IJE Advance Access published online on March 28, 2008
International Journal of Epidemiology, doi:10.1093/ije/dyn055
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hormone therapy and the rise and perhaps fall of US breast cancer incidence rates: critical reflections
Department of Society, Human Development and Health, Harvard School of Public Health, Kresge 717, 677 Huntington Avenue, Boston, MA 02115, USA.
E-mail: nkrieger{at}hsph.harvard.edu
 |
Abstract |
|---|
 Top Abstract References |
|---|
Background Results of the Women's Health Initiative (WHI) study—which to many unexpectedly showed that hormone therapy (HT) did not decrease and may in fact have elevated risk of cardiovascular disease, while also finding expected links between HT and breast cancer—have spurred critical reflection chiefly regarding the cardiovascular results. Suggesting similar scrutiny of cancer epidemiology is warranted are new studies linking the post-WHI drop in HT use to a substantial decline in breast cancer incidence and the implications of these findings for prior explanations of the rising rates of US breast cancer incidence during the 1980s.
Methods Literature search for review and research articles on temporal trends in US breast cancer incidence during the past 25 years, starting in the mid-1980s, when extant epidemiologic evidence had already indicated that HT increased risk of breast cancer.
Results Among the 21 articles identified, spanning from 1987 to 2007, nine included no mention of HT as a possible factor contributing to the steep rise in breast cancer incidence in the 1980s, seven included a minor mention and only five (one published in 2003, the others in 2006 and 2007) provided any substantive discussion of this issue—but only in relation to current trends and not the 1980 rise in breast cancer incidence.
Conclusion A critical appraisal of the epidemiologic literature highlights important gaps in explanations for breast cancer incidence trends and also how current and changing population patterns of disease distribution are ultimately what put our aetiologic explanations to the test.
Keywords Breast cancer, confounding, epidemiology, hormone therapy, incidence rates, secular trends
Accepted 23 October 2007
Routine acceptance of use of hormone therapy (HT) was shattered in 2002 by the results of the largest randomized clinical trial of HT, the ‘Women's Health Initiative’ (WHI).1 Conducted in a population of mainly healthy women in the United States, this trial found that HT did not decrease, and may in fact have elevated, risk of cardiovascular disease, and it also observed expected links between HT and breast cancer.1–3 Publication of the results triggered a dramatic and enduring drop in prescriptions and marketing of HT in the United States, with the decline in HT use exceeding 50% compared with the period prior to the WHI results (Table 1).4–13
|
The results of the WHI have led to much critical reflection and debate.2,3,14–22 At one level, controversies centre on the timing of HT administration for risk of coronary heart disease (CHD);16–22 none dispute the HT-breast cancer links. At another level, the WHI results have spurred discussion about problems of confounding in observational studies, complexities involved in the design and analysis of randomized clinical trials and the enormous difficulties in testing whether potentially plausible biological pathways elucidated by basic research actually do explain disease occurrence, let alone population distributions of disease.2,3,14–22 At issue is a core tension in scientific research: maintaining a deep humility and expansive curiosity about all that is unknown while simultaneously working to gain rigorously tested knowledge to acquire sufficient provisional certainty to guide action and interventions.2,23–26 Focusing on the cardiovascular findings, four key lessons proposed by Petitti14 are: ‘Lesson one: do not turn a blind eye to contradiction’ (i.e. allegedly different effects of estrogen in women vs men on risk of CHD); ‘Lesson two: do not be seduced by mechanism’ (since ‘we will never know all there is to mechanism. Mechanism is complex’); ‘Lesson three: suspend belief’ (i.e. a belief in the protective effects of HT led to ignoring the possible role of confounding) and ‘Lesson four: maintain skepticism’ (‘science doors that are closed have a way of reopening’, in this case about hypotheses regarding the cardiovascular protective effects of HT).
Is a critical reevaluation of cancer research likewise warranted in the aftermath of the WHI? New research linking the drop in HT use to a drop in breast cancer incidence27–33 suggests it is. Of relevance are not only the new debates about whether such a link might be causal27–34 but also—as important but thus far unconsidered—the urgent need to re-evaluate prior explanations for the notable rise of US breast cancer incidence in the 1980s.
