBG) 9401 study. Inclusion and exclusion criteria have been outlined elsewhere.⁹

In Finland and Sweden, the HRQoL evaluation started in October 1994; in Norway, the HRQoL evaluation started June 1995 (after the start of the clinical trial in all three locations). Denmark did not participate in the HRQoL study. Those participating patients received oral and written information about the HRQoL study. Written informed consent was obtained in that the patients approving to participate sent their names, addresses, and phone numbers to the study coordinator. The HRQoL amendment was approved by the ethical committees with jurisdiction for the study in all three participating countries.

Treatment Regimens
In the tailored FEC group, the aim was to tailor the FEC doses individually to a similar level of hematologic toxicity to avoid underdosage and overdosage of chemotherapy. Six doses were used in the tailored FEC group. The courses were given with 3-week intervals for nine courses. From March 1998, the regimens in the tailored FEC group were changed to six courses, without further dose escalations. The dosing has been described in detail elsewhere.^1,8 In the CTCb group, patients received three courses of FEC before high-dose chemotherapy. PBSCs were collected about 10 days after the third FEC. The high-dose therapy was planned to be given 3 to 4 weeks after the last FEC, but when PBSCs could not be delivered within 3 to 4 weeks after collection, a fourth course of FEC was recommended. The FEC therapy in the tailored FEC group was given with G-CSF support from days 2 to 15 and prophylactic antibiotics from days 5 to 15. In the CTCb arm, G-CSF was given in conjunction with the third course for collection of PBSCs and after reinfusion of the bone marrow product. At baseline and after each chemotherapy course toxicity was evaluated for the following National Institute common toxicity criteria toxicity items: anorexia, diarrhea, nausea, vomiting, stomatitis, infections, hematuria, bone pain, and myalgia.⁸ Alopecia was also assessed.

Locoregional radiotherapy was given daily in 2-Gy fractions five times per week to a total dose of at least 46 Gy, starting as soon as possible after the last course of chemotherapy. All patients, irrespective of receptor status, were to be given tamoxifen for 5 years nonconcurrently with chemotherapy.

Points of Assessment
HRQoL was assessed at eight points during the first year from random assignment to treatment (Table 1). The assessment points were intended to capture the times after random assignment to treatment when the patients were expected to experience the greatest number of problems and the highest intensity of problems.

Instruments
The EORTC QLQ-C30 was developed by the EORTC QoL Study Group for the measurement of QoL in cancer patients in clinical trials.¹¹ The EORTC QLQ-C30+3 is the third generation of the core questionnaire and was the version available at the start of this study. It consists of 33 items, incorporating five single-item scales and nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (FA, pain, and nausea or vomiting); and three global health and QoL items. The validity and reliability of the Swedish version of the EORTC QLQ C-36 were established in studies of patients with lung cancer¹² and in patients with metastatic cutaneous malignant melanoma.¹³ Normative data are published for the Norwegian¹⁴ and for the Swedish populations.¹⁵ Mean scales and item scores were transformed to a 0 to 100 scale according to the EORTC scoring manual.¹⁶

EORTC BR-23
The EORTC BR-23 is a breast cancer–specific questionnaire and is meant for use complementary to the generic EORTC QLQ-C30 for patients with different disease stages and treatment modalities.¹⁷ It comprises 23 items divided in four functioning scales (body image, sexual functioning, sexual satisfaction, and future perspective) and four symptom scales (side effects of systemic therapy, breast symptoms, arm symptoms, and upset by hair loss). The questionnaire has been validated in an international study.¹⁷

Statistical Methods
Mean values and standard deviations (SDs) are given for the randomization groups, respectively, at each point of assessment. Missing values were not substituted. Analyses of variance with repeated measurements were used to evaluate the impact of time and between group differences simultaneously. Differences at the third and fourth point of assessment between patients receiving marrow-supported, high-dose chemotherapy with CTCb before and after the third assessment point were analyzed by Student’s t test. Analyses of differences in proportions of patients in each randomization arm who were or were not having problems were performed by ² test.

Spearman rank correlations were calculated for the association between the HRQoL variables and the 10 toxicity items measured at the third course. This point was chosen because toxicity was supposed to be substantial after three courses of tailored FEC and because both groups had received the same treatment to that point, although at markedly different dose levels. Questionnaires completed within 2 weeks from the toxicity ratings were used.

