The international variation in breast cancer rates: An epidemiological assessment

Part of the international differences in breast cancer incidence rates can be explained by geographic variation in reproductive and other breast cancer risk factors. Age at menarche and age at onset of regular ovulatory menstrual cycles are two such factors; both vary across populations directly according to breast cancer risk, and both are acknowledged as breast cancer risk factors. Consideration of the body of evidence on these factors, as well as that on age at menopause, suggests that the cumulative frequency of ovulatory menstrual cycles is a critical determinant of breast cancer risk. Although age at first term pregnancy explains the majority of the protective effect of parity on breast cancer risk, two recent studies have demonstrated a small residual protective effect of increasing number of births. It appears that pregnancy hasparadoxical effects on breast cancer risk in terms of hormone production and metabolism. The initial effect is an increased risk associated with first trimester estrogen exposure. However, the hormonal consequences of completing the pregnancy counteract this negative effect of early pregnancy. The effect of body weight, a breast cancer risk factor for postmenopausal women, can be explained in terms of increased extraglandular conversion of androstenedione to estrone. Further evidence supporting a pathogenic role of estrogens in the development of breast cancer comes from international studies of endogenous hormones in populations with differing risks of breast cancer. These risk factors have been incorporated into a mathematical model which is based on the concept that breast tissue ages according to hormonal (primarily estrogen) exposure; this model closely predicts the incidence rates throughout the world.     

Ethnic differences in breast cancer incidence in England are due to differences in known risk factors for the disease: prospective study

Background:

In the United Kingdom, breast cancer incidence is lower in South Asian and Black women than in White women, but the extent to which this is due to known risk factors is unknown. In a large prospective study, we describe breast cancer incidence by ethnicity, before and after adjustment for known risk factors for the disease.

Methods:

Women were recruited into the Million Women Study in 1996–2001, when information on reproductive and lifestyle factors known to influence the risk of breast cancer was obtained. Ethnicity was determined from study questionnaires and hospital admission data. Cox regression models were used to calculate adjusted relative risks (RR) for incident breast cancer in South Asians and Blacks compared with Whites.

Results:

Analyses included 5877 South Asian, 4919 Black, and 1 038 144 White women in England. The prevalence of 8 out of the 9 risk factors for breast cancer examined, differed substantially by ethnicity (P<0.001 for each), such that South Asian and Black women were at a lower risk of the disease than White women. During 12.2 years of follow-up incident breast cancer occurred in 217 South Asians, 180 Blacks, and 45 191 Whites. As expected, breast cancer incidence was lower in South Asians (RR=0.82, 95% CI 0.72–0.94) and Blacks (RR=0.85, 0.73–0.98) than in Whites when the analyses were adjusted only for age and region of residence. However, after additional adjustment for the known risk factors for the disease, breast cancer incidence was similar to that of Whites, both in South Asians (0.95, 0.83–1.09) and in Blacks (0.91, 0.78–1.05).

Conclusion:

South Asian and Black women in England have lower incidence rates of breast cancer than White women, but this is largely, if not wholly, because of differences in known risk factors for the disease.     

Clinical and histological predictors of contralateral breast cancer

AIMS: Women previously treated for primary operable breast cancer are at increased risk of developing cancer in the contralateral breast. The purpose of this study was to assess the annual incidence of metachronous contralateral breast cancer (CBC) and to identify factors that predict for its development. METHODS: A retrospective study was performed on 3211 women aged 相似文献   

Decreased rates of advanced breast cancer due to mammography screening in The Netherlands

The effect of the implementation of the Dutch breast cancer screening programme during 1990-1997 on the incidence rates of breast cancer, particularly advanced breast cancer, was analysed according to stage at diagnosis in seven regions, where no screening took place before 1990. The Netherlands Cancer Registry provided detailed data on breast cancer incidence in 1989-1997 by tumour stage, age and region. Annual age-adjusted incidence rates of all breast cancers and advanced cancers, defined as large tumours T2+ with lymph node and/or distant metastases, were compared with rates in 1989. In general, breast cancer incidence rose strongly in the early 1990s, especially in the age category 50-69 years (estimated annual percentage change (EAPC) 4.25; 95% CI 1.70, 6.86). The increase was mainly due to the increase in small T1 cancers and ductal carcinoma in situ. However, in women aged 50-69, advanced cancer incidence rates showed a significant decline by 12.1% in 1997 compared with 1989 (EAPC -2.14, 95% CI -3.47, -0.80), followed by a breast cancer mortality reduction of similar size after approximately 2 years. We confirm that breast cancer screening initially leads to a temporary strong increase in the breast cancer incidence, which is followed by a significant decrease in advanced diseases in the women invited for screening. It is evident that breast cancer screening contributes to a reduction in advanced breast cancers and breast cancer mortality.     