Keeping in mind Petitti's caveats, the first point to note is that a link between HT and risk of breast cancer has been well-documented in the epidemiologic literature since the mid-1970s.2,35–44 Postulated mechanisms involve estrogen's role as promoter (rather than initiator) of breast epithelial tissue cell growth, and especially that of tumours that are estrogen receptor positive (ER+).35–44 Evidence indicates that HT preferentially increases risk of breast cancer among: older women (>50 years of age, partly as linked to menopausal status and duration of use), women with a lower body mass index, women with ER+ compared with ER– tumours, and, in the case of HT including both progestins and estrogen, lobular and ductal-lobular carcinomas.35–44
The WHI results prompted a new round of research on the implications of HT use for breast cancer risk, extending from beyond estimates of relative risk to the actual population burden of disease.2,27–33,45–49 Epidemiologic analyses published between 2002 and 2005, using data from the United States, Europe and Australia, estimated that HT might account for 10–25% of observed cases.45–48
Predictions are one thing; changes in actual incidence rates are another. Notably, four new studies using post-WHI US cancer registry data have yielded findings compatible with the predicted estimates. In November 2006, Clarke et al.27 reported that from 2001 to 2004, breast cancer incidence declined by 11% in California, including within Northern California, with use of HT among the Northern California population having declined by 68% during this same time period. Shortly thereafter, in December 2006, Ravdin et al.28 presented a study at the San Antonio Breast Cancer Conference, based on US Surveillance, Epidemiology and End Result (SEER) cancer registry data from nine different US SEER registries, showing that US breast cancer incidence declined by 7% in 2003 (compared with rates in 2002) and by 12% among women age 50 and older with estrogen receptor positive (ER+) tumours.
Subsequently, in a paper published in April 2007, Ravdin et al.29 extended the analyses to include the 2004 breast cancer incidence data. They found ‘little change in breast-cancer incidence between 2003 and 2004’, and further reported that, comparing the 2004 with 2001 breast cancer incidence rates for women ages 50–69, ‘the decrease was more evident in those with estrogen-receptor-positive tumours (14.7%; 95% CI 11.6–17.4) than in those with estrogen-receptor-negative tumours (1.7%; 95% CI –4.6 to 8.0)’.29 Noting an absence of similar declines for other cancer sites, Ravdin et al.28,29 have speculated the breast cancer incidence decline was due to the drop in HT use subsequent to the release of the WHI results. Two subsequent US studies, one focused on the nine oldest SEER registries,30 the other on US state cancer registries,31 have yielded comparable results. European studies have also begun to report similar findings.32,33 Building on these findings, in August 2007 a study on the population attributable impact of HT use on breast cancer incidence in the United States estimated that ‘the number of breast cancers related to EP use (i.e. combined estrogen and progestin HT) could be on the order of hundreds of thousands, particularly given the elevated breast cancer risks and expanding prevalence of long-term users as time went on. For example, over the 7.5 year period between approval of Prempro and the WHI announcement (i.e. 1995 to mid-2002), over 127 000 breast cancer diagnoses could be related to EP, assuming a prevalence of EP use of 17.5% for women aged 50–79, and a relative risk of 2.0’.49
The rapidity and magnitude of the reported breast cancer incidence decline not surprisingly invite scientific skepticism regarding a cause-effect relationship,27–34 especially given research indicating that breast tumours have an estimated doubling time of 50–100 days and require 30–35 doublings before attaining a clinically detectable size of 1 cm.50 Alternative explanations, mentioned by Ravdin et al.,28,29 could include declines in mammography rates, leading to reduced detection, and also potential inaccuracies in the cancer registry data. Four testable arguments countering these concerns include:
- The observed decline in the United States occurred uniquely for breast cancer across nine different geographic regions, implying that it was not an artefact due to errors in cancer registry reporting, as noted by Ravdin et al.28,29
- Women using or stopping use of HT, given their access to medical care, including mammography, and their greater health consciousness,51–56 would be more, rather than less, likely to see a physician concerning their HT use and to have a tumour detected compared with non-HT users, implying that diagnostic bias (if extant) would result in higher, not lower, breast cancer incidence rates, the opposite of what was observed.
- With regard to mammography, Ravdin et al.29 cited evidence of a slight decline—by 3.2%, between 2000 and 2003—in US mammography rates, arguing that it was too small to explain the observed drop in overall breast cancer incidence and also incompatible with the drop occurring only among the estrogen-receptor positive and not estrogen-receptor negative tumours. New data from the US National Health Interview Survey, moreover, not only underscore that the 2000–05 decline in mammography was modest (from 80.8 to 79.5% among women age 40 and older)57 but also indicate that among the reasons women age 50–69 gave for not getting a mammogram in the past 2 years, the one that exhibited the greatest increase was ‘too expensive/no insurance/cost’ (up from 9.4 to 12.0%). Since women with lower income typically have lower risk of breast cancer compared with higher income women,58,59 it follows that the disproportionate presence of this group among those not getting mammograms would further minimize the impact of reduced mammography rates on breast cancer incidence. The Clarke et al.27 study, moreover, observed a sharp drop in breast cancer incidence in Marin county, one of the wealthiest counties in the United States.
