Psychosocial Factors Associated with Delay in Diagnosis among Locally Advanced Breast Cancer Patients 

Donna Jeffe, Ph.D.,
Research Assistant Professor of Medicine 


Project Overview:
A. Background and Specific Aims 
Early diagnosis and treatment of breast cancer reduces mortality,[1] and delay in presentation of symptomatic disease is associated with poorer survival.[2] Development of strategies to encourage women to promptly seek evaluation of breast symptoms requires better understanding of factors that are associated with patient delays. Although a few informative literature reviews have been published on studies that looked at demographic factors associated with delay in patient presentation with breast disease,[3-5] little research has been published about women’s own reasons for delay in diagnosis. Therefore, we plan to submit a grant application (R01) to the National Cancer Institute on or before June 1, 2003 for a population-based study of reasons for delay in diagnosis among women with locally advanced breast cancer (LABC) using data from the Iowa Surveillance, Epidemiology and End Results (SEER) program. The proposed R01 also will assess differences in psychosocial and demographic variables between LABC (stages IIB, III, and IV) and non-LABC (stages I and IIA) patients, because we expect these two groups of patients to differ on many of the variables of interest. Results from the R01 should be helpful in developing interventions to encourage earlier detection. Collaborating with Dr. Donna Jeffe (PI) on the future R01 and proposed pilot study are Drs. Rebecca Aft, Mario Schootman, and Anat Reschke, all currently co-investigators on several funded studies. The members of this collaborative group have experience pertinent to the planned R01, including 1) using the rapid case ascertainment process of the Iowa SEER program, which reports cancer cases identified 3-6 months after diagnosis, 2) using a Computer-assisted Telephone Interview (CaTI) system to interview breast cancer patients, and 3) recruiting cancer patients diagnosed at all stages of disease. We are requesting funding from the Longer Life Foundation to conduct a necessary pilot study to strengthen our R01 application. The Specific Aims of the pilot study are to: 1) test for differences in response rates between LABC and non-LABC patients and between two recruitment strategies, 2) pilot the interview measures, and 3) test for recall bias by evaluating differences between the two recruitment strategies in the correct reporting of mode of detection (abnormal mammogram vs. palpable mass or other breast symptoms), type of surgery (if any), and receipt of radiation therapy. 

B. General Methodology
For this pilot study, we will recruit women presenting with a breast cancer diagnosis at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. Participants will complete one 30-45 minute telephone interview and will be paid $10 for their time. Four groups of 10 women each will be recruited. Two groups will include women with LABC, diagnosed at stages IIB, III, and IV, according to the criteria established by the American Joint Committee on Cancer (AJCC).[6] The other two groups will consist of women with non-LABC (stages I and IIA breast cancers). Women with prior in situ or invasive breast cancers, who are non-English speaking, or have cognitive impairments (e.g., from dementia) will be excluded. We also will compare two recruitment strategies, 4-6 weeks vs. 4-6 months after diagnosis. Thus, one group of LABC patients and one group of non-LABC patients will be recruited prospectively and interviewed within 4-6 weeks of being diagnosed. The other two groups of LABC and non-LABC patients will be identified from the medical records, having been diagnosed 4-6 months earlier (which is similar to rapid-reporting system of the SEER program), and randomly selected for inclusion. In the year 2000, there were 306 newly diagnosed patients at stages I and IIA and 79 patients at stages IIB, III, and IV treated at the Siteman Cancer Center. Therefore, we expect to have an ample pool of potential participants for the pilot study. One aim of this pilot study is to compare the two recruitment strategies with regard to recall bias. Significantly less accurate recall of how the tumor was detected, type of surgery, and receipt of radiation therapy (validated against the medical record) among the women recruited 4-6 months after diagnosis compared to those recruited 4-6 weeks after diagnosis would suggest that using the Iowa SEER rapid case ascertainment process might be problematic for the proposed R01. If there is a significant difference in recall between these two groups, we will propose to the NCI a study using a cohort of women with breast cancer recruited prospectively 4-6 weeks after diagnosis at the Siteman Cancer Center. If no difference, then we will propose using the Iowa SEER registry data. We would not be surprised to see differences in some of the psychosocial measures (e.g., depressed mood and state anxiety) between the two recruitment strategies, because measures of mood and state anxiety, for example, are not stable characteristics and might differ among patients recruited at different times after diagnosis. But we would not expect to observe differences in the measures of more stable traits (e.g., trait anxiety), a history of depression or abuse, or reasons for delay in diagnosis between women recruited 4-6 weeks and those recruited 4-6 months after diagnosis. Another aim of the study is to measure and compare the response rates of patients in the LABC and non-LABC groups and those patients recruited using the two recruitment strategies (as described in the Statistical Analysis section). The response rate was > 70% in our recent study of ductal carcinoma in situ and stage I breast cancer patients and > 60% in a study of late-stage lung cancer patients, but we need data about response rates among women with LABC in order to calculate power for the R01. The third aim is to pilot the interview measures to identify questions that are unclear to respondents and to see if we need to shorten the interview. Measures: During the interview, we will measure the following demographic, clinical, and psychosocial variables: date of birth, household income, highest level of education, race, Hispanic ethnicity, employment, health insurance, living alone or with others, smoking history, height and weight (to compute body mass index), AJCC stage and other tumor characteristics, cognitive impairment (only among women age 65 and older),[7] comorbidity,[8] quality of life using the Functional Assessment of Cancer Therapy-Breast (FACT-B) Version 4,[9] depressed mood using the Center for Epidemiologic Studies Depression (CES-D) survey,[10] history of depression using items based on DSM-IV criteria, severity of symptoms of anxiety using the Beck Anxiety Inventory (BAI),[11] trait anxiety using the State-Trait Anxiety Inventory (STAI),[12] social support using the Medical Outcomes Study (MOS) Social Support Survey,[13] women’s experiences of physical, sexual, and emotional abuse using an unpublished measure, women’s attitudes toward mammography,[14, 15] and for women with LABC, reasons for delay in diagnosis using a series of open-ended questions. Data Collection: Data will be collected 1) by telephone interview by Ms. Angela Boyd, who has extensive experience using the CaTI system and 2) from medical records. Ms. Michelle Jones will create the computer-based data collection screens. The electronic data will be compiled on a PC-based local area network and will be read directly into an SPSS data file, thus eliminating a source of data-entry error.