	RESULTS

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Of 525 women randomly assigned in the SBG 9401 from March 1994 to March 1998, 446 were included in the HRQoL study (November 1994 to March 1998). Denmark (n = 10) did not take part in the HRQoL study. Of the 446 eligible patients, 408 patients (91%) participated in the HRQoL-study; 110 patients (26%) in Finland, 90 patients (21%) in Norway, and 208 patients (53%) in Sweden. A total of 197 patients (48%) were randomly assigned to the tailored FEC group and 211 patients (52%) were randomly assigned to the CTCb group. The mean age was 47.8 years (range, 25 to 61 years) in both arms. Fourteen patients in Finland, three patients in Norway, and 21 patients in Sweden were not included in the HRQoL part of the SBG 9401; it is not known why these women were not included.

A total of 54 patients were withdrawn from the HRQoL study during the first year. Twenty patients (5%) died within 1 year from random assignment; five in the tailored FEC group and 15 in the CTCb group. A total of 34 patients were lost to follow-up in the HRQoL study because of administrative failure during the first year; 15 in the tailored FEC group and 19 in the CTCb group. The response frequency at the various assessment points varied between 95% and 84% of the total number of patients included in the HRQoL evaluation. There were no statistically significant differences (²) between the treatment arms in proportion of patients returning questionnaires at any of the assessment points.

For all tested variables the proportion of missing values in returned questionnaires ranged from 0% to 7%. The largest proportion of missing values was found for SF after 16 weeks (6%) and for PF after 25 weeks (7%). Between 97% and 100% of patients completed the EF and the FA scales.

There were no differences, with respect to HRQoL variables, at the assessment before random assignment between patients who fulfilled the first year of assessment and those who where lost to follow-up.

HRQoL Variables
The mean values and SDs for the EORTC QLQ-C30 variables at eight assessment points are listed in Table 2.

Because of the finding that patients in the CTCb group scored higher regarding SF than those in the tailored FEC group at random assignment, analyses of differences in changes from baseline over time were performed. These analyses showed no difference between the tailored FEC group and the CTCb group after week 10.

Breast Cancer–Specific and Treatment-Specific Problems
Mean values and SDs for the two treatment arms on five breast cancer–specific scales before random assignment and after 16, 30, and 42 weeks are listed in Table 3. Patients in the CTCb group reported statistically significantly better body image than those in the tailored FEC group (F_288,1 = 14.1; P < .001). However, patients in the CTCb group reported higher levels of arm symptoms than patients in the FEC group (F_288,1 = 7.5; P < .01).

	DISCUSSION

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A total of 5,942 patients with different high-risk features have been included in studies comparing different marrow-supported high-dose therapy regimens versus different non–marrow-supported regimens.¹⁸ So far, no study has reported a survival benefit for the marrow-supported high-dose procedure when compared with various types of control arms not including marrow support. Acute toxicity is associated with the delivery of chemotherapy, especially in marrow-supported high-dose therapy. Thus, HRQoL was observed during the first year after random assignment to treatment.

As expected, HRQoL in both arms decreased during the first weeks of treatment but returned to levels similar to those found at random assignment for most HRQoL dimensions, which is consistent with the findings in other studies of HRQoL among patients undergoing marrow-supported high-dose chemotherapy with CTCb^19–23 and among patients receiving dose-escalated chemotherapy.²⁴ Clinical impressions suggest that patients undergoing high-dose therapy with marrow support suffer considerably.²⁵ As expected, patients who had recently undergone CTCb scored lower on the functional variables and higher on FA symptoms, which is consistent with other research of the HRQoL effects of high-dose therapy with marrow support.^19,22

Patients in the tailored FEC arm had a longer period of decreased HRQoL than patients in the CTCb group. However, patients in the tailored FEC group received treatment for a longer period. The assessment points are therefore not comparable with respect to time from treatment. The differences in time from random assignment were analyzed considering the fact that these two adjuvant treatments were likely to influence the patients’ HRQoL during a relatively long period of time.

