Our results, based on the SEER 13 Registry Database, indicate that between 1992 and 2005, US age-standardized breast cancer incidence rates rose between 1992 and 1999 and then declined, with the fall in rates driven exclusively by trends among White non-Hispanic women aged 50 years and older who both had ER-positive tumors and resided in high-income counties. No such trends were evident—regardless of county income level, ER status, or age—among the Black non-Hispanic women, the Hispanic women, or—where numbers were sufficient to conduct meaningful analyses—among the American Indian/Alaskan Native women. These findings are in accord with our a priori hypothesis that the social patterning of US breast cancer incidence declines would mirror those of US hormone therapy use, with the sharpest declines occurring among White non-Hispanic women aged 50 to 69 years who lived in high-income counties and had ER-positive tumors. Contrary to our expectation, however, the decline in breast cancer incidence rates that we observed commenced in 1999, preceding the July 2002 publication of the WHI results.
Consideration of both study limitations and strengths lends credence to our findings. First, the lack of socioeconomic data in US cancer registry records,41,42
combined with the aggregation of the SEER 13 Registry Database to the county level,27
meant that we were constrained to conduct county-level analyses, using only county-level income data. Despite well-known problems affecting analyses using only group-level (“ecologic”) data,43
research nevertheless indicates that similar patterns of socioeconomic inequities in health, including in cancer incidence, have been detected through use of socioeconomic measures at the county, census tract, household, and individual level.37,44–46
Second, offsetting concerns that results could be biased by racial/ethnic misclassification, a recent large multisite SEER validation study, based on
self-reported data among 13,538 cancer patients diagnosed between 1973–2001 in the SEER-National Longitudinal Mortality Study linked database,
reported that the
overall agreement was excellent on race (κ=0.90, 95% CI=0.88, 0.91)” and “moderate to substantial on Hispanic ethnicity (κ=0.61, 95% CI=0.58, 0.64).31(p177)
Although the SEER results31
suggest that misclassification of race/ethnicity among Hispanics could lead to underestimates of incidence rates for them, it is unlikely that such misclassification would be linked to hormone therapy use, and so would be unlikely to bias results. Finally, although it would have been ideal to have had access to a large, longitudinal, representative US study cohort with detailed data—for both the women in the study and the population from which they arose—on lifetime socioeconomic position, race/ethnicity, nativity, hormone therapy use and other breast cancer risk factors (e.g., reproductive history),24,47
to our knowledge no such database exists. This limitation is offset by the fact that our study had access to records spanning the period 1992 to 2005 for over 350000 cases and the catchment populations for 13 large US cancer registries, thereby enabling us to look meaningfully at patterns by age, socioeconomic position, race/ethnicity, and ER status.
Adding additional plausibility to our findings and their interpretation, literature addressing the observed recent declines in US, European, and Australian breast cancer incidence rates has discussed at length why evidence indicates that these secular trends are not explained by declines in breast cancer detection or changes in other risk factors (e.g., body mass index), and they likewise have not offered any other additional competing hypotheses or evidence to explain these declines.1–14,48–50
Concomitantly, US data provide strong evidence that before the WHI, hormone therapy use was substantially lower among women with fewer versus more socioeconomic resources, and also among US Black, Latina, and Asian women compared with White women.23,24,51,52
Moreover, research on the role of steroids—including hormone therapy—as breast cancer tumor promoters renders biologically plausible a short lag time between cessation of hormone therapy exposure and a decline in risk of developing a detectable incident breast cancer.3,53,54
It is not our purpose to repeat these discussions here. Instead, we would like to emphasize 3 new contributions that our analyses provide.
First, our inclusion of socioeconomic data, in conjunction with race/ethnicity, age, and ER status, revealed that the pattern of a recent rise and fall in US breast cancer incidence has been restricted solely to women who at time of diagnosis resided in a high-income county, were White, were aged 50 years and older, and had ER-positive tumors. These findings bolster the hypothesis that declines in hormone therapy use led to declines in breast cancer incidence among the sociodemographic groups of women most likely to be prescribed and to use hormone therapy, since no other hypotheses have been advanced that would explain the sociodemographic and tumor-type specificity of the incidence patterns we report. Additionally, the results underscore the insufficiency of conventional US racialized approaches to analyzing cancer and other health data in relation only to race/ethnicity55,56
; instead, joint information on socioeconomic resources and race/ethnicity is vital for correctly understanding disease distribution, including that of cancer.34,37,41,55,56
Second, by also including data on incidence rates of tumors with unknown ER status, our study newly indicates that estimates of declines in the incidence of ER-positive breast cancer based only on observed data are likely to be underestimates. This is because the observed, and especially older, ER-positive rates fail to include those cases with unknown ER status that would otherwise have been characterized as ER positive had the data been available. Indeed, on the basis of our previous research investigating the impact of imputing missing ER status on racial/ethnic and socioeconomic disparities in risk of ER-positive and ER-negative tumors, it is conceivable that rates of ER-positive breast cancer among White non-Hispanic women living in affluent areas in the early to mid-1990s (when a higher proportion of cases had ER status unknown) could have been underestimated by as much as 15%.32
The net implication is that the actual secular decline in breast cancer incidence among these women is larger than has been reported on the basis of the observed data.
Third, our results indicate that the lesser access to hormone therapy among women subjected to socioeconomic deprivation and among women of color, initially considered a problem before the WHI results were reported,23,24,51,52
may in fact have spared them iatrogenic increases in their breast cancer incidence rates. The magnitude of increases and declines in breast cancer incidence observed among women in those sectors of society who were most likely to have been exposed to hormone therapy in turn underscores the dangers of inadequately understood pharmacological manipulation of complex hormonal systems22,57–59
—a caution that ought be kept in mind when considering past and present proposals to prevent breast cancer by administering regimens of powerful hormones to healthy young women.60–63
Finally, one additional question highlighted by our results concerns why the decline in US breast cancer incidence rates—including those among women aged 50 to 69 years with ER-positive tumors who lived in high-income counties—began in 1999, before publication of the WHI results in 2002. Of note, our findings are in accord with those of other studies reporting that use of hormone therapy in the United States peaked in 1999 and 200016,17,21,48,64
and that US breast cancer incidence rates began to decline starting in the period 1999 to 2001,4,7,8,49
albeit with the rate of decline accelerating after the WHI study.3,6–8
Together, these findings lend credence to the hypothesis that the 1998 HERS results played more of a role than previously appreciated in reducing physicians’ willingness to prescribe—and women’s willingness to use—hormone therapy.4,16,17
Better understanding of why hormone therapy use peaked between 1999 and 2001, not only in the United States15,17,64
but also the United Kingdom,13
would be useful in preventing future iatrogenic illness; any such analysis will likely necessitate a longer-term historical perspective attuned to societal determinants of health.22,34,57,65,66