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Journal of Clinical Oncology, Vol 24, No 30 (October 20), 2006: pp. 4875-4881 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.2290 Quality of Life for Women Diagnosed With Breast Carcinoma in Situ
From the Departments of Epidemiology, and Public Health, and Pathology; Yale Comprehensive Cancer Center; Yale University School of Medicine, New Haven, CT; and the Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA Address reprint requests to Elizabeth B. Claus, MD, PhD, Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College St, PO Box 208034, New Haven, CT 06520-8034; e-mail: elizabeth.claus{at}yale.edu
PURPOSE: Limited data exist on long-term quality of life (QOL) for women diagnosed with breast carcinoma in situ (BCIS). PARTICIPANTS AND METHODS: The data are on 795 BCIS participants diagnosed among female residents of Connecticut from September 15, 1994 to March 14, 1998, and 702 controls frequency-matched to the case participants by 5-year age intervals and geography. These women were participants in a large, population-based case/control study and subsequent follow-up study. Telephone interviews at follow-up were used to collect data on QOL at 5 years from initial diagnosis or contact, using the Medical Outcomes Study, Center for Epidemiologic Studies-Depression, and CAGE (Cut down, Annoyed, Guilty, Eye-opener) alcohol consumption scales. QOL outcomes were compared by case/control status and by case treatment group: lumpectomy, lumpectomy with adjuvant radiation therapy, and mastectomy. RESULTS: At 5 years after diagnosis, women diagnosed with BCIS report levels of physical, emotional, and mental health functioning similar with those reported in a general healthy female population. Case participants and controls did not differ in reported levels of limitations due to physical health problems, bodily pain, social functioning, or overall physical functioning. Case participants who underwent lumpectomy with radiation reported lower levels of emotional functioning, general health perceptions, vitality, sexual interest, and overall mental health, as well as more depressive symptoms than did control subjects; although, the clinical significance of these statistical differences appears to be limited. CONCLUSION: At 5 years after treatment, women diagnosed with BCIS report good physical and emotional functioning relative to control populations.
Numerous studies examine psychosocial and medical outcomes for women diagnosed both recently as well as in the past with invasive breast carcinoma (IBC).1-10 However, data on quality of life (QOL) for women diagnosed with noninvasive breast carcinoma (ie, breast carcinoma in situ [BCIS]) appear to be limited to a single study of 83 patients,11 making further examination of this topic timely. The long-term QOL outcomes for women with BCIS might be expected to differ from those reported for women with IBC for several reasons. In particular, relative to women diagnosed with IBC, BCIS patients are offered similar options regarding surgical and radiation treatments but do not generally receive chemotherapy, a treatment frequently associated with substantial morbidity in breast cancer populations.2-4,7-9,11-14 Furthermore, the long-term prognosis for women diagnosed with BCIS is typically quite good with rates of ipsilateral recurrence and contralateral breast cancer each estimated at approximately 1% to 2% per year depending on treatment group12-16 and 5-year survival rates exceeding 95%.15 Hence, it is of interest to examine outcomes specifically for BCIS patients to better define whether similar intervention or counseling strategies are needed as for women with IBC. As mammographic screening efforts throughout the United States have intensified, so has the number of women diagnosed with BCIS, particularly ductal carcinoma in situ (DCIS), with up to 20% of screened breast cancer patients diagnosed with these lesions. A description of the clinical course and long-term QOL outcomes for this group of patients is especially important, in light of the fact that in the coming century up to one in 50 women in the United States will likely be diagnosed with this type of tumor during her lifetime.