EF increased during the first year from random assignment in both groups. This is in concordance with a French study in which EF increased during the first year after random assignment.²² In a longitudinal study of the adaptation to high-dose therapy with marrow support, hospitalization before CTCb was found to be the most emotionally distressing period, whereas the least distressing times were 3 months and 1 year after random assignment.¹⁹ EF among women in the general Swedish population, measured by the same instrument,¹⁵ was 78.3, compared with 76.9 in the tailored FEC group and 79.7 in the CTCb group 1 year after random assignment. If one takes into account that these women were in the process of coping with high-risk cancer and about to go back to normal life, their EF scores are better than may be expected.

Compliance in the HRQoL study was high compared with compliance in other studies.²² The questionnaires were sent by mail to the patients’ homes at certain time points after randomization. The drawback with this procedure is that the results mainly refer to the patients’ QoL at certain time points during the first year after random assignment, not to points during the time of treatment. However, the time for CTCb was of special interest. Data from the third assessment were therefore analyzed with respect to differences between patients who had CTCb before and after week 10. The results indicate a substantial influence on HRQoL at that time for CTCb.

The patients in both arms suffered substantially from FA symptoms during the course of treatment, but FA diminished after termination of treatment. Long-term studies of breast cancer patients have shown high levels of FA,^26,27 although two thirds of breast cancer survivors in a large study from the United States reported levels comparable to those of the general population.²⁸

As expected, sexual functioning and body image were impaired during the most burdensome treatment period, but persisted also at the 42-week assessment, consistent with other studies of patients undergoing chemotherapy for breast cancer.²⁹

Although women in both groups had undergone surgery for breast cancer before the inclusion in the study, after 30 and 42 weeks, women in the FEC arm reported lower mean scores concerning arm symptoms than those in the CTCb arm. This result might be because of a higher degree of physical inactivity for some weeks during the CTCb regimen. Arm problems have been reported as one of the most frequent and long-lasting consequences of breast cancer treatment.³⁰

The low correlations between toxicity ratings and patients’ HRQoL results found in the present study indicate that toxicity ratings cannot be used as indicators of HRQoL, and also support the assessment of patients’ HRQoL as a supplementary end point in cancer clinical trials.³¹

The results of this and other studies of breast cancer patients’ QoL during adjuvant chemotherapy^22,24,32 indicate that although adjuvant chemotherapy has negative effects on QoL during treatment, these effects tend to decline after the end of treatment. It has been suggested, as an explanation of the return to normal levels, that this group of women, who have high-risk breast cancer and have received burdensome treatment, change their points of reference with respect to QoL.^22,33 In a study on treatment preferences among 40 breast cancer patients presented with frames of outcome probabilities, decisions against adjuvant chemotherapy occurred only when the probabilities were low and the benefit of the treatment was considered small.³⁴

In conclusion, patients in the standard FEC followed by marrow-supported CTCb therapy had more pronounced deterioration of their HRQoL, but returned more quickly to original levels compared with patients receiving the more protracted therapy with the dose-escalated and tailored FEC regimen. Thus, although both treatments had substantial negative impact on most HRQoL areas, EF increased and most patients seemed to recover after this burdensome adjuvant treatment.

	APPENDIX

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The following institutions and participants were included in the SBG 9401-study. Sweden: Jonas Bergh, Nils Wilking, Radiumhemmet, Astrid Gruber, Karolinska Hospital; Per Ljungman, Huddinge Hospital; Dagny Petterson-Sköld, Danderyds Hospital; Tommy Fornander, Södersjukhuset, Stockholm; Henrik Lindman, Martin Höglund, Mats Bengtsson, University Hospital, Uppsala; Nils-Olov Bengtsson, Eva Löfvenberg, University Hospital, Umeå; Kenneth Villman, Örebro Hospital, Örebro; Gustaf Söderlund, Karin Karlsson, University Hospital, Linköping; Ragnar Hultborn, Susanne Ottosson, Jan Mattson, Svante Jansson, University Hospital; Göran Carlsson, Stig Röjder, Östra Hospital, Göteborg; Per Malmström, Margareta Palm-Sjövall, Bengt Sallerfors, University Hospital, Lund; Johan Ahlgren, Ann Gawelin, Gävle Hospital, Gävle; Martin Söderberg, Karlstad Hospital, Karlstad; Jörgen Hansen, Västerås Hospital, Västerås; Britta Stenstam, Mälarsjukhuset, Eskilstuna; Jan-Henry Svensson, Borås Hospital, Borås; Bengt Norberg, Ryhov Hospital, Jönköping. Norway: Bjørn Erikstein, Harald Holte, Gunnar Kvalheim, Norwegian Radiumhospital; Hilde Heen Sommer, Jon Magnus Tangen, Ullevål Hospital, Oslo; Gun Anker, Haukeland Hospital, Bergen; Steinar Lundgren, Regional Hospital, Trondheim; Erik Wist, Regional Hospital, Tromsø. Finland: Tom Wiklund, Carl Blomqvist, University Hospital, Helsinki; Eeva Salminen, Kari Remes, University Hospital, Turku; Marja Lehtinen, Elli Koivinen, Pirkko Kellokumpu-Lehtinen, University Hospital, Tampere; Taina Turpeenneiemi-Hujanen, Outi Kuittinen, Oulu University Hospital; Leena Voutilainen, Kuopio University Hospital. Denmark: Carsten Rose, Manssor Raza Mirza, University Hospital, Odense.

	AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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The authors indicated no potential conflicts of interest.

	ACKNOWLEDGMENTS

 
We are grateful to the patients who participated in this study.

	NOTES

 
Supported by grants from the Nordic Cancer Union and the Swedish Cancer Society, and by Amgen/Roche (filgrastim) and Pharmacia Upjohn.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION APPENDIX AUTHORS’ DISCLOSURES OF... REFERENCES

 
1. Bergh J: Where next with stem-cell supported high-dose therapy for breast cancer? Lancet 355:944–945, 2000[CrossRef][Medline]

2. Hortobagyi GN: Progress in systemic chemotherapy of primary breast cancer: An overview. J Natl Cancer Inst Monogr 30:72–79, 2001

3. The French Adjuvant Study Group: Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node-positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J Clin Oncol 19:602–611, 2001[Abstract/Free Full Text]

4. Peters W, Ross M, Vredenburgh J, et al: High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer. J Clin Oncol 11:1132–1143, 1993[Abstract/Free Full Text]

5. Rodenhuis S, Richel D, van der Wall E, et al: Randomized trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 352:515–521, 1998[CrossRef][Medline]

6. Hortobagyi GN, Buzdar AU, Theiault RL, et al: Randomized trial of high-dose chemotherapy and blood cells autografts for high-risk primary breast carcinoma. J Natl Cancer Inst 92:225–233, 2000[Abstract/Free Full Text]

7. Peters WP, Rosner G, Vredenburhg J, et al: Updated results of a prospective, randomized comparison of two doses of combination alkylating agents (AA) as consolidation after CAF in high-risk primary breast cancer involving ten or more axillary lymph nodes (LN): CALGB 9082/SWOG 9114/NCIC Ma-13. Proc Am Soc Clin Oncol 20:21a, 2001 (abstr 81)

8. Bergh J, Wiklund T, Erikstein B, et al: Tailored FEC compared with marrow-supported high-dose chemotherapy as adjuvant treatment of high-risk breast cancer patients: Results from a randomised study. Lancet 356:1384–1391, 2000[CrossRef][Medline]

9. Gianni A, Bonadonna G: Five-year results of the randomized clinical trial comparing standard versus high-dose myeloablative chemotherapy in the adjuvant treatment of breast cancer with more than 3 positive nodes (LN+). Proc Am Soc Clin Oncol 20:21a, 2001 (abstr 80)

10. Rodenhuis S, Bontebal M, Beex L, et al: Randomized phase III study of high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin in operable breast cancer with 4 or more axillary nodes. Proc Am Soc Clin Oncol 19:74a, 2000 (abstr 286)

11. Aaronson NK, Ahmedzai S, Bergman B, et al: The European organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376, 1993[Abstract/Free Full Text]

12. Bergman B, Sullivan M, Sörenson S: Quality of life during chemotherapy for small cell lung cancer: I. An evaluation with generic health measures. Acta Oncol 30:947–957, 1991[Medline]

13. Sigurdardottir V, Brandberg Y, Sullivan M: Criterion-based validation of the EORTC QLQ C-36 in advanced melanoma: The CIPS questionnaire and proxy raters. Qual Life Res 5:375–386, 1996[CrossRef][Medline]

14. Hjermstad MJ, Fayers PM, Bjordal K, et al: Health-related quality of life in a general Norwegian population assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire: The QLQ-C30 (+3). J Clin Oncol 16:1188–1196, 1998[Abstract]

