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.     

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.     

Variability in breast cancer surgery training across Europe: An ESSO-EUSOMA international survey

BackgroundAt present there is a lack of standardization of training in breast cancer surgery across Europe. The aim of this survey was to assess current practice in Europe regarding training in breast cancer (BC) surgery.Material and methodsGeneral surgeons, surgical oncologists, gynecologist, and plastic surgeons in Europe were invited to participate in this bespoke survey including 19 questions.ResultsThe survey was sent to 3.000 surgical oncologists across Europe. A total of 671 physicians (387 general surgeons, 152 gynecologists, 126 surgical oncologist, 31 plastic surgeons) answered the survey (23% response rate). Four hundred and sixty-eight physicians devoted between 50% −100% of their job to treating breast cancer. 45% worked in a community/University hospital within a dedicated Breast Unit.Specific additional breast surgery training was not universal: 20% had undertaken an accredited breast fellowship, 30% in a Breast Unit as a trainee, 21% had done additional courses, masters or diploma and 8% had not done any additional training. The majority (61%) of respondents worked in Units treating >150 BC cases per year, while 26% of the responders treat >120 new primary cases per year, and 23% less than 50 new cases a year. Multivariate analysis showed that breast surgeons working in a Breast Unit and treating more than 50 cases/year significantly performed oncoplastic procedures.ConclusionThere is a great variability in breast cancer surgery training in Europe. It is imperative to develop quality standards for breast cancer surgery training to ensure that patients get standardized and certified surgical management regardless of the country in which they are treated.     

Comprehensive assessment of genetic variation of catechol-O-methyltransferase and breast cancer risk

Because catechol-O-methyltransferase (COMT) catalyzes the addition of methyl groups to stabilize catechol estrogens that may induce DNA damage, genetic variants could influence breast cancer risk. To comprehensively characterize genetic variation in this gene, we selected haplotype-tagging single nucleotide polymorphisms (htSNP) in COMT. A total of 11 htSNPs (including COMT Val(158)Met) were selected based on the resequencing and dense genotyping approach of the Breast and Prostate Cancer Cohort Consortium. htSNPs were genotyped in a population-based, case-control study in Poland (1,995 cases and 2,296 controls). Individual SNPs were not significantly associated with risk. Haplotypes were estimated using the expectation-maximization algorithm. Overall differences in the haplotype distribution between cases and controls were assessed using a global score test. The TGAG haplotype (frequent in 4.3% of controls), in a linkage disequilibrium (LD) block that included the 3' untranslated region (UTR) of COMT, was associated with breast cancer risk (odds ratio, 1.29; 95% confidence interval, 1.06-1.58) compared with the most common haplotype TGAA; however, the global test for haplotype associations was not significant (P = 0.09). Haplotypes in another LD block, which included COMT Val(158)Met, were not associated with breast cancer risk (global P = 0.76). Haplotype-breast cancer risk associations were not significantly modified by hormonally related risk factors, family history of breast cancer, or tumor characteristics. In summary, our data does not support a substantial overall association between COMT haplotypes and breast cancer. The suggestion of increased risk associated with a haplotype in the 3' UTR of COMT needs to be confirmed in independent study populations.     

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     

Ethnic variation in breast cancer survival: A review

Intercountry, as well as intracountry, survival comparisons have revealed some differences in breast cancer survival among various ethnic populations. Most of these differences are probably explained by factors related to socioeconomic status. However, the well documented survival advantage of Japanese patients compared to Caucasian patients remains unexplained. Some recent studies suggest an adverse prognostic effect for obesity. Although still inconclusive, these findings raise the possibility that the better survival of Japanese patients may be in part related to their lower mean body weight. An effect of the lower fat intake of the Japanese in explaining their breast cancer survival advantage has little support at present, but, like the obesity hypothesis, deserves further study.     

Intra-operative assessment of sentinel lymph nodes for breast cancer surgery: An update

Lymph node (LN) involvement is the strongest prognostic factor in operable breast cancer (BC). Therefore, accurate assessment of LN status is essential for management of BC patients. The introduction of sentinel LN approach reduced the need for extensive axillary surgery to achieve accurate staging. However, positive sentinel LN as determined on postoperative histological examination often leads to a second axillary operation to ensure an accurate staging and that positive non-sentinel LNs are removed. Although preoperative assessment of LN has improved significantly, its accuracy remains insufficient to avoid further axillary surgery and is not sufficient to predict the status of the LN. Therefore, intraoperative evaluation of the sentinel LN to determine the need for completing lymph node dissection in case of metastasis can provide an important approach to guide BC management decision making. This article reviews the techniques available and under development for intraoperative detection of sentinel LN metastasis in BC surgery. The key features of each technique are described in detail, emphasising the benefits offered by label-free optical techniques: minimal sample preparation, high spatial resolution, and immediate on-site implementation. Optical techniques have the potential to provide a cost-effective and accurate intraoperative platform for the assessment of SLN within the operating theatre.     