The baseline case/control study population from which the women in this analysis are drawn includes all women diagnosed with BCIS among residents of Connecticut from September 15, 1994 to March 14, 1998.17 Participants were identified through the Rapid Case Ascertainment Shared Resource of the Yale Cancer Center (New Haven, CT) as well as the Connecticut Tumor Registry and were diagnosed between the ages of 20 and 79 years. Controls were female Connecticut residents selected by random-digit-dialing methods and frequency matched by 5-year age intervals to the case partipants. Study subjects with a previous history of breast cancer and/or a breast biopsy of unknown outcome were excluded. The study, designed to evaluate the association between family history as well as exogenous and endogenous hormonal factors with breast carcinoma in situ risk, was approved by the Yale University School of Medicine Human Investigation Committee as well as by the Connecticut Department of Public Health Human Investigation Committee. Case participants approved for contact by their physicians and controls were interviewed by telephone. Overall, 1,606 potential case participants and 1,445 potential controls were identified (Fig 1). Two hundred forty-one case participants and 74 controls were ineligible.17 Ninety-one percent of eligible case participants had a consenting physician. Among case participants with a consenting physician, 83% participated in the interview portion of the study. Among controls, the initial household screening response rate was 85.7%. These women were then contacted by our study; 81% agreed to be interviewed. The final sample included 1,068 case participants and 999 control subjects, with overall response rates of 76% and 70%, respectively. All case participants were identified by pathology report and confirmed via a uniform review. Further details of the study are presented elsewhere.17
In 2000, funding was secured to recontact participants of the initial case/control study. Study subjects who consented to the follow-up study were reinterviewed via telephone. Eight hundred four case participants (75%) have been reinterviewed. One hundred fifty-five case participants (14.5%) refused to participate, 64 case participants (6%) were deceased, 26 case participants (2.4%) were too ill to participate, and 19 case participants (1.8%) were not located. Among controls, 708 (71%) have been reinterviewed, 163 (16.3%) refused to participate, 56 (5.6%) were deceased, 21 (2.1%) were too ill to participate, and 51 (5%) were not located. Pathology reports for breast lesions reported since the time of the initial study have been collected. Nine case participants were found to have an IBC within 6 months of the initial diagnosis of in situ carcinoma and six controls were noted to have a past history of in situ or invasive breast cancer not previously reported to our study. These women were dropped from any further analyses, leaving 795 case participants and 702 controls. The follow-up interview included questions on QOL, depressive symptoms, and alcohol use. Health-related QOL was measured using the Medical Outcomes Study 36-item short form version (MOS SF-36).18 This instrument includes eight individual scales for physical functioning, role function-physical, bodily pain, social functioning, mental health, role function-emotional, vitality, and general health perceptions. Each scale is scored from 0 to 100, with 100 representing the best score. The SF-36 also has two summary scales: the Physical Component Summary scale and the Mental Component Summary scale. The summary scales are standardized to a reference healthy population with a mean score of 50 and a standard deviation of 10. The four-item Medical Outcomes sexual problems measure list,19 as well as several questions relating to employment and marital status, were also included. Depressive symptoms were measured using the Center for Epidemiologic Studies-Depression (CES-D) scale,20 a 20-item scale developed for the general population to measure self-reported depressive symptoms over the past week. Responses are scored on a 4-point scale with a maximum score of 60 representing the highest risk of depression. A score of 16 or greater is frequently used as an indicator of clinical depression. The CAGE (Cut down, Annoyed, Guilty, Eye-opener) screening questionnaire21 (scored from 0 to 4) was used to obtain information about the consumption of alcoholic beverages. In addition to data on QOL, case participants were asked whether they noted any adverse effects associated with their radiation treatment (if received), including pain, fatigue, and skin problems.
