Background
Breast cancer (BC) is the most common cancer diagnosis among Canadian and American women.1,2 Fortunately, since 1986, the BC mortality rate has decreased by 49%3 (Figure 1). The resultant gap between BC incidence and mortality represents an expected increase in the prevalence of BC survivors (BCS) in the population. Relative to the general population, BCS are subject to a persistent burden of negative financial, psychological, and physical sequelae; long-term risks of recurrence; and elevated risks of non-BC causes of death.4 An up-to-date estimate of the cumulative prevalence of BCS informs planning of adequate survivorship care services, including surveillance and screening, management of long-term treatment-related effects, health promotion, and care coordination.5
Trend over time in the gap between age-standardized breast cancer incidence and mortality rates. Since the peak mortality rate (43 per 100,000) in 1986, there has been a 48% growth in the gap between age-standardized incidence and mortality because of a 49% decrease in mortality by 2020.
Data from Brenner DR, Weir HK, Demers AA, et al. Projected estimates of cancer in Canada in 2020. CMAJ 2020;192:E199–205.
Citation: Journal of the National Comprehensive Cancer Network 20, 9; 10.6004/jnccn.2022.7028
In 2007, the Canadian Cancer Society published a special report on BC which estimated that in 2003, 1% of the Canadian population were BCS who had been diagnosed within the previous 15 years.6 In a subsequent 2015 publication, it was estimated that in 2009, 0.9% of women were BCS diagnosed in the previous 10 years. In 2019, the American Cancer Society (ACS) published an estimate that in 2015 there were approximately 3.86 million BCS in the United States (which has similar BC outcomes) who had been diagnosed since 1975.2 This statistic roughly corresponds to a prevalence of 2.9% of the American female population aged ≥18 years, with approximately 35% of these cases having been diagnosed >15 years prior. As a result of continued improvements in screening and systemic therapies, over the past 15 years, the mortality rate has improved an additional 26%3 but, to our knowledge, no recent updates of the prevalence of BCS have been published. The utility and value of an up-to-date estimate of BCS prevalence has also increased in the past decade due to substantial gains in the understanding of the long-term health effects of surviving a BC diagnosis and subsequent treatment.
The purpose of this analysis was to estimate the overall prevalence of BCS diagnosed since 2007 among Canadian women in 2022. Analyses were performed with and without consideration of death of other causes and to determine prevalence by current age group.
Methods
BC Incidence and Survival Data
We extracted the projected female BC case count for each age group from the Canadian Cancer Society’s published statistics reports from 2007 to 2021.1,6–19 Male cases of BC were not included because they represent <1% of total cases and have different survival statistics.1 Projected case counts were used to provide the most up-to-date estimate because reporting of complete actual case counts typically lags by 4 years. We also extracted the predicted age-standardized (ie, weighting for the age distribution of BC) net survival rates for 1, 5, and 10 years from the 2019 Canadian Cancer Statistics report,18 and we used the 15-year net survival rate published by the ACS.20 The years with unknown age-standardized net survival rates were interpolated by fitting a third-order polynomial to the known values (Table 1). We were only able to locate Canadian reports of survival rates for each age group for 5-year net survival.21 The age-specific survival for the remaining years was estimated following the same distribution of survival rates among the age groups relative to the rate for all ages.
Breast Cancer Survival Rates for 1 to 15 Years Since Diagnosis by 5-Year Age Groups
Although overall survival (OS) is an estimate of the chance of remaining alive some period of time after diagnosis, net survival attempts to isolate the effect of a cancer diagnosis on survival by removing competing noncancer causes of death over a period of time.22 The net survival rates were calculated using the Pohar Perme estimator23 from incidence data from the Canadian Cancer Registry linked to death information from the Canadian Vital Statistics Death Database. The expected survival probabilities were mostly obtained from sex-specific annual provincial life tables with adjustments for female BC-specific mortality rates in the general population according to age group and year of death.18 Net survival rates were predicted using the period method, which uses recent survival rates (in this case, from 2012 to 2014).24–26 Table 1 reports the net survival rates used, including the interpolated values.
