Validity of information obtained from a method for estimating cancer costs from the perspective of patients and caregivers.

PURPOSE: We describe a method we developed for estimating cancer costs from the perspective of patients and caregivers and evidence supporting validity of estimates obtained. METHODS: To increase validity, interview questions were anchored to treatments; costs were divided into their components; most questions focused on facts; and the research team combined responses into cost estimates. Evidence for validity comes from a prospective study of breast cancer costs using this method. RESULTS: Estimates obtained using interview responses were similar to those from independent sources. Women reported being reimbursed $205 on average for prosthesis (government reimbursement =$200); paying $15.48 per night at cancer lodge (average rate =$17.52); receiving government illness insurance for 14.6 weeks at 53% of usual salary (governmental program covers 15 weeks at 55%). A priori hypotheses about relations of costs with other characteristics were also confirmed. For example, patients' weekly travel costs increased as a function of distance from the radiotherapy center, with patients living <25, 25-49 and ≥50 km away spending $54, $141 and $240, respectively (P<.0001); and the proportion of annual salary lost was 37% for self-employed workers compared to 18% for employees (P<.0001). CONCLUSIONS: Evidence to date supports the validity of estimates obtained using this method.

Wage losses in the year after breast cancer: extent and determinants among Canadian women.

BACKGROUND: Wage losses after breast cancer may result in considerable financial burden. Their assessment is made more urgent because more women now participate in the workforce and because breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated wage losses, their determinants, and the associations between wage losses and changes for the worse in the family's financial situation among Canadian women over the first 12 months after diagnosis of early breast cancer. METHODS: We conducted a prospective cohort study among women with breast cancer from eight hospitals throughout the province of Quebec. Information that permitted the calculation of wage losses and information on potential determinants of wage losses were collected by three pretested telephone interviews conducted over the year following the start of treatment. Information on medical characteristics was obtained from medical records. The main outcome was the proportion of annual wages lost because of breast cancer. Multivariable analysis of variance using the general linear model was used to identify personal, medical, and employment characteristics associated with the proportion of wages lost. All statistical tests were two-sided. RESULTS: Among 962 eligible breast cancer patients, 800 completed all three interviews. Of these, 459 had a paying job during the month before diagnosis. On average, these working women lost 27% of their projected usual annual wages (median = 19%) after compensation received had been taken into account. Multivariable analysis showed that a higher percentage of lost wages was statistically significantly associated with a lower level of education (P(trend) = .0018), living 50 km or more from the hospital where surgery was performed (P = .070), lower social support (P = .012), having invasive disease (P = .086), receipt of chemotherapy (P < .001), self-employment (P < .001), shorter tenure in the job (P(trend) < .001), and part-time work (P < .001). CONCLUSION: Wage losses and their effects on financial situation constitute an important adverse consequence of breast cancer in Canada.

Quantitative exploration of possible reasons for the recent improvement in breast cancer survival.

OBJECTIVE: Breast cancer mortality has been declining in many countries including Canada because of improvements in survival. This study attempts to explain observed trends in breast cancer survival with special attention given to the role of improvements in early detection and treatment. METHODS: This study is based on 4,312 women diagnosed with primary invasive breast carcinoma treated in a Canadian breast center between 1976 and 2000 and followed to the end of 2001. Observed and relative survival rates were calculated. Multivariate relative survival regression models were used to assess trends in breast cancer survival over the study period. RESULTS: The proportion of women with small tumors (< or = 10 mm) was higher in late 1990s, while that of women with regional involvement was lower compared to earlier periods. Adjuvant chemotherapy or endocrine therapy use increased steadily from 6.6% to 84.0% during the study period. Five-year relative survival rates ranged between 82.1% and 83.7% between 1976 and 1990, and increased thereafter to reach 87.6% in 1991-95, and 92.1% in 1996-2000. During the first five years after diagnosis, women diagnosed in 1991-95 and 1996-2000 experienced a reduction in breast cancer mortality of 28% (Relative Risk (RR)= 0.72; 95% CI: 0.59-0.89) and 49% (RR = 0.51; 95% CI: 0.39-0.68) respectively compared to women diagnosed in 1976-90. Improvement in breast cancer survival in 1990's could not be explained by characteristics of women, biology of the tumor, advancements in early detection and type of initial treatments. CONCLUSION: A substantial increase in breast cancer survival was observed in the 1990s but the reasons for this improvement remain elusive. Better knowledge of these reasons could help not only to further reduce the burden related to breast cancer but also the burden related to other major cancer sites.