The analysis commenced with descriptive statistics and used t-tests,
A detailed presentation of the baseline characteristics of the initial case/control study population have been reported elsewhere17 but key details will be reported here for the sake of defining the population for whom our results are representative. The initial study correlated well to Connecticut Tumor Registry data with respect to race, age, histology, and socioeconomic status.17 The characteristics of participants from the initial and follow-up study (analyzed here) are similar with the exception that women who participated in the follow-up study were significantly younger than nonrespondents (54.9 v 64.9 years; P < .05). Study subjects from the follow-up sample were reinterviewed an average of 6.2 years after the date of the initial interview. Demographic characteristics of this sample by case/control status and by case participants treatment group are presented in Table 1. The mean age at onset/time of initial interview is 55.8 years for case participants, with the majority of case participants diagnosed with DCIS (87%) versus lobular carcinoma in situ (LCIS). The mean age for controls is 55.0 years. Controls are more likely than case participants to be premenopausal at reinterview (OR, 1.9; 95% CI, 1.4 to 2.6), with the difference explained by the fact that case participants treated with lumpectomy/radiation are more likely to be postmenopausal than are other study subjects. Case participants are less likely to be nonwhite (OR, 0.6; 95% CI, 0.4 to 0.9) than are controls. There are no significant differences by age, number of comorbid conditions, education, income, work status, or marital status by case/control status. Among case participants, 282 (36%) underwent lumpectomy, 397 (50%) underwent lumpectomy with adjuvant radiation therapy, and 111 (14%) underwent mastectomy. Five women reported no treatment. The majority of case participants diagnosed with LCIS (94%) were treated with lumpectomy alone while the majority of participants with DCIS (56.3%) underwent a lumpectomy followed by radiation therapy. There are no significant differences by age, race, number of comorbid conditions, education, income, work status, or marital status across case participant treatment group. Among women who received radiation therapy, 43.8% reported some adverse effect, with 19.1% reporting fatigue as the primary concern.
The majority (> 85%) of both case participants and controls reported having good/very good/excellent health at 5 years since last contact (Table 2) . The adjusted mean levels with standard deviations of the various MOS SF-36 health domains as well as CES-D scales are presented in Table 2. Case participants (overall and when examined by treatment group) and controls did not differ with respect to physical functioning, role limitations due to physical health problems, bodily pain, social functioning, or overall reported levels of physical functioning (MOS Physical Component Summary scale). With respect to alcohol consumption, no significant differences in CAGE score were reported between case participants and controls (0.23 v 0.28, respectively; P = .13). Statistically lower MOS SF-36 scores were reported for case participants versus controls for the following dimensions: general mental health, role limitations due to emotional problems, vitality, and general health perceptions, as well as for the overall mental health score (MOS Mental Component Summary scale). The mean adjusted CES-D score for case participants was significantly higher (indicating higher levels of depressive symptoms) than for controls. When examined further by case participants treatment group, these differences were generally due to the poorer scores of case subjects who underwent lumpectomy and radiation relative to control subjects. This group reported decreased levels of mental health and vitality, as well as higher levels of depressive symptoms, relative to controls. In one instance, the SF-36 score difference between case participants and controls (role limitations due to emotional problems) was due to lower scores for the lumpectomy only group versus the control group. No differences were appreciated by histologic subtype of breast lesion (DCIS v LCIS). Of note, despite the statistically significant differences in SF-36 and CES-D scores reported by group, the adjusted mean values for the four study groups were within a maximum of 0.25 standard deviations from one another for all MOS SF-36 domains as well as for the CES-D score.
Responses for sexual problems list are presented in Table 3. Case participants were significantly more likely than controls to report that a breast condition had ever interfered with sexual activity (13.3% v 3.1%, respectively); this finding was true regardless of case treatment category although low rates of marital status change associated with a breast condition were observed for all groups with no significant differences appreciated by case/control status. For each of the four MOS SF-36 sexual list questions, case participants were more likely than controls to report "somewhat of a problem" or "very much of a problem." When further examined by type of treatment received, case participants who had undergone lumpectomy (with or without radiation therapy) were more likely to report sexual problems than were controls or were participants who received a mastectomy.