- The biological plausibility of the hypothesis: the posited mechanism, building on extant knowledge about hormonal tumour promoters,42–44,46,60,61 is that removal of exposure to HT among tumours whose growth was especially sensitive to HT would slow or stop their growth; whether these tumours are permanently stopped or simply growing more slowly (leading to diagnosis at a later date) remains unknown.29,34
By implication, however, if the hypothesis that curtailing HT use could quickly lead to a marked reduction in breast cancer incidence is correct, then conceivably the reverse could be true: a substantive rise in HT use should result in higher breast cancer incidence rates. Here consideration of the recent historical record is useful.
Figure 1 shows well-known trends in the age-specific incidence of invasive breast cancer among US white women from 1937 to 1939 to 2003, drawing on data from the First, Second and Third National Cancer Surveys and the more recent SEER data.62–67 Results are shown only for the white women because they are the group most likely to exhibit HT-related changes in breast cancer incidence, given extensive documentation that HT use in the United States, at least until 2002, was most common among more affluent, healthier and predominantly white women, i.e. women with access to medical care, who could afford HT, and who did not have contraindications against its use.2,51–56,68–72 The importance of presenting data solely on this group, rather than the total population, is indicated by Table 2, which shows the marked increase, between 1980 and 2005, and especially most recently, in the proportion of the SEER and US populations that were foreign-born (from 7.2 to 13.8% and from 6.2 to 12.4%, respectively) and of colour (from 19.9 to 30.1% and from 16.6 to 25.3%, respectively). Since breast cancer incidence rates are typically lower among both the US foreign-born population and populations of colour, compared with US-born white women,58,59 presenting data on the total population would potentially confound HT-related temporal trends in breast cancer incidence with demographic trends.
|
|
As Figure 1 shows, the age-specific incidence rates began rising especially quickly among women age 50 and older starting in the early 1980s. A new study has quantified the trends in the SEER data for 1975–2002 and reported that the largest increase among white women occurred between 1982 and 1987 among women aged 50 and older who had localized tumours, with the annual percent change equaling 9.9% (a magnitude significantly different from 0); in contrast, among this same group, the annual percent change for 1975–82 was only 0.9% (not significantly different from 0), for 1987–99 it was only 1.7% (significantly different from 0) and for 1999–2002 it was –1.9% (not significantly different from 0).73 This 9.9% annual percent change in the 1980s is noteworthy for two reasons. First, this annual percent increase is of the same order of magnitude as the currently observed drop in breast cancer incidence rates among women over age 50. Second, it occurred at a time when not only mammography rates were rising, as has been previously noted,74–76 but also when HT use was dramatically increasing, especially the combined estrogen-progestin formulations, following a period in the mid-1970s when use of HT dropped due to the growing evidence linking estrogen-only HT and endometrial cancer.2,9,19,77,78
Keeping these data in mind, it is useful to review how numerous epidemiologic studies and review articles have explained the marked rise in US breast cancer incidence rates that occurred chiefly among women age 50 and older starting in the early 1980s. Table 3 presents a summary of articles published since the mid-1980s that have focused on temporal trends in US breast cancer incidence over the last 25 years,30,31,73–76,79–93 noting that by the start of this period epidemiologic evidence had already indicated that HT increased risk of breast cancer.2,35–44 Among the 21 articles identified, spanning from 1987 to 2007, nine included no mention of HT as a possible factor contributing to the steep rise in breast cancer incidence in the 1980s,74–76,80–82,85,90,91 seven included a minor mention79,83,84,86,87,89,93 and only five (one published in 2003, the others in 2006 and 2007) provided any substantive discussion of this issue30,31,73,88,92—but only in relation to current trends and not the 1980 rise in breast cancer incidence. Moreover, among the 16 articles including either no or minor mention of HT, virtually all attributed the rapid rise in the 1980s chiefly if not solely to increased detection due to rising mammography rates, noting that the sharp rise was unlikely to be explained by the observed incremental rise of well-known risk factors (e.g. earlier age at menarche, later age at first childbirth).73–76,79,89,93
|
Only starting in 2003, and especially in 2006, after publication of the WHI results, over 30 years after the first evidence linking HT use and breast cancer,2,35–44 and more than a decade after the epidemiologic evidence on these links were considered to be sufficiently robust to be a cause for serious concern, outweighing any then-presumed cardiovascular benefits,38 did articles on US breast cancer trends begin to focus on HT use as a potentially important driver of population rates of breast cancer.30,31,73,88,92
In other words, the lessons Petitti has drawn based on the cardiovascular-HT research apply equally to breast cancer. The point is not that the mammography explanation for the rapid rise in breast cancer incidence rates in the 1980s was ‘wrong’: part of the rise was shown to be due to increased rates of mammography and increased detection.73–75,81–93 Nor is the point that use of HT is more important than the other known risk factors for breast cancer. Rather, the problem is that since the mid-1980s, when extant knowledge linked HT use to risk of breast cancer, epidemiologic articles on trends in breast cancer incidence tended to offer scant or no mention of HT as a meaningful contributor to breast cancer incidence rates. Moreover, it was not until after the actual incidence of breast cancer fell, post-WHI, that connections between current drops in population rates of HT use and current declines in breast cancer incidence rates began to receive widespread attention, among epidemiologists, clinicians and the public at large34—albeit without any parallel re-analysis of the 1980s rise in HT use and rise in breast cancer incidence.