Provider's volume and quality of breast cancer detection and treatment.

For many health conditions, the process or result of medical procedures improves with increasing caseload. The evidence about breast cancer has not been thoroughly assessed. This review synthesizes the literature about provider's volume and performance in either breast cancer screening with mammography or treatment. Articles published in English between 1990 and 2006 were identified by a computerized search and by review of reference lists. In screening with mammography, the reading volume of the radiologist and the screening volume of the facility influence different components of performance. The most conclusive evidence for breast cancer treatment concerns the association between the surgeon's caseload and the process or end-results of therapeutic interventions. Although the mechanisms of these associations still need to be clarified, large provider's volume in screening mammography or breast cancer treatment is often related to the quality of medical interventions.

Influence of insulin-like growth factors on the strength of the relation of vitamin D and calcium intakes to mammographic breast density.

Diets with higher vitamin D and calcium contents were found associated with lower mammographic breast density and breast cancer risk in premenopausal women. Because laboratory studies suggest that the actions of vitamin D, calcium, insulin-like growth factor (IGF)-I, and IGF-binding protein-3 (IGFBP-3) on human breast cancer cells are interrelated, we examined whether IGF-I and IGFBP-3 levels could affect the strength of the association of vitamin D and calcium intakes with breast density. Among 771 premenopausal women, breast density was measured by a computer-assisted method, vitamin D and calcium intakes by a food frequency questionnaire, and levels of plasma IGF-I and IGFBP-3 by ELISA methods. Multivariate linear regression models were used to examine the associations and the interactions. The negative associations of vitamin D or calcium intakes with breast density were stronger among women with IGF-I levels above the median (beta = -2.8, P = 0.002 and beta = -2.5, P = 0.002, respectively) compared with those with IGF-I levels below or equal to the median (beta = -0.8, P = 0.38 and beta = -1.1, P = 0.21; P(interaction) = 0.09 and 0.16, respectively). Similar results were observed within levels of IGFBP-3 (P(interaction) = 0.06 and 0.03, respectively). This is the first study to report that the negative relation of vitamin D and calcium intakes with breast density may be seen primarily among women with high IGF-I or high IGFBP-3 levels. Our findings suggest that the IGF axis should be taken into account when the effects of vitamin D and calcium on breast density (and perhaps breast cancer risk) are examined at least among premenopausal women.

Levels of C-peptide and mammographic breast density.

Members of the insulin-like growth factor family have been associated with breast cancer risk and mammographic breast density, one of the strongest known breast cancer risk indicators. The aim of this cross-sectional study was to examine the association of levels of C-peptide (a marker of insulin secretion) with mammographic breast density among 1,499 healthy women recruited during screening mammography examinations. At time of mammography, blood samples and time since last meal were collected. Plasma C-peptide levels were measured by ELISA method, and mammographic breast density by a computer-assisted method. Spearman's partial correlation coefficients, adjusting for age and time since last meal (when necessary), were used to evaluate the associations. High body mass index and waist-to-hip ratio measurements were independently correlated with high levels of C-peptide (r(s) = 0.173 and r(s) = 0.252, respectively; P < 0.0001) or low breast density (r(s) = -0.389 and r(s) = -0.142, respectively; P < 0.0001). High levels of C-peptide were correlated with low breast density (r(s) = -0.210, P < 0.0001). However, the strength of the negative correlation was substantially reduced and was no longer significant after further adjustment for body mass index and waist-to-hip ratio (r(s) = -0.022, P = 0.41). These results suggest that C-peptide levels are not associated with breast density after complete adjustment for adiposity. Thus, the insulin/C-peptide-breast density relation does not seem to mirror the insulin/C-peptide-breast cancer association.

