Our analysis shows a favorable temporal trend in CBC IR since 1985, a time period that corresponds to the widespread uptake of tamoxifen adjuvant therapy in the US after the results of the NATO trial in 1983.16,17
Moreover, CBC rates fell more than 3% per year after a first ER-positive breast cancer. There was no significant decrease in CBC incidence after a first ER-negative breast cancer.
Notably, CBC rates varied according to age at the first breast cancer diagnosis, demonstrating a bimodal pattern overall after a first ER-positive breast cancer with an overall decline in the rates of about 0.5% with each yearly increase in age. Early and late peak incidence rates for CBC near ages 30 and 70 years contrasted somewhat with the bimodal peaks for primary breast cancer near ages 50 and 70 years.18
These results are in agreement with recent registry-based reports in the US and Europe7,8,12,13
and disagree with earlier reports of a constant incidence rate of CBC of approximately 0.5% to 1% per year.10,11,19
Our results support and extend the previous analysis by Bernstein et al,7
which also found a downward temporal trend in CBC incidence in the US during 1984 to 1998. The current analysis expanded the follow-up by 8 years (through 2006) and included an examination of variation according to ER status for first breast cancers. A 30% decline in CBC incidence between 1980 and 2000 was also reported in Sweden,8
and preliminary data suggests an annual 3.5% decline in CBC during 1990 to 2001 in the California Cancer Registry9
(only part of that registry, San Francisco and Oakland, was included in the current analysis).
Our findings disagree with the interpretation by Kurian et al20
that there were no clear trends in CBC by hormone receptor status and calendar year from 1992 to 2004 in the SEER data. They did find some evidence of a decrease during the 1990s after a hormone receptor–positive cancer diagnosed age 50+, but the trend did not clearly continue into 2000 to 2004. There were two important differences in our methodologic approach that might explain the discrepancy. Firstly, we examined the patterns by year of the first cancer diagnosis rather than by the year of the CBC diagnosis, which was used by Kurian et al. We used the year of diagnosis of the first cancer as a proxy for treatment that has greater clinical utility. Furthermore, we examined trends in the IR, whereas Kurian et al analyzed the changes in the standard incidence ratios (ie, the patterns in the second cancer rates in relation to the patterns in the breast cancer rates in the general population). Other more minor differences include their use of 2 rather than 12 months as the cutoff period for CBC and use of progesterone receptor status also to define hormone receptor positive cancers.
In the Early Breast Cancer Trialists' Collaborative Group's analysis of 12 randomized trials, use of tamoxifen for approximately 5 years reduced CBC risk by 39% (95% CI, 0.27% to 0.50%) among women with ER-positive or ER-unknown breast cancer.21
Tamoxifen use was widely adopted in the US during the late 1980s after the NATO trial.16
Patterns of use are complicated though as they depend on age and stage at diagnosis as well as ER status and use is also correlated with receipt of chemotherapy,17,22
which can also prevent CBC if used premenopausally.16
Furthermore, in the early 2000s, use of aromatase inhibitors (AI) increased as results from the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial became available.23
Reports from the ATAC trial24
indicate 32% to 43% reductions in CBC incidence with primary, sequential, or extended AI treatment strategies compared to tamoxifen. All of these factors make it difficult to formally assess the correlation between hormone therapy trends and CBC IR. Nevertheless, the fact that the strongest declines in CBC incidence rates were within the first 5 years after diagnosis of an ER-positive tumor is consistent with current practice guidelines for 5 years of adjuvant endocrine therapy with tamoxifen and/or AIs after an incident ER-positive breast cancer.28,29
Long-term follow-up of the randomized trials shows that the period of greatest tamoxifen efficacy is during current use, although benefits continue at least up to 10 years.21
As well as adjuvant hormone therapies and chemotherapy, other factors, such as mammography screening and/or postmenopausal hormone-replacement therapy, may also have contributed to declining CBC trends, if they detect and/or promote indolent tumors less likely to be associated with CBC. Bernstein et al,7
however, found similar CBC rates after in situ and invasive first cancers.
Our study has the usual limitations of descriptive epidemiology with retrospective analysis, missing data, lack of individual-level risk factors, and nonstandardized definitions. Nonetheless, SEER's large-scale and population-based design, long-term follow-up, breast cancer laterality, and ER status provided a unique opportunity to assess temporal trends for CBC. Another major strength of the study was that CBC IR were examined according to age at and year of diagnosis of the first breast cancer with adjustment for potential confounding by time since diagnosis of the first breast cancer. Details of hormone treatment were not available in SEER, but our annual percentage declines of higher than 3% after ER-positive first cancers suggest an important role for the widespread usage of adjuvant therapies, especially hormone treatments.
In summary, our results show a favorable decrease in the order of 3% per year for CBC incidence in the US since 1985. This overall trend was largely driven by declining CBC rates after an ER-positive first breast cancer, possibly due to the widespread usage of adjuvant hormone therapies. Although this decline represents a notable success, CBC rates overall remain high especially after a first ER-negative breast cancer.