Trends in the incidence rate and risk factors for breast cancer in Japan

The incidence rate of breast cancer in Japanrose more than two-fold from 1959–60 to 1983–87.To assess to what extent this increase canbe explained by changes in the prevalence offour major risk factors of breast cancer (i.e.age at menarche, age at first birth, ageat menopause, and parity), we estimated the probabilityof developing breast cancer based on the jointdistribution and relative risks of these four riskfactors. The age-specific incidence rate during 1959–60 reportedby the Miyagi Prefectural Cancer Registry was usedto estimate the baseline hazard rate for womenwithout the four risk factors in the sameage group. Assuming that the baseline hazard rateis constant during all periods, we calculated theexpected incidence rates during the periods of 1959–60,1962–64, 1968–71, 1973–77, 1978–81, and 1983–87 for eachage group. Large discrepancies were noted between theobserved and expected incidence rates during 1983–87 inall age groups. The change in the jointdistribution of the four risk factors accounted forless than 40% of the increase observed from1959–60 to 1983–87, suggesting the effects of otherpowerful risk factors.     

An international comparison of male and female breast cancer incidence rates

Global international trends in female breast cancer incidence have been described previously but no comparable analysis of male breast cancer incidence rates has been conducted. We obtained male and female case and population data using Cancer Incidence in Five Continents (CI5). We calculated age‐adjusted, sex‐specific incidence rates and female‐to‐male incidence rate ratios (FMIRRs) and compared trends of such for the period 1988–2002. This analysis included 8,681 male breast cancer cases and 1.14 million female breast cancer cases. The highest male incidence rate was observed in Israel at 1.24 per 100,000 man‐years, and the highest female incidence rate was observed in the United States at 90.7 per 100,000 woman‐years. The lowest incidence rates for males (0.16) and females (18.0) were observed in Thailand. In general, male breast cancer incidence trends were variable; a minority of countries displayed evidence for an increase. In contrast, female incidence rates have been increasing in a majority of countries. The Pearson correlation coefficient (r) for male and female breast cancer incidence rates by country during 1988–2002 was 0.69. Male breast cancer rates were generally less than 1 per 100,000 man‐years, in contrast to the much higher rates of female breast cancer, providing for an overall FMIRR of 122. The differences in both incidence rates and time trends between males and females may reflect sex differences in underlying risk factors, pathogenesis, and/or overdiagnosis. Conversely, the high correlation between male and female breast cancer incidences may indicate that both sexes share some common risk factors for breast cancer.     

Urinary androgens and tumor estrogen receptor as predictors of ovariectomy response and of survival in advanced breast cancer

Summary Estrogen receptor (ER) status and urinary androgen (A) concentration were simultaneously determined in 50 premenopausal patients submitted to bilateral ovariectomy for advanced carcinoma of the breast. When both the hormonal parameters were positive (ER+ A+), the response to castration was favorable in 87.5% of the cases, with a survival rate of 39% at 5 years. No patient responded to the therapy when both the parameters were negative (ER– A–); none of them was alive at 5 years. An intermediate response (more than 50%) and survival rate at 5 years (more than 20%) was obtained in the group of patients with at least one of the two parameters positive (ER+ A–, or ER– A+). These responses were independent of the topography of neoplastic localizations and the length of the disease-free interval.     