Investigating the correlation between hospital of primary treatment and the survival of women with breast cancer.

BACKGROUND: To understand the relation between hospital of initial treatment and the survival of women with breast cancer, the authors investigated the characteristics of the treatment center that were related most to outcome. METHODS: The authors selected women from 5 regions of Quebec, Canada, who were diagnosed with lymph node-negative breast cancer between 1988 and 1994. Data were collected by chart review, queries to physicians, and linkage with administrative data bases. Overall survival to the end of 1999 was analyzed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The study population included 1727 women with a median follow-up of 6.8 years. The 7-year survival rate was 82% (95% confidence interval [95%CI], 80-84%). Compared with women who were treated in centers with > or = 100 new cases per year, the hazard ratio (HR) of death from any cause was 1.80 (95%CI, 1.23-2.63), 1.44 (95%CI, 1.03-2.03), and 1.30 (95%CI, 0.96-1.76) among women who were treated in hospitals with < 25 new cases, 25-49 new cases, and 50-99 new cases per year after adjusting for case mix and characteristics of the attending physician. However, the significance of caseload disappeared after adjusting for the type of hospital. By contrast, women who were treated in centers with either on-site radiotherapy, research activity, or teaching status had significantly better outcomes, even after adjusting for caseload (HR, 0.68; 95%CI, 0.50-0.92). These associations were independent of primary treatment received, which was a strong determinant of outcome. CONCLUSIONS: Primary treatment of early-stage breast cancer in larger hospitals was associated with improved survival. This relation was mediated by factors related to proficiency of care, which tended to cluster within institutions.

Vitamin D and calcium intakes from food or supplements and mammographic breast density.

BACKGROUND: A better understanding of factors that affect breast density, one of the strongest breast cancer risk indicators, may provide important clues about breast cancer etiology and prevention. This study evaluates the association of vitamin D and calcium, from food and/or supplements, to breast density in premenopausal and postmenopausal women separately. METHODS: A total of 777 premenopausal and 783 post-menopausal women recruited at two radiology clinics in Quebec City, Canada, in 2001 to 2002, completed a food frequency questionnaire to assess vitamin D and calcium. Breast density from screening mammograms was assessed using a computer-assisted method. Associations between vitamin D or calcium and breast density were evaluated using linear regression models. Adjusted means in breast density were assessed according to the combined daily intakes of the two nutrients using generalized linear models. RESULTS: In premenopausal women, total intakes of vitamin D and calcium were inversely related to breast density (beta = -1.4; P = 0.004 for vitamin D; beta = -0.8; P = 0.0004 for calcium). In multivariate linear regression, simultaneous increments in daily total intakes of 400 IU vitamin D and 1,000 mg calcium were associated with an 8.5% (95% confidence interval, 1.8-15.1) lower mean breast density. The negative association between dietary vitamin D intake and breast density tended to be stronger at higher levels of calcium intake and vice versa. Among postmenopausal women, intakes of vitamin D and calcium were not associated with breast density. CONCLUSION: These findings show that higher intakes of vitamin D and calcium from food and supplements are related to lower levels of breast density among premenopausal women. They suggest that increasing intakes of vitamin D and calcium may represent a safe and inexpensive strategy for breast cancer prevention.

Insulin-like growth factor-I, IGF-binding protein-3, and mammographic breast density.

