That recognised risk factors can explain past and present international differences in breast cancer incidence: misconceptions 5

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Abstract

Recent discussions on research priorities in the United States have revealed a widespread assumption that known risk factors entirely explain the historic international differences in rates of breast cancer. In fact, formal investigations of this question, both by modelling between-country differences and studies of migrants, indicate that an appreciable amount of the international differences in this disease remains unexplained. If this is not recognised, opportunities for research on breast cancer aetiology may be lost.

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Most cited references 18

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Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies.

T Key, P Appleby, I. Barnes … (2002)

Reproductive and hormonal factors are involved in the etiology of breast cancer, but there are only a few prospective studies on endogenous sex hormone levels and breast cancer risk. We reanalyzed the worldwide data from prospective studies to examine the relationship between the levels of endogenous sex hormones and breast cancer risk in postmenopausal women. We analyzed the individual data from nine prospective studies on 663 women who developed breast cancer and 1765 women who did not. None of the women was taking exogenous sex hormones when their blood was collected to determine hormone levels. The relative risks (RRs) for breast cancer associated with increasing hormone concentrations were estimated by conditional logistic regression on case-control sets matched within each study. Linear trends and heterogeneity of RRs were assessed by two-sided tests or chi-square tests, as appropriate. The risk for breast cancer increased statistically significantly with increasing concentrations of all sex hormones examined: total estradiol, free estradiol, non-sex hormone-binding globulin (SHBG)-bound estradiol (which comprises free and albumin-bound estradiol), estrone, estrone sulfate, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone. The RRs for women with increasing quintiles of estradiol concentrations, relative to the lowest quintile, were 1.42 (95% confidence interval [CI] = 1.04 to 1.95), 1.21 (95% CI = 0.89 to 1.66), 1.80 (95% CI = 1.33 to 2.43), and 2.00 (95% CI = 1.47 to 2.71; P(trend)<.001); the RRs for women with increasing quintiles of free estradiol were 1.38 (95% CI = 0.94 to 2.03), 1.84 (95% CI = 1.24 to 2.74), 2.24 (95% CI = 1.53 to 3.27), and 2.58 (95% CI = 1.76 to 3.78; P(trend)<.001). The magnitudes of risk associated with the other estrogens and with the androgens were similar. SHBG was associated with a decrease in breast cancer risk (P(trend) =.041). The increases in risk associated with increased levels of all sex hormones remained after subjects who were diagnosed with breast cancer within 2 years of blood collection were excluded from the analysis. Levels of endogenous sex hormones are strongly associated with breast cancer risk in postmenopausal women.

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Migration patterns and breast cancer risk in Asian-American women.

R G Ziegler, R Hoover, M Pike … (1993)

Breast cancer incidence rates have historically been 4-7 times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, breast cancer risk rises over several generations and approaches that among U.S. Whites. Our objective was to quantify breast cancer risks associated with the various migration patterns of Asian-American women. A population-based, case-control study of breast cancer among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, was conducted during 1983-1987 in San Francisco-Oakland, California, Los Angeles, California, and Oahu, Hawaii. We successfully interviewed 597 case subjects (70% of those eligible) and 966 control subjects (75%). A sixfold gradient in breast cancer risk by migration patterns was observed. Asian-American women born in the West had a breast cancer risk 60% higher than Asian-American women born in the East. Among those born in the West, risk was determined by whether their grandparents, especially grandmothers, were born in the East or the West. Asian-American women with three or four grandparents born in the West had a risk 50% higher than those with all grandparents born in the East. Among the Asian-American women born in the East, breast cancer risk was determined by whether their communities prior to migration were rural or urban and by the number of years subsequently lived in the West. Migrants from urban areas had a risk 30% higher than migrants from rural areas. Migrants who had lived in the West for a decade or longer had a risk 80% higher than more recent migrants. Risk was unrelated to age at migration for women migrating at ages less than 36 years. Ethnic-specific incidence rates of breast cancer in the migrating generation were clearly elevated above those in the countries of origin, while rates in Asian-Americans born in the West approximated the U.S. White rate. Exposure to Western lifestyles had a substantial impact on breast cancer risk in Asian migrants to the United States during their lifetime. There was no direct evidence of an especially susceptible period, during either menarche or early reproductive life. Because heterogeneity in breast cancer risk in these ethnic populations is similar to that in international comparisons and because analytic epidemiologic studies offer the opportunity to disentangle correlated exposures, this study should provide new insights into the etiology of breast cancer.

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Age at first birth and breast cancer risk.

B MACMAHON, P. Cole, T Lin … (1970)

An international collaborative study of breast cancer and reproductive experience has been carried out in 7 areas of the world. In all areas studied, a striking relation between age at first birth and breast cancer risk was observed. It is estimated that women having their first child when aged under 18 years have only about one-third the breast cancer risk of those whose first birth is delayed until the age of 35 years or more. Births after the first, even if they occur at an early age, have no, or very little, protective effect. The reduced risk of breast cancer in women having their first child at an early age explains the previously observed inverse relationship between total parity and breast cancer risk, since women having their first birth early tend to become ultimately of high parity. The association with age at first birth requires different kinds of etiological hypotheses from those that have been invoked in the past to explain the association between breast cancer risk and reproductive experience.

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Author and article information

Journal

Journal ID (nlm-ta): Br J Cancer

Journal ID (iso-abbrev): Br. J. Cancer

Title: British Journal of Cancer

Publisher: Nature Publishing Group

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Print): 24 July 2012

Publication date (Electronic): 24 July 2012

Volume: 107

Issue: 3

Pages: 408-410

Affiliations

[1 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD, USA

Author notes

[* ]E-mail: hooverr@ 123456mail.nih.gov

Article

Publisher Item ID: bjc2012134

DOI: 10.1038/bjc.2012.134

PMC ID: 3405203

PubMed ID: 22828656

SO-VID: 2050937b-be23-41a3-8e2a-c9ba0797fa94

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