Evaluating local differences in breast cancer incidence rates: A census-based methodology (United States)

Objectives: We used readily accessible, existing data to assess whether or not geographic variation in breast cancer incidence rates in the San Francisco Bay Area was related to the unequal distribution of known breast cancer risk factors.Methods: Cancer registry and 1990 census block-group data were used to look at the associations between breast cancer incidence and known risk factors (including parity, urban/rural status, and socioeconomic indicators) in 25 California counties. Average annual age-adjusted invasive breast cancer incidence rates were calculated for the period 1988-1992, and adjusted morbidity ratios were computed.Results: While breast cancer incidence in Marin County was 9 percent higher than that of the other 24 counties combined (relative risk=1.09, 95 percent confidence interval=1.01-1.18), this increase appeared to be due to the unequal distribution of known risk factors. Block-groups that had a high level of any risk factor had higher incidence rates, regardless of geographic location. After multivariate adjustment, breast cancer incidence no longer differed between Marin and the other counties (adjusted morbidity ratio=1.02).Conclusions: The results suggest that the unequal distribution of known risk factors was responsible for Marin County's high breast cancer incidence rate.     

Menopausal estrogen use and the risk of breast cancer

Summary The relationship between the occurrence of female breast cancer and menopausal estrogen replacement was investigated in a population-based case-control study. One hundred and eighty-three white female residents of King County, Washington (ages 50–74) in whom breast cancer was diagnosed from July, 1977, through August, 1978, were interviewed with respect to reproductive and other factors, with emphasis on the use of estrogen-containing medication. For purposes of comparison, the same data were collected from 531 white female King County residents of the same ages without breast cancer. Use of menopausal estrogens was reported somewhat more commonly among controls than among cases (relative risk = 0.74, 95% confidence interval = 0.51–1.08) and some variation in proportions of users was present between different hysterectomy-oophorectomy subgroups. However, each of these differences could easily have been due to chance. No substantial trends in risk were apparent with increasing duration of use, time since first use, time since last use, or average dose. The findings suggest that in King County no important relationship exists between use of menopausal estrogens and the occurrence of breast cancer.     

Incidence trends of female breast cancer in Saskatchewan, 1932–1990

Summary Using a log-linear model, we examined the 59-year incidence trends (1932–1990) of breast cancer by age, sex, and birth cohort in Saskatchewan, Canada. The incidence of breast cancer showed a continuously increasing trend since the 1930s. The trend was age dependent — in general, the 60 years and older age group had greater increases in incidence rates than did younger age groups. The increase in incidence rates in the 45 years and older age group was consistent over time and the incidence rates for those younger than 45 years increased until the 1960s, with a decline in trend following the 1960s. Birth cohort was a significant factor in the incidence of breast cancer. The major birth cohort effect can be described for those born from 1852 to 1927 — in every age group breast cancer incidence increased as the birth years advanced. For those born after 1927, the incidence of breast cancer was unchanged as the birth cohort changed and was sustained at a high level. Whether this phenomenon suggests that the risk factors for breast cancer ceased to increase over time needs to be confirmed by further studies.     

Geographical variation in endocrine function and its relation to breast cancer incidence: Some general considerations

Abnormalities in endocrine function are not a determinant of risk of breast cancer within countries, and racial differences in this function do not explain geographical variation in risk. It is suggested that hormonal status is related to tumor growth rates and hence to age at diagnosis, recurrence rates after primary treatment, and survival. Such evidence as there is points in this direction, but it still remains to be finally established whether the disease runs a similar course in all countries when patients are standardised for factors known to affect prognosis.     

The molecular etiology of breast cancer: evidence from biomarkers of risk

Estrogens can become endogenous carcinogens via formation of catechol estrogen quinones, which react with DNA to form specific depurinating estrogen-DNA adducts. The mutations resulting from these adducts can lead to cell transformation and the initiation of breast cancer. Estrogen metabolites, conjugates and depurinating DNA adducts in urine samples from 46 healthy control women, 12 high-risk women and 17 women with breast cancer were analyzed. The estrogen metabolites, conjugates and depurinating DNA adducts were identified and quantified by using ultraperformance liquid chromatography/tandem mass spectrometry. The levels of the ratios of depurinating DNA adducts to their respective estrogen metabolites and conjugates were significantly higher in high-risk women (p < 0.001) and women with breast cancer (p < 0.001) than in control subjects. The high-risk and breast cancer groups were not significantly different (p = 0.62). After adjusting for patient characteristics, these ratios were still significantly associated with health status. Thus, the depurinating estrogen-DNA adducts are possible biomarkers for early detection of breast cancer risk and response to preventive treatment.     