Some studies have suggested that insulin-like growth factor (IGF) pathway is related to premenopausal breast density, one of the strongest known breast cancer risk factors. This study was designed specifically to test the hypothesis that higher levels of IGF-I and lower levels of IGF-binding protein (IGFBP)-3 are associated with high mammographic breast density among premenopausal but not among postmenopausal women. A total of 783 premenopausal and 791 postmenopausal healthy women were recruited during screening mammography examinations. Blood samples were collected at the time of mammography, and plasma IGF-I and IGFBP-3 levels were measured by ELISA. Mammographic breast density was estimated using a computer-assisted method. Spearman's partial correlation coefficients (r(s)) were used to evaluate the associations. Adjusted mean breast density was assessed by joint levels of IGF-I and IGFBP-3 using generalized linear models. Among premenopausal women, high levels of IGF-I and low levels of IGFBP-3 were independently correlated with high breast density (r(s) = 0.083; P = 0.021 and r(s) = -0.124; P = 0.0005, respectively). Correlation of IGF-I with breast density was stronger among women in the lowest tertile of IGFBP-3 than among those in the highest tertile of IGFBP-3 (r(s) = 0.138; P = 0.027 and r(s) = -0.039; P = 0.530, respectively). In contrast, the correlation of IGFBP-3 with breast density was stronger among women in the highest tertile of IGF-I than among those in the lowest tertile of IGF-I (r(s) = -0.150; P = 0.016 and r(s) = -0.008; P = 0.904, respectively). Women in the combined top tertile of IGF-I and bottom tertile of IGFBP-3 had higher mean breast density than those in the combined bottom tertile of IGF-I and top tertile of IGFBP-3 (53.8% versus 40.9%; P = 0.014). No significant association was observed among postmenopausal women. Our findings confirm that IGF-I and IGFBP-3 are associated with breast density among premenopausal women. They provide additional support for the idea that, among premenopausal women, these growth factors may affect breast cancer risk, at least in part, through their influence on breast tissue morphology as reflected on mammogram.

Volume of screening mammography and performance in the Quebec population-based Breast Cancer Screening Program.

BACKGROUND: In the Quebec Breast Cancer Screening Program (Programme quebecois de depistage du cancer du sein [PQDCS]), radiologists' and facilities' volumes of screening mammography vary considerably. We examined the relation of screening-mammography volume to rates of breast cancer detection and false-positive readings in the PQDCS. METHODS: The study population included 307,314 asymptomatic women aged 50-69 years screened during 1998-2000. Breast cancer detection rates were analyzed by comparing all women with screening-detected breast cancer (n = 1709) and a 10% random sample of those without (n = 30,560). False-positive rates were analyzed by comparing the 3159 women with false-positive readings and the 27,401 others in the 10% random sample. Characteristics of participants, radiologists and facilities were obtained from the PQDCS information system. Data were analyzed by means of logistic regression. RESULTS: The rate of breast cancer detection appeared to be unrelated to the radiologist's screening-mammography volume but increased with the facility's screening-mammography volume. The breast cancer detection rate ratio for facilities performing 4000 or more screenings per year, compared with those performing fewer than 2000, was 1.28 (95% confidence interval [CI] 1.07-1.52). In contrast, the frequency of false-positive readings was unrelated to the facility's screening volume but was inversely related to the radiologist's screening volume: the rate ratio for readers of 1500 or more screenings per year compared with those reading fewer than 250 was 0.53 (95% CI 0.35-0.79). INTERPRETATION: Radiologists' and facilities' caseloads showed independent and complementary associations with performance of screening mammography in the PQDCS. Radiologists who worked in larger facilities and read more screening mammograms had higher breast cancer detection rates while maintaining lower false-positive rates.

Conceptualization and sources of costs from breast cancer: findings from patient and caregiver focus groups.