15. Michelson H, Bolund C, Nilsson B, et al: Health-related quality of life measured by the EORTC QLQ-C30: Reference values from a large sample of Swedish population. Acta Oncol 39:477–484, 2000[CrossRef][Medline]

16. Fayers PM, Aaronson NK, Bjordal K, et al: EORTC QLQ-C30: Scoring Manual. Brussels, Belgium, European Organization for Research and Treatment of Cancer Quality of Life Study Group, 1995

17. Sprangers MAG, Groenvold M, Arraras JI, et al: The EORTC breast cancer-specific quality-of-life questionnaire module: First results from a three-country field study. J Clin Oncol 14:2756–2768, 1996[Abstract/Free Full Text]

18. Nieto Y: The verdict is not in yet: Analysis of the randomized trials of high-dose chemotherapy for breast cancer. Hematologica 88:201–211, 2003[Abstract/Free Full Text]

19. Fife BL, Huster GA, Cornetta KG, et al: Longitudinal study of adaptation to the stress of bone marrow transplantation. J Clin Oncol 18:1539–1549, 2000[Abstract/Free Full Text]

20. Hjermstad MJ, Kaasa S: Quality of life in adult cancer patients treated with bone marrow transplantation: A review of the literature. Eur J Cancer 31A:163–173, 1995[Medline]

21. Hjermstad MJ, Evensen SA, Kvaløj SO, et al: Health-related quality of life 1 year after allogenic or autologous stem-cell transplantation: A prospective study. J Clin Oncol 17:706–718, 1999[Abstract/Free Full Text]

22. Macquart-Moulin G, Viens P, Palangié T, et al: High-dose sequential chemotherapy with recombinant granulocyte colony-stimulating factor and repeated stem cell support for inflammatory breast cancer patients: Does impact on quality of life jeopardize feasibility and acceptability of treatment? J Clin Oncol 18:754–764, 2000[Abstract/Free Full Text]

23. Syrala KL, Chapko MK, Vitalino PP, et al: Recovery after allogenic marrow transplantation: Prospective study of predictors of long-term physical and psychosocial functioning. Bone Marrow Transplant 11:319–327, 1993[Medline]

24. Swain SM, Rowland J, Weinfurt K, et al: Intensive outpatient adjuvant therapy for breast cancer: Result of dose escalation and quality of life. J Clin Oncol 14:1565–1572, 1996[Abstract/Free Full Text]

25. Foelber R: Autologous stem cell transplant plus interleukin-2 for breast cancer: Review and nursing management. Oncol Nurs Forum 25:563–568, 1998[Medline]

26. Andrykowski MA, Curran SL, Lighner R: Off-treatment fatigue in breast cancer survivors: A controlled comparison. J Behav Med 21:1–18, 1998[CrossRef][Medline]

27. Broeckel JA, Jacobsen PB, Horton J, et al: Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer. J Clin Oncol 16:1689–1696, 1998[Abstract]

28. Bower J, Ganz P, Desmond KA, et al: Fatigue in breast cancer survivors: Occurrence, correlates, and impact on quality of life. J Clin Oncol 18:743–753, 2000[Abstract/Free Full Text]

29. Schover LR, Yetman RJ, Tuason LJ, et al: Partial mastectomy and breast reconstruction: A comparison of their effects on psychosocial adjustment, body image and sexuality. Cancer 75:54–64, 1995[CrossRef][Medline]

30. Maunsell E, Brisson J, Deschenes L: Arm problems and psychological distress after surgery for breast cancer. Can J Surg 36:315–379, 1993[Medline]

31. Louma ML, Hakamies-Blomqvist L, Sjöström J, et al: Physical performance, toxicity, and quality of life as assessed by the physician and the patient. Acta Oncol 41:44–49, 2002[CrossRef][Medline]

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

33. Sprangers MAG, van Dam FSAM, Broersen J, et al: Revealing response shift in longitudinal research on fatigue. Acta Oncol 38:709–718, 1999[CrossRef][Medline]

34. Zimmermann C, Baldo C, Molino A: Framing of outcome and probability of recurrence: Breast cancer patients’ choice of adjuvant chemotherapy (ACT) in hypothetical patient scenarios. Breast Cancer Res Treat 60:9–14, 2000[CrossRef][Medline]

Submitted July 6, 2003; accepted July 23, 2003.

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