Risk of second primary cancer after breast cancer treatment

Technological advances in both diagnosis and treatment of breast cancer lead to early detection and better treatment management. Consequently, the population of long‐term survivors is on the rise. The risk of developing second cancers among breast cancer survivors was shown to be higher than that for the general population. The aim of this work was to review the literature on the risk of second primary cancer (SPC) after breast irradiation. Pubmed search of population‐based studies on SPC after breast irradiation was conducted and the findings (in terms of Standardised Incidence Ratio) were collated and discussed. Several studies confirmed the link between breast tumour irradiation and risk of SPC, showing a small, but valid risk. There are, however, confounding factors that can either underestimate or overestimate risks: misclassification of tumour status, genetic inheritance, smoking, environmental factors, and the lack of accurate data in cancer registries. While isolating these potential triggers might be difficult, this approach would allow better discernability between radiotherapy‐related risks and those generated by other factors. It is also important to evaluate the current status of treatment‐related late effects and to lower such risks by minimising the dose delivered to normal tissues.     

Geographical variation in breast cancer survival rates for women diagnosed in England between 1992 and 1994

The 5-year relative survival rates of women diagnosed with breast cancer between 1992 and 1994 were compared among the 99 Health Authorities (1999 boundaries) of England. Substantial variation, with evidence of geographical clustering was observed. Part of this variation was explained by differences in deprivation between Health Authorities, in particular by the percentage of class IV and V households.British Journal of Cancer (2004) 90, 2153-2156. doi:10.1038/sj.bjc.6601812 www.bjcancer.com Published online 27 April 2004     

Incidence and risk factors associated with bilateral breast cancer in area with early age diagnosis but low incidence of primary breast cancer: analysis of 10-year longitudinal cohort in Taiwan

Summary This study aims to examine the incidence and risk factors of bilateral breast cancer in area with low incidence rate. A total of 120 and 1902 women with bilateral and unilateral breast cancers were enrolled; various factors, including those concerning their medical history and life style, were extracted. Using Kaplan–Meier method, we calculate the cumulative incidence of contralateral breast cancer. The results show as follows. The cumulative incidences of contralateral breast cancer at 1, 3, 5 years after diagnosis of first breast cancer were 1.15, 1.94, and 2.97%, respectively. The statistically significant risk factors included menopause (Hazard Ratio (HR) =1.56, (1.00–2.42)), invasive lobular carcinoma (HR=2.98, (1.35–6.56)), receiving chemotherapy (HR=2.21, (1.43–3.42)) and/or radiotherapy (HR=3.32, (2.19–5.05) and a protective factor was tamoxifen therapy (HR=0.5 (0.34–0.74). Size of the second occurred tumour (2.97 cm) tended to be smaller than the first one (3.58 cm) with borderline statistical significance (p=0.0731). Comparing to the existing data on Western countries, we find a higher risk for developing contralateral breast cancer in Taiwan where a low incidence of first breast cancer rate with early age diagnosis is noted. It suggests that first primary breast tumour with early age of onset and lobular carcinoma are found more likely to develop bilateral breast cancers.Tony Hsiu-Hsi Chen and King-Jen Chang equally contributed to this article.     

GREB1 is a critical regulator of hormone dependent breast cancer growth

Summary Background Estrogen plays a central role in breast cancer pathogenesis and many potent risk factors for the development of the disease can be explained in terms of increased lifetime exposure to estrogen. Although estrogen regulated genes have been identified, those critically involved in growth regulation remain elusive.Methods.  To identify candidate genes involved in estrogen stimulated breast cancer growth, DNA microarray based gene expression profiles were generated from three estrogen receptor α (ERα) positive breast cancer cell lines grown under multiple stimulatory and inhibitory conditions.Results  Only three genes were significantly induced by 17β-estradiol (E2) relative to control in all three cell lines: GREB1, stromal cell-derived factor 1 (SDF-1) and trefoil factor 1 (pS2). Quantitative real-time PCR assays confirmed that in all three cell lines, GREB1 was induced by E2, but not by the antiestrogens tamoxifen (TAM) or ICI 182,780. GREB1 expression level was strongly correlated with ERα positivity in 39 breast cancer cell lines of known ERα expression status. GREB1 induction by E2 was rapid (7.3 fold by 2 h for MCF-7) and mirrored the fraction of cells entering S-phase when released from an estrogen deprivation induced cell arrest. Suppression of GREB1 using siRNA blocked estrogen induced growth in MCF-7 cells and caused a paradoxical E2 induced growth inhibition.Conclusion  These data suggest that GREB1 is critically involved in the estrogen induced growth of breast cancer cells and has the potential of being a clinical marker for response to endocrine therapy as well as a potential therapeutic target.     