Net survival is the most widely tracked survival statistic, but it implies that some of the women in our estimated case counts survived BC but died of other causes in the interim. Therefore, we also determined the prevalence using published OS rates from retrospective population-level analyses of BC in Ontario.27,28 Ontario is the most populous Canadian province (∼38% of Canada’s population) and has the same 5-year BC net survival rates as Canada overall.1 We used 1-year and 5-year OS reported by stage by Seung et al27 for diagnoses between 2012 and 2015, and 10-year OS reported for stages I–III by Abdel-Qadir et al28 for diagnoses from 2005 to 2015. Because of limited available data for stage IV BC diagnoses, the 10-year BC-specific survival of 12.8% from the United States was used for the approximately 4.9% of cases diagnosed as stage IV.29 Using the prevalence of each stage at diagnosis,17 the weighted average of 1-year, 5-year, and 10-year OS were calculated as 96.0%, 84.1%, and 67.5%, respectively. A second-order polynomial was fit to these data points to interpolate OS for the remaining years.
2022 Survival Case Counts
The patients within each 5-year age group for each year of diagnosis were multiplied by the net survival rate for the corresponding age group and corresponding length of time since diagnosis. The length of time between 2022 and the year of diagnosis was used to determine the current 5-year age group for surviving patients from that year. For example, patients diagnosed at age 45 to 49 years in 2007 were counted in the 60- to 64-year age group for their current age in 2022. For OS, total patients across all age groups from each year of diagnosis were multiplied by the corresponding OS rate for time since diagnosis to 2022. The number of survivors for net and OS were then summed for all 15 years of diagnoses.
Prevalence of BCS Among Canadian Women
We used the Statistics Canada data released on September 29, 2021, to determine the current number of living women within each 5-year age group.30 The prevalence of survivors was determined with net survival rates by dividing the surviving number of patients summed across all 15 years of diagnosis (2007–2021) by the number of women in that age group. For the sum of all ages together, the denominator was the sum of all women from age ≥20 years because there were no projected survivors in 2022 in the 15- to 19-year age group (cases were no longer projected in that age group after 2017). Prevalence estimates using OS were calculated using the sum of all ≥20-year age groups together.
Influence of Stage of Diagnosis
The published net survival rates are not specific to stage of BC, which is an important prognostic variable for survival.31 The only stage-specific survival reported by the Canadian Cancer Society is 5-year relative survival derived from a variety of sources, including other countries. To estimate the bias associated with our estimate of surviving cases without considering stage of diagnosis, we compared the estimates calculated using non–stage-specific and stage-specific 5-year net survival for 2017 cases surviving in 2022. The number of cases diagnosed at each stage (including unknown) in 2017 was estimated by multiplying the prevalence of each stage by the projected case count for each age group. The 2022 survivors for each stage were determined by multiplying the cases by the corresponding relative survival rate for each stage.32 The previously calculated non–stage-specific net survival case count was then adjusted for the expected number of cases with unknown stage for comparison with the stage-specific calculation.
Excess Heart Failure Hospitalization Costs for BC
The primary competing risk of death for BCS is considered cardiovascular diseases, primarily (76%) heart disease.33 As one example of many possible excess healthcare costs attributable to BC survivorship, we used Canada-specific data on excess heart failure hospitalizations experienced by BCS and their cost.28,34 We used the Abdel-Qadir et al28 Ontario population–based comparison of the 3-, 5-, and 10-year cumulative incidence of heart failure hospitalization for women diagnosed with early-stage BC between 2005 and 2015 and age-matched noncancer control subjects. The excess incidence was taken as the difference between the cumulative incidence for the 2 groups and was interpolated for the remaining years from 1 to 15 years since diagnosis using a logarithmic function best fitting the 3 data points. The number of heart failure hospitalizations was estimated by multiplying the number of net survival cases for all ages combined for each year of diagnosis from 2007 to 2021 by the excess cumulative incidence for the corresponding time since diagnosis. The number of heart failure hospitalizations per year of diagnosis was then multiplied by the average direct costs for heart failure hospitalization (in CAD) for the corresponding calendar year reported by Tran et al34 for Canada.