We describe here the reported QOL for a large population-based series of women diagnosed with BCIS approximately 6 years from time of diagnosis/time of initial contact. To our knowledge, this is the first effort to examine these outcomes in such a sample both overall and by treatment group, as well as relative to an age-matched control group. The one previous study of QOL in women with DCIS included only 83 case participants—all of whom had undergone a lumpectomy with adjuvant radiation therapy11; an overall good QOL at a median of 4 years since treatment was noted. At 5 years from diagnosis, our results also suggest that case participants with BCIS report levels of physical, emotional, and mental health functioning similar to that of a general healthy female population.18 No statistical differences in physical functioning, role limitations due to physical health problems, bodily pain, social functioning, or overall reported levels of physical functioning were found either for all case participants combined or by case treatment group relative to controls, similar to reports of IBC survivors examined at 1 to 5 years after diagnosis.8,23 Statistical differences in emotional functioning by case/control group were appreciated with case participants more likely to report lower scores for vitality and mental health, as well as higher rates of depressive symptoms; although, it is unlikely that these small differences are clinically relevant.24,25 In most instances, these differences were attributable to the reduced scores of case participants who underwent lumpectomy and adjuvant radiation therapy relative to controls. Almost half of the case participants in this treatment group reported some radiation-related adverse effect, with fatigue representing the most commonly reported symptom. In the one previous study of QOL in DCIS patients,11 the authors concluded that radiation therapy did not affect QOL; however, the sample size was small. A number of researchers have previously reported that fatigue may persist for years after completion of breast cancer treatment; although, these data are primarily collected from women diagnosed with IBC who received adjuvant chemotherapy,1,4,27 a form of treatment generally not assigned to BCIS patients. With respect to surgical technique, a number of investigators have reported decreased physical or emotional functioning associated with mastectomy when compared with lumpectomy, although this appears to be more frequent in the short-term and the findings are not consistent.1-5,7-10,23,26 We did not observe such an association, due perhaps, in part, to the length of time since surgery and to the fact that surgical technique has greatly improved over time (particularly with respect to the methods used to perform axillary lymph node dissection). The rates of sexual problems reported here are similar to those of other studies,7,11 which include breast cancer patients of similar age and seem to indicate that in general, at 5 years from diagnosis, the majority of women report no major difficulties. Many of the problems reported appeared to be associated with increasing age and menopause. Of note, women undergoing lumpectomy reported more problems but were also more likely to be postmenopausal at time of interview than were women who underwent a mastectomy. Sexual and other problems associated with the use of tamoxifen reported in other studies6 were not seen here; however, fewer than one third of patients had ever used this medication in these data, likely due to the fact that results from clinical trials were not available to patients at the start of this study. Previous studies have noted more sexual problems reported by patients who received additional treatment than by patients who received surgery only, generally primarily associated with the use of chemotherapy.10 Our study benefits from a large, population-based sample of patients as well as a control group. The instruments used in this study (MOS SF-36, CES-D) have been previously validated and have population norms.18,20 The response rates for this study are consistent with those reported for other large case/control studies of cancer. Caveats for our analysis include the fact that women who agreed to participate were younger on average by several years than nonparticipants. Although age is included in the statistical modeling, it is possible that older women may have different levels of satisfaction with their lifestyles and outcomes than do younger women. In addition, despite representing a well-established QOL measure, the MOS SF-36 is somewhat generic in nature and will therefore not be specifically sensitive to breast cancer. Data on symptoms such as fatigue were collected for case participants and not controls, hence comparisons of these symptoms by case/control status are not possible. As QOL data was collected at only one point in time, the analyses are not able to control for baseline psychosocial status. Given the racial/ethnic background of our study population, our results are applicable primarily to a white population. Furthermore, although these data represent the largest collection of BCIS patients with QOL information, the numbers within some treatment groups are still relatively small. At 5 years from diagnosis and treatment, women diagnosed with BCIS report physical and emotional functioning that is generally in the normal range for healthy women.18 Case participants were more likely to have lower scores on a number of QOL dimensions that were primarily associated with emotional functioning, including role limitations due to emotional problems, vitality, and general mental health. In addition, case participants reported higher rates of depressive symptoms (although few case participants or controls reported being diagnosed with or treated for clinical depression). The differences noted between case participants and controls appeared to be attributable primarily to women who received adjuvant radiation therapy after lumpectomy rather than to women who underwent either a lumpectomy (without radiation) or a mastectomy and may suggest some decrease in emotional functioning associated with radiation therapy. The attribution of this statistical decrease in reported emotional functioning to the use of radiation therapy must be carefully considered as the assignment of BCIS patients to treatment is not random but based on a number of clinical and personal characteristics as well as patient and physician preference. Furthermore, it is unlikely that the statistical differences reported here are of clinical relevance given the fact that all of the between group differences were within 0.25 standard deviations of one another. Within the literature, the magnitude of differences reported here are generally regarded to be clinically insignificant (separated by less than one half of a standard deviation) for the QOL measures used in this project.24,25 Hence, these data indicate that, in general, the long-term prognosis for women diagnosed with BCIS is positive from physical, emotional, and as well as clinical, perspectives.