Relationship between breast cancer risk factors and mammographic breast density in the Fernald Community Cohort

Background:

We investigated associations of known breast cancer risk factors with breast density, a well-established and very strong predictor of breast cancer risk.

Methods:

This nested case–control study included breast cancer-free women, 265 with high and 860 with low breast density. Women were required to be 40–80 years old and should have a body mass index (BMI) <35 at the time of the index mammogram. Information on covariates was obtained from annual questionnaires.

Results:

In the overall analysis, breast density was inversely associated with BMI at mammogram (P for trend<0.001), and parity (P for trend=0.02) and positively associated with alcohol consumption (ever vs never: odds ratio 2.0, 95% confidence interval 1.4–2.8). Alcohol consumption was positively associated with density, and the association was stronger in women with a family history of breast cancer (P<0.001) and in women with hormone replacement therapy (HRT) history (P<0.001). Parity was inversely associated with density in all subsets, except premenopausal women and women without a family history. The association of parity with density was stronger in women with HRT history (P<0.001).

Conclusion:

The associations of alcohol and parity with breast density appear to be in reverse direction, but stronger in women with a family history of breast cancer and women who ever used HRT.     

Alcohol intake and risk of breast cancer defined by estrogen and progesterone receptor status--a meta-analysis of epidemiological studies

The association between alcohol consumption and an increased risk of breast cancer has been established. It is still unclear however, whether this relationship differs across the estrogen receptor (ER) and progesterone receptor (PR) tumors subtypes. To provide a quantitative assessment of the association between alcohol intake and the risk of ER-/PR-defined breast cancer, we conducted a meta-analysis of cohort and case-control studies. Studies were identified by a literature search of PubMed through April 20, 2007 and by searching the reference lists of relevant articles. Summarized risk estimates (REs) with 95% confidence intervals (CIs) were calculated using random-effects models. The summarized results of the meta-analysis comparing the highest versus the lowest consumption categories showed statistically significant higher risks of developing all ER+ (27%), all ER- (14%), ER+PR+ (22%) and ER+PR- (28%), but not ER-PR- tumors. The dose-response meta-analysis showed that an increase in alcohol consumption of 10 g of ethanol per day was associated with statistically significant increased risks for all ER+ (12%), all ER- (7%), ER+PR+ (11%) and ER+PR- (15%), but not ER-PR-. A statistically significant heterogeneity of the REs across all ER+ versus ER-PR- was observed (p(heterogeneity) = 0.02). The summarized results from studies with adjustment for postmenopausal hormone use, body mass index and family history of breast cancer were higher and statistically significantly different from those without. The observed positive associations with alcohol for ER+PR+ and ER+PR- tumors cannot be explained by estrogen-dependent pathway only. Further studies need to clarify the biological mechanisms.     

Relationship between estrogen receptors and risk factors of breast cancer in Japanese pre- and postmenopausal patients

Summary The relation between estrogen receptors (ER) in breast cancer and risk factors was studied in 456 Japanese patients. ER was shown to be positive in 55.3% (252/456) of patients. There was no difference in ER positivity between pre- and postmenopausal patients. In premenopausal patients, only the age at menarche and obesity showed some influence on the ER positivity of breast cancer. Among postmenopausal patients, on the contrary, ER(+) cancers were predominant in the patient groups that have been known to be higher in the risk of incidence of breast cancer. The factors included were the age at marriage, number of pregnancies, number of live children, and body weight. Of these, the body weight of patients was the strongest influence on the ER positivity in the postmenopausal patients. After excluding the effects of body weight, some of the reproductive factors such as number of pregnancies and number of live children were shown to be related to the ER status. These results may suggest the combination of lower incidence of breast cancer and lower percentage of ER(+) cancers in Japanese postmenopausal women as compared with the Western countries.