At one level, the changing views in the breast cancer literature are not surprising: scientific research abounds with examples of old observations re-interpreted in the light of new hypotheses and new evidence23–26 (consider only the rethinking of ulcers and gastric cancer in relation to infection by Helicobacter Pylori25 (pp.39—97)94,95]. More disturbing is the possibility that scientific hypotheses were influenced by deeply held beliefs in the benefits of science.2,23 Specifically, the expectation of greater detection hence higher incidence due to the intervention of mammography was more in keeping with the beliefs and values of cancer control (even taking into account concerns about false positives) than the alternative of iatrogenic harm. The implication is that it is essential to maintain a critical awareness of how interventions framed as ‘medical advances’ can damage, not just improve, population health, especially when economic interests are at play,2 as recent concerns about the overhyping of benefits and minimization or suppression of risks of several major pharmaceutical products readily reveals.96
Another key lesson concerns the value of population data, including cancer registry data.97 Especially in this era of genomic research and increasingly molecularized epidemiology, the new data on breast cancer incidence trends underscore how current and changing population patterns of disease distribution are ultimately what put our aetiologic explanations to the test.26,98–102 Whether or not current knowledge and hypotheses about the biological mechanisms of breast cancer aetiology would predict a rapid and substantial drop in breast cancer incidence following marked reductions in HT use, we are confronted by the observed recent sharp decline. This drop calls for explanation. Between the Scylla of too much scientific skepticism and the Charybdis of too much scientific certainty—whether about observed population data, postulated mechanisms or methods—it will be necessary to navigate a course of research and action moored to actual trends in breast cancer incidence and cognizant of, but not stranded by, the inevitable limitations of scientific knowledge.
Conflict of interest: None declared.
KEY MESSAGES
|
|
References |
|---|
|
TopAbstractReferences |
|---|
1 Writing Group for the Women's Health Initiative Investigators. Risk and benefits of estrogen plus progestin in healthy postmenopausal women. Principal results from the Women's Health Initiative randomised controlled trial. JAMA (2002) 288:321–33.
2 Krieger N. Löwy I and the ‘Women, Hormones, and Cancer’ group. Hormone replacement therapy, cancer, controversies & women's health: historical, epidemiological, biological, clinical and advocacy perspectives. J Epidemiol Community Health (2005) 59:740–48.
3 Petitti DB. Hormone replacement therapy for prevention. More evidence, more pessimism. JAMA (2002) 288:99–101.
4 Ettinger B, Grady D, Tosteson AN, Pressman A, Macer JL. Effect of the Womens’ Health Initiative on women's decision to discontinue postmenopausal hormone therapy. Obstet Gynecol (2003) 102:1225–32.[CrossRef][Web of Science][Medline]
5 Hersh AL, Stefanick ML, Stafford RS. National use of postmenopausal hormone therapy: annual trends and response to recent evidence. JAMA (2004) 291:47–53.
6 Buist DS, Newton KM, Miglioretti DL, et al. Hormone therapy prescribing patterns in the United States. Obstet Gynecol (2004) 104:1042–50.[CrossRef][Web of Science][Medline]
7 Majumdar SR, Almasi EA, Stafford R. Promotion and prescribing of hormone therapy after report of harm by the Women's Health Initiative. JAMA (2004) 292:1983–88.
8 Haas JS, Kaplan CP, Gerstenberger EP, Kerlikowske K. Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results. Ann Intern Med (2004) 140:184–88.
9 Stefanick ML. Estrogens and progestins: background and history, trends in use, and guidelines and regimens approved by the US Food and Drug Administration. Am J Prev Med (2005) 118:64S–73S.