Participating Institutions: Bradley Memorial Hospital, Bridgeport Hospital, Bristol Hospital, Charlotte Hungerford Hospital, Danbury Hospital, Day-Kimball Hospital, Greenwich Hospital, Griffin Hospital, Hartford Hospital, Johnson Memorial Hospital, Lawrence and Memorial Hospital, Manchester Memorial Hospital, Middlesex Hospital, MidState Medical Center, Milford Hospital, New Britain General Hospital, New Milford Hospital, Norwalk Hospital, Rockville General Hospital, St Francis Hospital and Medical Center, St Mary's Hospital, Hospital of St Raphael, St Vincent's Medical Center, Sharon Hospital, Stamford Health System, University of Connecticut Health Center/John Dempsey Hospital, Waterbury Hospital, William W. Backus Hospital, Windham Hospital, and the Yale-New Haven Hospital.
The authors indicated no potential conflicts of interest.
We acknowledge the study participants as well as the hospitals of Connecticut (for a full listing of hospitals please see online only Appendix). Certain data used in this study were obtained from the Connecticut Tumor Registry located in the Connecticut Department of Public Health Study.
Supported by the US Army Medical Research and Material Command under Grant No. DAMD-17-95-1-5006 and by National Institutes of Health Grant No. R01-CA81393. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Andrykowski MA, Curran SL, Lighner R: Off-treatment fatigue in breast cancer survivors: A controlled comparison. J Behav Med 12:1-18, 1998[Medline] 2. Beisecker AE, Cook MR, Ashworth J: Side effects of adjuvant chemotherapy: Perceptions of node-negative breast cancer patients. Psychooncol 6:85-93, 1997[CrossRef][Medline] 3. Bergland G, Bolund C, Fornander T, et al: Late effects of chemotherapy and postoperative radiotherapy on quality of life among breast cancer patients. Eur J Cancer 27:1075-1081, 1991[Medline] 4. Brocckel 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] 5. Carpenter JS, Andrykowski MA, Sloan P, et al: Postmastectomy/postlumpectomy pain in breast cancer survivors. J Clin Epidemiol 51:1285-1292, 1998[CrossRef][Medline] 6. Day R, Ganz PA, Costantino JP, et al: Health-related quality of life and tamoxifen in breast cancer prevention: A report from the National Surgical Adjuvant Breast and Bowl Project P-1 Study. J Clin Oncol 17:2659-2669, 1999 7. Ganz PA, Desmond KA, Belin TR, et al: Predictors of sexual health in women after a breast cancer diagnosis. J Clin Oncol 18:2371-2380, 1999 8. Ganz PA, Rowland JH, Meyerowitz BE, et al: Impact of different adjuvant therapy strategies on quality of life in breast cancer survivors. Recent Results Cancer Res 152:396-411, 1998[Medline] 9. Ganz PA, Kwan L, Stanton AL, et al: Quality of life at the end of primary treatment of breast cancer: First results from the moving beyond cancer randomized trial. J Natl Cancer Inst 96:376-387, 2004 10. Mandelblatt J, Armetta C, Yabroff KR, et al: Descriptive review of the literature on breast cancer outcomes: 1990 through 2000. J Natl Cancer Inst 33:8-44, 2004 11. Amichetti M, Caffo O, Arcicasa M, et al: Quality of life in patients with ductal carcinoma in situ of the breast treated with conservative surgery and postoperative radiation. Breast Cancer Res Treat 54:109-115, 1999[CrossRef][Medline] 12. Cornfield DB, Palazzo JP, Schwartz GF, et al: The prognostic significance of multiple morphologic features and biologic markers in ductal carcinoma in situ of the breast. Cancer 100:2317-2327, 2004[CrossRef][Medline] 13. Fisher B, Constantino J, Redmond C, et al: Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 328:1581-1586, 1993 14. Fisher