Assessment of economic burden of breast cancer to patient and family has generally been overlooked in assessing the impact of this disease. We explored economic aspects from the perspective of women and their caregivers. Focus groups were conducted in 3 Quebec cities representing urban and semi-urban settings: 3 with 26 women first treated for non-metastatic breast cancer in the past 18 months, and 3 with 24 primary caregivers. We purposefully selected participants with different characteristics likely to affect the nature or extent of costs. Thematic content analysis was conducted on verbatim transcripts. Costs of breast cancer could be substantial, but were not the most worrisome aspect of the illness during treatments. Some costs were considered unavoidable, others depended on ability to pay. Costs occurred over a long period, with long term impact, and were borne by the whole family and not just the woman. Principal cost sources discussed were those associated with accessing health care, wage losses, reorganization of everyday life, and coping with the disease. This study provided deeper understanding of cost dynamics and the experience of costs among Canadian women with non-metastatic breast cancer, whose treatment and medical follow-up costs are borne through a system of universal, publicly funded health care.

A population-based study of the impact of delaying radiotherapy after conservative surgery for breast cancer.

BACKGROUND: Practice guidelines have set a maximum waiting time to radiation therapy for breast cancer. We evaluated if delaying radiotherapy resulted in worse outcomes in a large cohort of women with node-negative breast cancer. METHODS: We selected a random sample of cases among women diagnosed with localized breast cancer in five regions of Québec, Canada, between 1988 and 1994. Only women with pathologically (n = 926) or clinically (n = 136) negative axillary nodes, and stage 1 or 2 disease treated with conservative surgery and radiotherapy were eligible. Information was obtained by chart review, queries to physicians and linkage with administrative databases. Outcomes were estimated by Kaplan-Meier method and Cox proportional hazards analysis. Median follow-up was 7.1 years (range: 0.9-11.8). RESULTS: Median delay to radiotherapy was 12.4 weeks in those who received chemotherapy and 8.4 weeks in others. Overall survival at 7 years was 85.6%. Local relapse-free and distant disease-free survivals were 77.6 and 76.2%. There was no significant difference in survival according to delay to radiotherapy in crude or multivariate analysis adjusting for several prognostic factors, including systemic treatment. The risk of local failure conditional on survival in women who received radiotherapy more than 12 weeks after surgery was increased (hazard ratio: 1.75, 95% confidence interval: 1.00, 3.08, p-value = 0.052). CONCLUSIONS: Although longer waiting time to radiotherapy may compromise local control, it does not influence survival at 7 years when other predictors of outcomes are taken into account. Well controlled studies are needed to confirm and better characterize this relationship.

Compliance with consensus recommendations for systemic therapy is associated with improved survival of women with node-negative breast cancer.

PURPOSE: The impact of consensus recommendations for systemic therapy on outcome of disease is unclear. We evaluated if compliance with guidelines for systemic adjuvant treatment is associated with improved survival of women with node-negative breast cancer. PATIENTS AND METHODS: The study population included women diagnosed with invasive node-negative breast cancer in Québec, Canada, in 1988 to 1989, 1991 to 1992, and 1993 to 1994. Information was collected by chart review, linkage with administrative databases, and queries to attending physicians. Guidelines from the 1992 St Gallen conference were used as standard of care. Survival was estimated by Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Among 1,541 women, 358 died before December 1999. Median follow-up was 6.8 years. Seven-year event-free and overall survivals were 66% and 81%, respectively. Survival was 88%, 84%, and 74% in women at minimal, moderate, or high risk of recurrence. Virtually all women at minimal risk were treated according to the consensus (98.4% of 370). In comparison, adjusted hazard ratios of death were 1.0 (95% CI, 0.6 to 1.7) and 2.3 (95% CI, 1.3 to 4.0) among women at moderate risk treated according to the consensus or not, respectively. Among women at high risk, adjusted hazard ratios of death were 2.0 (95% CI, 1.4 to 2.8) and 2.7 (95% CI, 1.9 to 3.9), respectively. Both risk category (P <.0005) and compliance with guidelines (P <.0005) were independent significant predictors of survival. CONCLUSION: Treatment according to consensus recommendations is associated with improved survival of women with breast cancer in the community. Promoting the adoption of guidelines for treatment is an effective strategy for disease control.