10 Udell JA, Fischer MA, Brookhart MA, Solomon DH, Choudhry NK. Effect of the Women's Health Initiative on osteoporosis therapy and expenditure in Medicaid. J Bone Miner Res (2006) 21:765–71.[CrossRef][Web of Science][Medline]
11 Kelly JP, Kaufman DW, Rosenberg L, Kelley K, Cooper SG, Mitchell AA. Use of postmenopausal hormone therapy since the Women's Health Initiative findings. Pharmacoepidemiol Drug Saf (2005) 14:837–42.[CrossRef][Web of Science][Medline]
12 Guay MP, Dragomir A, Pilon D, Moride Y, Perreault S. Changes in pattern of use, clinical characteristics and persistence rate of hormone replacement therapy among postmenopausal women after the WHI publication. Pharmocepidemiol Drug Saf (2007) 16:17–27.[CrossRef]
13 Wysowski DK, Governale LA. Use of menopausal hormones in the United States, 1992 through June, 2003. Pharmacoepidemiol Drug Saf (2005) 14:171–76.[CrossRef][Web of Science][Medline]
14 Petitti D. Commentary: hormone replacement therapy and coronary heart disease: four lessons. Int J Epidemiol (2004) 33:461–63.
15 Lawlor DA, Davey Smith G, Ebrahim S. Commentary: The hormone replacement-coronary heart disease conundrum: is this the death of observational epidemiology? Int J Epidemiol (2004) 33:464–67.
16 Barrett-Connor E. Commentary: observation versus intervention – what's different? Int J Epidemiol (2004) 33:457–59.
17 Stampfer M. Commentary: hormones and heart disease: do trials and observational studies address different questions? Int J Epidemiol (2004) 33:454–55.
18 Harman SM, Naftolin F, Brinton EA, Judelson DR. Is the estrogen controversy over? Deconstructing the Women's Health Initiative Study: a critical evaluation of the evidence. Ann NY Acad Sci (2005) 1052:43–56.[CrossRef][Web of Science][Medline]
19 Rossouw JE. Implications of recent clinical trials of postmenopausal hormone therapy for management of cardiovascular disease. Ann NY Acad Sci (2006) 1089:444–53.[CrossRef][Web of Science][Medline]
20 Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA (2007) 297:1465–77.
21 Barrett-Connor E. Hormones and heart disease in women: the timing hypothesis. Am J Epidemiol (2007) 166:506–10.
22 Manson JE, Bassuk SS. Invited commentary: hormone therapy and risk of coronary heart disease: why renew the focus on the early years of menopause? Am J Epidemiol (2007) 166:511–17.
23 Ziman J. Real Science: What it is, and What it Means (2000) Cambridge, UK: Cambridge University Press.
24 Fleck L. Genesis and Development of a Scientific Fact (1979) Chicago: University of Chicago Press. (1935).
25 Thargard P. How Scientists Explain Disease (1999) Princeton, NJ: Princeton University Press.
26 Krieger N. Theories for social epidemiology in the 21st century: an ecosocial perspective. Int J Epidemiol (2001) 30:668–77.
27 Clarke CA, Glaser SL, Uratsu CS, Selby JV, Kushi LH, Herrinton JL. Recent declines in hormone therapy utilization and breast cancer incidence: clinical and population-based evidence. J Clin Oncol (2006) 24:e49–50.
28 Ravdin PM, Cronin KA, Howlader N, Chlebowski RT, Berry DA. A sharp decrease in breast cancer incidence in the United States in 2003. Presented at: The 29th annual San Antonio Breast Cancer Symposium, December 14–17, 2006. Available at: http://www.sabcs.org. (Accessed June 13, 2007).
29 Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. New Engl J Med (2007) 356:1670–74.
30 Jemal A, Ward E, Thun MJ. Recent trends in breast cancer incidence rates by age and tumor characteristics among U.S. women. Breast Cancer Res (2007) 9:R28.[CrossRef][Medline]
31 Stewart SL, Sabatino SA, Foster SL, Richardson LC. Decline in breast cancer incidence – United States, 1999-2003. MMWR (2007) 56:549–53.[Medline]
32 Bouchardy C, Morabia A, Verkooijen HM, Fioretta G, Wespi Y, Schäfer P. Remarkable change in age-specific breast cancer incidence in the Swiss canton of Geneva and its possible relation with the use of hormone replacement therapy. BMC Cancer (2006) 6:78.[CrossRef][Medline]
33 Verkooijen HM, Koot VC, Fioretta G, et al. Hormone replacement therapy, mammography screening and changing age-specific incidence rates of breast cancer: an ecological study comparing two European populations. Breast Cancer Res Treat (2008) 107:389–95.[CrossRef][Web of Science][Medline]
34 McNeil C. Breast cancer decline mirrors fall in hormone use, spurs both debate and research. J Natl Cancer Inst (2007) 99:266–67.
35 Hoover R, Gray LA Sr, Cole P, MacMahon B. Menopausal estrogens and breast cancer. N Engl J Med (1976) 295:401–05.[Abstract]
36 Ross RK, Paganini-Hill A, Gerkins VR, et al. A case-control study of menopausal estrogen therapy and breast cancer. JAMA (1980) 243:1635–39.