Results
Survival Rates and Prevalence of BCS
In the 15-year span from 2007 to 2021, there were 370,756 projected patients diagnosed with BC. Using age group–specific net survival rates, 318,429 (85.9%) of these patients were estimated to have survived BC by 2022. The distribution of survivors within current age groups is shown in Figure 2A; 86.2% of survivors are currently aged ≥55 years. Using net survival, the prevalence of BCS diagnosed in the past 15 years in 2022 is 2.1% of Canadian women. Figure 2B shows the prevalence by age group, which exponentially increases from 0.01% in the 20- to 24-year age group to 12.7% of those aged ≥90 years. Prevalence is 1.0% among the typical working and/or child-raising age group (20–64 years) and 5.4% among those aged ≥65 years. The incremental increase in prevalence based on recency of diagnosis for all ages combined was 0.8% and 1.5% of Canadian women diagnosed within the previous 5 and 10 years, respectively (Figure 2B, also showing age groups). Using non–age-specific OS, 277,194 (74.8%) of the 370,756 projected patients with BC would be survivors in 2022. The prevalence of overall BCS diagnosed within the past 15 years is 1.8% of Canadian women.
(A) Distribution of breast cancer survivors by current (2022) age group. (B) Prevalence of net survivors of breast cancer within Canadian population by current (2022) age group and time since diagnosis. Data labels are for prevalence with diagnosis within the past 15 years.
Citation: Journal of the National Comprehensive Cancer Network 20, 9; 10.6004/jnccn.2022.7028
Influence of Stage on Survival Estimates
In the stage-specific survival analysis for 2017 cases, 23,281 (89.6%) of 25,980 cases diagnosed with a known stage in 2017 were projected to survive to 2022. In comparison, using the net survival that does not consider stage of diagnosis, 23,016 (88.1%) cases were projected to survive to 2022. The effect of not considering stage at diagnosis in our primary analysis was an underestimation of the number of stage I/II survivors and overestimation of stage III/IV survivors and, because of the greater prevalence of stages I and II diagnoses, an overall underestimation of 421 cases, or 1.8% (Figure 3).
Comparison of 2017 cases surviving in 2022 by stage at diagnosis calculated by using stage-specific and non–stage-specific 5-year net survival rates. Data labels are the total number of cases and the percentage of all known stages.
Citation: Journal of the National Comprehensive Cancer Network 20, 9; 10.6004/jnccn.2022.7028
Cost of Excess Heart Failure Hospitalization of BCS
Our estimates projected that among the 318,044 net survivors who were diagnosed from 2007 to 2021, 6,119 (1.9%) would experience heart failure hospitalizations by 2022, with projected costs of $66.5 million CAD. Of these hospitalizations among BCS, 1,521 (24.9%) would be in excess of those occurring in noncancer control subjects, with projected costs of $16.5 million CAD for these excess hospitalizations attributable to BC.
Discussion
This analysis estimates that, in 2022, after removing the effects of competing causes of death, 2.1% of Canadian women are BCS diagnosed within the past 15 years. The prevalence of BCS who have not died of other (non-BC) causes was estimated to be 1.8%. These estimates suggest that the prevalence of BCS has doubled and that the absolute number of cases is 2.5-fold greater than the number reported in 2007. BC is especially prevalent among women currently aged ≥65 years (5.4%), after which nearly 50% of lifetime healthcare expenditures occur.35 However, given the integral roles that women fulfill within the family unit and the economy, the 1.0% prevalence among Canadian women in the typical working and/or child-raising age group (20–64 years) is also impactful. In composite, these data illustrate a far-reaching effect of BC on Canadian society.