B, Land S, Mamounas E, et al: Prevention of invasive breast cancer in women with ductal carcinoma in-situ: An update of the National Surgical Adjuvant Breast and Bowel Project experience. Semin Oncol 28:400-418, 2001[CrossRef][Medline] 15. Claus EB, Stowe M, Carter D: The risk of a contralateral breast cancer among women diagnosed with ductal and lobular breast carcinoma in situ: Data from the Connecticut Tumor Registry. The Breast 12:451-456, 2003[Medline] 16. Kerlikowske K, Molinaro A, Cha I, et al: Characteristics associated with recurrence among women with ductal carcinoma in situ treated by lumpectomy. J Natl Cancer Inst 95:1692-1702, 2003 17. Claus EB, Stowe M, Carter D: Breast carcinoma in-situ: Risk factors and screening patterns. J Natl Cancer Inst 93:1811-1817, 2001 18. Ware JE Jr, Kosinski M, Gandek B: SF-36 Health Survey: Manual and Intepretation Guide. Lincoln, RI, Quality Metric Incorporated, 2005 19. Sherbourne CD: Social functioning: Sexual problems measures, in Stewart AL, Ware JE, (eds): Measuring Function and Well-Being: The Medical Outcomes Study Approach. Durham, NC, Duke University Press, 1992, pp 195-204 20. Randloff LS: The CES-D scale: A self-report depression scale for research in the general population. Appl Psychol Meas 1:385-401, 1977[CrossRef] 21. Ewing JA: Detecting alcoholism: The CAGE questionnaire. JAMA 252:1905-1907, 1984[Abstract] 22. SAS Institute Inc: SAS/STAT User's Guide, vol 1. Cary, NC, SAS Institute Inc, 1996 23. Dorval M, Maunsell E, Deschens L, et al: Long-term quality of life after breast cancer: Comparison of 8-year survivors with population controls. J Clin Oncol 16:487-494, 1998[Abstract] 24. Norman GR, Sloan JA, Wyrwich KW: Interpretation of changes in health-related quality of life: The remarkable universality of half a standard deviation. Med Care 41:582-592, 2003[CrossRef][Medline] 25. Wyrwich KW, Bullinger M, Aaronson N, et al: Estimating clinically significant differences in quality of life outcomes. Qual Life Res 14:285-295, 2005[CrossRef][Medline] 26. Curran D, van Dongen JP, Aaronson NK, et al: Quality of life of early stage breast cancer patients treated with radical mastectomy or breast-conserving procedures: Results of the EORTC trial 10801. Eur J Cancer 34:307-314, 1998[CrossRef][Medline] 27. Sanders ME, Schuyler PA, Dupont WD, et al: The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 103:2481-2484, 2005[CrossRef][Medline] Submitted December 29, 2005; accepted August 18, 2006.
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
2, and Fisher's exact tests as well as unadjusted odds ratios (OR) with 95% CIs to examine whether descriptive characteristics of the study population differed between case participants and control subjects. Analysis of variance tests were used to compare responses from the MOS sexual problems list and the CAGE scale by study group. Generalized linear models were used to provide adjusted estimates of MOS SF-36 and CES-D mean scores by study group. The effect of multiple comparisons was controlled for using a Bonferroni correction to make pairwise comparisons across the four study groups (three case participants treatment groups and the control group). Estimates of MOS SF-36 and CES-D means were adjusted for the effects of age, race (white/nonwhite), education (college degree/no college degree), menstrual status, comorbid conditions (myocardial infarction, stroke, cancer), time since treatment/interview, marital status (married/living as married v not) and case/control status. The MOS SF-36 variables were recoded according to the guidelines presented in Ware et al.