37 Brinton LA, Hoover RM, Szklo M, Fraumeni JF. Menopausal estrogen use and risk of breast cancer. Cancer (1981) 47:2517–22.[CrossRef][Web of Science][Medline]
38 Rosenberg L. Hormone replacement therapy: the need for reconsideration. Am J Public Health (1993) 83:1670–73.
39 Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52705 women with breast cancer and 108411 women without breast cancer. Lancet (1997) 350:1047–59.[CrossRef][Web of Science][Medline]
40 International Agency for Research on Cancer. In: Hormonal Contraception and Post-Menopausal Hormone Therapy (1999) Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 72. Lyon: IARC.
41 Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA (2002) 288:872–81.
42 Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med (2006) 354:270–82.
43 Althuis MD, Fergenbaumm JH, Garcia-Closas M, Brinton LA, Madigan MP, Sherman ME. Etiology of hormone receptor-defined breast cancer: a systematic review of the literature. Cancer Epidemiol Biomarkers Prev (2004) 13:1558–68.
44 Hwang ES, Chew T, Shiboski S, Farren G, Benz CC, Wrensch M. Risk factors for estrogen receptor-positive breast cancer. Arch Surg (2005) 140:58–62.
45 Beral V. Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet (2003) 362:419–27.[CrossRef][Web of Science][Medline]
46 Bakken K, Alsaker E, Eggen AE, Lund E. Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study. Int J Cancer (2004) 112:130–34.[CrossRef][Web of Science][Medline]
47 Coombs NJ, Taylor R, Wilcken N, Boyages J. HRT and breast cancer: impact on population risk and incidence. Eur J Cancer (2005) 41:1755–81.
48 Coombs NJ, Taylor R, Wilcken N, Fiorica J, Boyages J. Hormone replacement therapy and breast cancer risk in California. Breast J (2005) 11:410–15.[CrossRef][Web of Science][Medline]
49 Clarke CA, Glaser SL. Declines in breast cancer after the WHI: apparent impact of hormone therapy. Cancer Causes Control (2007) 18:847–52.[CrossRef][Web of Science][Medline]
50 Dietel M, Lewis MA, Shapiro S. Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review. Hum Reprod (2005) 20:2052–60.
51 Friedman-Koss D, Crespo CJ, Bellantoni MF, Andersen RE. The relationship of race/ethnicity and social class to hormone replacement therapy: results from the Third National Health and Nutrition Examination Survey 1988-1994. Menopause (2002) 9:264–72.[CrossRef][Web of Science][Medline]
52 Keating NL, Cleary PD, Rossi AS, Zaslavsky AM, Ayanian JZ. Use of hormone replacement therapy by postmenopausal women in the United States. Ann Intern Med (1999) 103:545–53.
53 Marks NF, Shinberg DS. Socioeconomic status differences in hormone therapy. Am J Epidemiol (1998) 148:581–93.
54 Bartman BA, Moy E. Racial differences in estrogen use among middle-aged and older women. Womens Health Issues (1998) 8:32–44.[CrossRef][Web of Science][Medline]
55 Brett KM, Madans JH. Use of postmenopausal hormone replacement therapy: estimates from a nationally representative cohort study. Am J Epidemiol (1997) 145:536–45.
56 Matthews KA, Kuller LH, Wing RR, Mellahn EN, Plantinga P. Prior to use of estrogen replacement therapy, are users healthier than non-users? Am J Epidemiol (1996) 143:971–78.
57 Chagpar AB, McMasters KM. Trends in mammography and clinical breast examination: a population-based study. J Surg Res (2007) 140:214–19.[CrossRef][Web of Science][Medline]
58 Kelsey JL, Bernstein L. Epidemiology and prevention of breast cancer. Annu Rev Public Health (1996) 17:47–67.[CrossRef][Web of Science][Medline]
59 Krieger N, Chen JT, Waterman PD, Rehkopf DH, Yin R, Coull BA. Race/ethnicity and changing US socioeconomic gradients in breast cancer incidence: California and Massachusetts, 1978-2002. Cancer Causes Control (2006) 17:217–26.[CrossRef][Web of Science][Medline]
60 Bradlow HL, Sepkovic DW. Steroids as procarcinogenic agents. Ann NY Acad Sci (2004) 1028:216–32.[CrossRef][Web of Science][Medline]
61 Cordera F, Jordan VC. Steroid receptors and their role in the biology and control of breast cancer growth. Semin Oncol (2006) 33:631–41.[CrossRef][Web of Science][Medline]
62 Dorn HF, Cutler SJ. Morbidity from Cancer in the United States. Public Health Services Publication No. 418, 1955. [Published concurrently with Public. Health Rep (1955) 70:1–122].