Although our estimates of BC prevalence were calculated using Canadian data, they may be generalizable to other high-income countries, such as the United States, the United Kingdom, and Australia, given that these countries have also seen substantial decreases in BC mortality rate since the mid- to late 1980s.36 Indeed, restricting the ACS’s estimate of BCS2 to diagnoses within 15 years would produce a similar estimate of 2.0% of American women. Likewise, the American estimate of the prevalence of BCS diagnosed since 1975 of 2.9% of the female population is likely generalizable to Canada. Ironically, the progress in treatment that is a primary contributor to the improvements in mortality rates within high-income countries37 is also a primary determinant of the increased burden of survivorship. Multimodal BC treatment results in direct multiorgan toxicity and indirect lifestyle toxicity that can have long-term health effects years after completion of treatment.38
Treatment of BC is associated with substantial costs, excluding personal or family costs from symptom management, loss of independence or work, loss of life, or incident healthcare costs related to other conditions that may be attributable to BC. A primary competing risk of death for BCS is heart disease.39 A SEER analysis of a cohort of >500,000 BCS diagnosed between 1973 and 2015 in the United States showed that currently >20% of BCS deaths are caused by cardiovascular disease, compared with <30% of deaths occurring as a result of the index cancer.33 The relative risk of death due to heart disease among BCS compared with the American population (adjusted for age, race, and sex) was reported to be approximately 2.2 within the first year after diagnosis and increased to nearly 6-fold greater at ≥10 years after diagnosis.33 We found that $16.5 million CAD or 24.9% of the total expected healthcare costs related to heart failure hospitalizations among BCS diagnosed within the past 15 years was attributable to BC. These findings can be generalized to other high-income countries such as the United States by a crude conversion using the per-person healthcare cost ratio, which is 1:2 for Canada to the United States. Extrapolating the $16.5 million excess costs for heart failure hospitalization attributed to BC in Canada to the 3.86 million survivors in the United States and doubling the estimated costs provides an estimate of $317 million USD (0.79 conversion of $400 million CAD) of excess US healthcare costs.
We used heart failure hospitalizations as a single illustrative example of the excess healthcare costs associated with BC survivorship, but many others exist. In addition to heart disease, excess deaths occurred among BCS due to cerebrovascular, Alzheimer’s, and liver diseases relative to the general population within the largest (n=754,270) and most recent (2000–2015) American population–based analysis of noncancer causes of death with 15 years of follow-up after a BC diagnosis.4 Presumedly, there would be substantial excess healthcare costs associated with these conditions that are in excess of those in the general population and therefore are attributable to BC as well. Furthermore, numerous other long-term impairments result from a BC diagnosis and subsequent treatment that have less impact on mortality but have significant impact on morbidity and additional excess healthcare costs. For example, arm morbidity (eg, lymphedema, loss of mobility, sensory disorders) persists in up to half of BCS 2 years after diagnosis.40 Cancer-related fatigue persists in one-third of BCS at 5 to 10 years after diagnosis.41 Cancer-related cognitive impairment has been noted on cognitive tests and functional MRI 10 to 20 years after completion of BC treatment.42,43 Clinically important depression, anxiety, or both can persist in 15% of women 5 years after BC diagnosis.44 Increased risk of osteoporosis occurs among those with premenopausal BC diagnoses (∼20% of cases)45 and hormone receptor–positive diagnoses (∼65% of cases)46 who receive aromatase inhibitor treatment.47 All of these impairments may substantially impact quality of life, social functioning, work performance and productivity, and ability to return to work after BC treatment.48–52 Although these impairments and their burden can be reduced with various medical, allied health (eg, physical or occupational therapy), and healthy lifestyle (eg, physical activity, weight loss) approaches, the appropriate screening and evaluation procedures must also be in place to first identify the impairments. The incidence of persistent long-term impairments and risks of noncancer mortality in the BC survivorship period identify an urgent need for enhanced survivorship care for this growing segment of the Canadian population.
Several potential factors may influence the accuracy of our prevalence estimation. First, our use of case count data from 2007 to 2021 would underestimate the true prevalence of BCS by limiting diagnoses to within the past 15 years. Second, as shown by our exploratory analyses on the influence of considering stage at the time of diagnosis, our non–stage-specific primary analysis would underestimate the true case count of survivors. Finally, our analyses did not consider other factors that may influence survival, such as comorbid conditions, socioeconomic status, receptor status, and other BC features, such as histologic grade. In composite, it is likely that our estimate of approximately 2% prevalence of BCS among Canadian women is conservative.
Conclusions
Approximately 2% of Canadian women in 2022 are BCS diagnosed within the past 15 years. As a single example of the excess healthcare costs imposed by BC, 24.9% of the $16.5 million in heart failure hospitalization costs experienced in this cohort of survivors is in excess of women without BC. Given the excess healthcare costs, potential for reduced contributions to the workforce, and reduced quality of life associated with long-term impairments and risk of excess non-BC death among BCS, enhanced survivorship care is warranted to provide services to this segment of the population.
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