Data Management: 
Dr. Jeffe will be responsible for coordinating the overall planning and for data analysis. Ms. Jones will be responsible for all aspects of data management, including procedures for data transmittal to SPSS and data editing, as well as procedures for quality control and verification of data and procedures for data security and confidentiality.

Statistical Analysis: 
We will use SPSS 10.0 to perform the analyses. A p-value at or below 0.05 will be considered statistically significant. The distributions of all variables will be reviewed to assess the appropriateness of any outliers. Qualitative data (reasons for delay in diagnosis) will be analyzed using thematic analysis techniques.[16] Categories of reasons will be identified and the frequency of respondents giving reasons fitting into each category will be enumerated. The differences in correct reporting of mode of detection, type of surgery, and receipt of radiation therapy (to test recall bias) between the two recruitment strategies (4-6 weeks vs. 4-6 months after diagnosis) and the two diagnostic groups (i.e., non-LABC patients vs. LABC patients) will be assessed using chi-squared tests. Response rates will be calculated by dividing the number of participants by the number of recruitment letters sent out. Between-groups differences in the psychosocial measures will be tested using analysis of variance (or Mann-Whitney U-tests if data are highly skewed).

References 
1. Nyström L, Andersson I, Bjurstam N, Frisell J, Nordenskjöld B, Rutqvist LE. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 2002; 359:909-919. 
2. Richards MA, Westcombe AM, Love SB, Littlejohns P, Ramirez AJ. Influence of delay on survival in patients with breast cancer: a systematic review. Lancet 1999; 353:1119-1126. 
3. Caplan LS, Helzlsouer KJ. Delay in breast cancer: a review of the literature. Public Health Rev 1992/1993; 20:187-214. 
4. Facione NC. Delay versus help seeking for breast cancer symptoms: a critical review of the literature on patient and provider delay. Soc Sci Med 1993; 36:1521-1534.
5. Ramirez AJ, Westcombe AM, Burgess CC, Sutton S, Littlejohns P, Richards MA. Factors predicting delayed presentation of symptomatic breast cancer: a systematic review. Lancet 1999; 353:1127-1131.
6. American Joint Committee on Cancer, Manual for staging of cancer, 5th ed. 1997, Philadelphia, PA: Lippincott-Raven Publishers. 
7. Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H. Validation of a short Orientation-Memory-Concentration test of cognitive impairment. Am J Psychiatry 1983; 140:734-739. 
8. Katz JN, Chang LC, Sangha O, Fossel AH, Bates DW. Can comorbidity be measured by questionnaire rather than medical record review? Med Care 1996; 34(1):73-84.
9. Brady MJ, Cella DF, Mo F, Bonomi AE, Tulsky DS, Lloyd SR, Deasy S, Cobleigh M, Shiomoto G. Reliability and validity of the functional assessment of cancer therapy-breast quality of life instrument. J Clin Oncol 1997; 15:974-986. 
10. Radloff LS. The CES-D scale: A self-report depression scale for research in the general population. Appl Psychological Measurement 1977; 1:385-401. 
11. Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: Psychometric properties. J Consult Clin Psychol 1988; 56:893-897.
12. Spielberger CD, Manual for the State-Trait Anxiety Inventory STAI (Form Y). 1983, Palo Alto, CA: Mind Garden. 
13. Sherbourne C, Stewart A. The MOS social support survey. Soc Sci Med 1991; 32:705-714. 
14. Champion VL. Instrument refinement for breast cancer screening behaviors. Nurs Res 1993; 42:139-143. 
15. Skinner CS, Arfken CL, Sykes RK. Knowledge, perceptions, and mammography stage of adoption among older urban women. Am J Prev Med 1998; 14:54-63. 
16. Miles M, Huberman A, Qualitative data analysis. 1984, Beverly Hills, CA: Sage.


Final Report:
Early diagnosis and treatment of breast cancer reduces mortality, and delay in presentation of symptomatic disease is associated with poorer survival. Development of strategies to encourage women to promptly seek evaluation of breast symptoms requires better understanding of factors that are associated with patient delays. Although informative literature reviews have been published on studies that looked at demographic factors associated with delay in patient presentation with breast disease, little research has been published about women’s own reasons for delay in diagnosis. To address this issue, we plan to submit a grant application to the National Cancer Institute for a population-based study of reasons for delay in diagnosis among women with locally advanced breast cancer using data from the Iowa Surveillance, Epidemiology and End Results (SEER) program. The proposed R01 also will assess differences in psychosocial and demographic variables between LABC (stages IIB, III, and IV) and non-LABC (stages I and IIA) patients, because we expect these two groups of patients to differ on many of the variables of interest. Results from the R01 should be helpful in developing interventions to encourage earlier detection among women at higher risk for presenting with late-stage breast cancer. Read the full Final Report.