63 National Cancer Institute. In: Third National Cancer Survey: Incidence Data. NCI Monograph 41. Bethesda, MD: National Institutes of Health, National Cancer Institute, 1975. DHEW Pub No. (NIH) 75–787.
64 Horm JW, Asire AJ, Young JL Yr, Pollack ES. SEER Program: Cancer Incidence and Mortality in the United States, 1973-81. Bethesda, MD: Biometry Branch, Division of Cancer Prevention and Control, National Cancer Institute, US Dept of Health and Human Services, 1984. NIH Pub No. 85–1837.
65 Ries LAG, Miller BA, Hankey BF, Kosary CL, Harras A, Edwards BK, eds. SEER Cancer Statistics Review, 1973-1991: Tables and Graphs. NIH Pub. No. 94-2789. Bethesda, MD: National Cancer Institute, 1994.
66 Ries LAG, Eisner MP, Kosary CL, et al, eds. SEER Cancer Statistics Review, 1975-2001 (2004) Bethesda, MD: National Cancer Institute.
67 Ries LAG, Harkins D, Krapcho M, et al, eds. SEER Cancer Statistics Review, 1975-2003 (2005) Bethesda, MD: National Cancer Institute.
68 Petitti DB, Perlman JA, Sidney S. Estrogens and mortality. New Engl J Med (1986) 315:131–32.[Medline]
69 Vandenbroucke JP. Postmenopausal oestrogen and cardioprotection. Lancet (1991) 337:1482–83.[Web of Science][Medline]
70 Hemminki E, Sihvo S. A review of postmenopausal hormone therapy recommendations: potential for selection bias. Obstet Gynecol (1993) 82:1021–28.[Web of Science][Medline]
71 Posthuma WFM, Westerndorp RGJ, Vandenbroucke JP. Cardioprotective effect of hormone replacement therapy in postmenopausal women: is the evidence biased? BMJ (1994) 308:1268–69.
72 Krieger N. Postmenopausal hormone therapy (letter). New Engl J Med (2003) 348:2363–64.
73 Smigal C, Jemal A, Ward E, et al. Trends in breast cancer by race and ethnicity: update 2006. CA Cancer J Clin (2006) 56:168–83.
74 Hankey BF, Miller B, Curtis R, Kosary C. Trends in breast cancer in younger women in contrast to older women. J Natl Cancer Inst Monographs (1994) 16:7–14.
75 Wun LM, Feuer EJ, Miller BA. Are increases in mammographic screening still a valid explanation for trends in breast cancer incidence in the United States? Cancer Causes Control (1995) 6:135–44.[CrossRef][Web of Science][Medline]
76 Chu KC, Tarone RE, Kessler LG, et al. Recent trends in US breast cancer incidence, survival, and mortality trends. J Natl Cancer Inst (1996) 88:1571–79.
77 Kennedy DL, Baum C, Forbes MB. Noncontraceptive estrogens and progestins: use patterns over time. Obstet Gynecol (1985) 65:441–46.[Web of Science][Medline]
78 Wysowski DK, Golden L, Burke L. Use of menopausal estrogens and medroxyprogesterone in the United States, 1982-1992. Obstet Gynecol (1995) 85:6–10.[CrossRef][Web of Science][Medline]
79 Devesa SS, Silverman DT, Young JL Jr, et al. Cancer incidence and mortality trends among whites in the United States, 1947-84. J Natl Cancer Inst (1987) 79:701–70.[Web of Science][Medline]
80 Tarone RE, Chu KC. Implications of birth cohort patterns in interpreting trends in breast cancer rates. J Natl Cancer Inst (1992) 84:1402–10.
81 Miller BA, Feuer EJ, Hankey BF. Recent incidence trends for breast cancer in women and the relevance of early detection: an update. CA Cancer J Clin (1993) 43:27–42.[Abstract]
82 Sondik EJ. Breast cancer trends: incidence, mortality, and survival. Cancer (1994) 74(3 Suppl):995–99.[CrossRef][Web of Science][Medline]
83 Devessa SS, Blot JW, Stone BJ, Miller BA, Tarone RE, Fraumeni JF Jr. Recent cancer trends in the United States. J Natl Cancer Inst (1995) 87:175–82.
84 King SE, Schottenfeld D. The ‘epidemic’ of breast cancer in the US – determining the factors. Oncology. (Willison Park) 1996;10:453–62;discussion (462, 464, 470–72).
85 Wingo PA, Ries LA, Rosenberg HM, Miller DS, Edwards BK. Cancer incidence and mortality: 1973-1995: a report card for the US. Cancer (1998) 82:1197–207.[CrossRef][Web of Science][Medline]
86 Howe HL, Wingo PA, Thun MJ, et al. Annual report to the Nation on the status of cancer (1973 through 1998), featuring cancers with recent increasing trends. J Natl Cancer Inst (2001) 93:824–42.
87 Weir HK, Thun MJ, Hankey BF, et al. Annual report to the Nation on the status of cancer, 1975-2000, featuring the uses of surveillance data for cancer prevention and control. J Natl Cancer Inst (2003) 95:1276–99.
88 Li CI, Daling JR, Malone KE. Incidence of invasive breast cancer by hormone receptor status from 1992 to 1998. J Clin Oncol (2003) 21:28–34.
89 Ghafoor A, Jemal A, Ward E, Cokkinides V, Smith R, Thun M. Trends in breast cancer by race and ethnicity. CA Cancer J Clin (2003) 53:342–355. Erratum in: CA Cancer J Clin 2004;54:181.
90 Nasserri K. Secular trends in the incidence of female breast cancer in the United States, 1973-1998. Breast J (2004) 10:129–35. Erratum in: Breast J 2004;10:380.[CrossRef][Medline]
91 Jatoi I, Anderson WF, Rao SR, Devesa SS. Breast cancer trends among black and white women in the United States. J Clin Oncol (2005) 23:7836–41.
92 Holford TR, Cronin KA, Mariotto AB, Feuer EJ. Changing patterns in breast cancer incidence trends. J Natl Cancer Inst Monographs (2006) 36:19–25.
93 Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer Statistics, 2007. CA Cancer J Clin (2007) 57:43–66.
94 Danesh J. Is Helicobacter pylori infection a cause of gastric neoplasia? In: Infections and Human Cancer—Newton R, Beral V, Weiss RA, eds. (Cancer Survey Vol. 33). Plainview, NY: Cold Spring Harbor Laboratory Press, 1999, pp. 263–89.
95 Leung WK. Helicobacter pylori and gastric neoplasia. In: Infection and Inflammation: Impacts on Oncogenesis—Dittmar T, Zaenker KS, Schmidt A, eds. (2006) Basel: Karger. 66–80.
96 Angell M. The Truth about Drug Companies: How they Deceive us and What to do About it. Rev. and updated. (2005) New York: Random House.
97 Glaser SL, Clarke CA, Gomez SL, O’Malley CD, Purdie DM, West DW. Cancer surveillance research: a vital subdiscipline of cancer epidemiology. Cancer Causes Control (2005) 16:1009–19.[CrossRef][Web of Science][Medline]
98 Hirsch A. Handbook of Geographical and Historical Pathology, Vol. I: Acute Infectious Diseases. (transl. C. Creighton). (1883) London: The New Sydenham Society. 1–6.
99 Morris JN. Uses of Epidemiology (1957) Edinburgh: E. & S. Livingston Ltd.
100 Krieger N. Epidemiology and the web of causation: has anyone seen the spider? Soc Sci Med (1994) 39:887–903.[CrossRef][Web of Science][Medline]
101 Krieger N. Defining and investigating social disparities in cancer: critical issues. Cancer Causes Control (2005) 16:5–14.[CrossRef][Web of Science][Medline]
102 Kunitz S. The Health of Populations: General Theories and Particular Realities (2006) Oxford: Oxford University Press.
103 Decennial census data: National Center for Health Statistics. In: Health, United States, 2006, with Chartbook on Trends in the Health of Americans (2006) Hyattsville, MD: US Dept of Health and Human Services. 127. Centers for Disease Control and Prevention, National Center for Health Statistics.
104 Intercensal population estimates: U.S. Census Bureau. Population estimates archives. Available at: http://www.census.gov/popest/archives/. (Accessed February 19, 2007).
105 US Census Bureau. US decennial census: 1990 and 2000 data; US American Community Survey: 2005 data. Available at: http://www.census.gov/. (Accessed June 14, 2007).
106 Minnesota Population Center. In: National Historical Geographic Information System: Pre-release Version 0.1. 1980 US decennial census data. Minneapolis, MN: University of Minnesota 2004. Available at: http://www.nhgis.org. (Accessed June 14, 2007).
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Paul Commentary: Hormone therapy and breast cancer incidence: did epidemiologists miss an effect on national trends? Int. J. Epidemiol., June 1, 2008; 37(3): 638 - 640. [Full Text] [PDF]
|
|
|
|
|
|
G. D. Smith 'Something funny seems to happen': J.B.S. Haldane and our chaotic, complex but understandable world Int. J. Epidemiol., June 1, 2008; 37(3): 423 - 426. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||