Ethnicity and variation in breast cancer incidence

A breast cancer case–control study in Atlanta and 5 counties of central New Jersey involving interviews with 960 white and 281 black cases younger than 54 years of age enabled assessment of reasons for the varying incidence rates among these 2 ethnic groups. Of interest was why rates of breast cancer are higher among older white women, a trend that is reversed among very young women (<40 years). Calculation of the prevalence of exposure to classic and speculative risk factors and associated relative risks enabled derivation of population attributable risks (PARs) for the various combinations of age and ethnic groups. A higher PAR was derived for older (40–54 years) white (62%) than black (54%) women, which appeared to account for the observed difference in incidence between the 2 ethnic groups. Most of the difference in PARs between older whites and blacks was accounted for by whites having fewer births, later ages at first birth and slightly higher risks associated with reproductive and menstrual factors. Consideration of only well-established breast cancer risk factors showed a PAR among older whites of 57%, an estimate comparable to those previously published. Slightly higher overall PARs were derived when analyses considered several speculative but modifiable risk factors, including years of use of oral contraceptives, body size and alcohol consumption. Many of the analyses among younger women (20–39 years) were limited by available numbers, but it appeared that very little disease occurrence in young black women was associated with the factors studied. Int. J. Cancer 73:349–355, 1997. Published 1997 Wiley-Liss, Inc.     

An assessment of current achievements in the systemic management of breast cancer

Summary Over the past twenty years, breast cancer has come to be much more commonly regarded and treated as a systemic disease. Conventional chemotherapy and endocrine therapy used according to schedules that are tolerable to patients are generally effective and often induce worthwhile responses; nevertheless, the responses in general have a median duration of less than a year, and these therapies are rarely if ever curative. Continued efforts to use available agents with mere modifications of schedule and intensity seem unlikely to substantially improve upon the modest success already achieved. Rather, we desperately need radically new schedules, new agents (especially non-myelosuppressive agents), and new approaches (e.g. monoclonal antibody targeting of drugs, toxins, or radionuclides, perhaps combined with tumor sensitizing agents such as heat). It is our hope that consideration of some of these issues will encourage others to be bolder in devising the next generation of clinical trials.     

Risk factors for breast cancer: epidemiological evidence from Japanese studies

Although our understanding of the etiology of breast cancer has improved, many well-known risk factors are not modifiable and present knowledge has proved insufficient to allow the disease to be overcome. Indeed, incidence and mortality among Japanese women have increased over the past three decades. Here, we review epidemiological evidence from our cohort and case-control studies among Japanese women in comparison with other published findings. Our studies confirm the important role of established factors derived primarily from Western populations, such as menstrual and reproductive factors, anthropometric factors, physical activity, and alcohol intake, in the development of breast cancer. In addition, we provide further evidence to better understand the role of traditional Japanese foods in the etiology of breast cancer. Our cohort study found that a higher intake of isoflavone and higher levels of plasma genistein, but not daidzein, were associated with a decreased risk of breast cancer. Our case-control studies reveal a dose-response pattern for these compounds; specifically, decreased risk as women move from "no" to "moderate" intake and leveling off thereafter. In addition, gene-environment interactions have been revealed in the effects of isoflavones. The evidence reviewed suggests that isoflavone has a protective effect against breast cancer in Asian populations. Conversely, our cohort study did not observe an inverse association between breast cancer risk and the intake of green tea and/or the plasma level of tea polyphenols, but we did find an association between increased risk and active and passive smoking. In conclusion, based on current knowledge, primary prevention according to individual lifestyle modification should focus on alcohol intake, weight control, physical activity, and tobacco smoking.     

Future possibilities in the prevention of breast cancer: Role of genetic variation in breast cancer prevention

Risk factors for breast cancer are related to endogenous hormonesand reproductive events. As such, traditional cancer prevention strategies arenot easily applicable. Tamoxifen and other selective estrogen receptormodulators (SERMs) offer a new preventive strategy for some high-risk women,but have not yet been shown to be efficacious for all women. New tools toidentify high-risk women are needed. One such tool is the development of amultigenic model of breast cancer susceptibility that can be used to screenwomen in order to identify those who carry a combination of alleles that putsthem at significantly increased risk.     

Taxanes in breast cancer: An update

Over the past decade the taxanes have proved to be fundamental in the treatment of breast cancer. Initially found to have efficacy in metastatic breast cancer, the taxanes are now vital components in the treatment of early-stage disease, in which their addition to adjuvant treatment of early breast cancer has been shown to improve overall survival. In addition, the taxanes have demonstrated a role in first-line therapy for metastatic disease, with some of the highest efficacy of any class of chemotherapy. Targeted therapies in combination with the taxanes have further improved survival for both early and metastatic disease. New formulations of taxanes may both improve antitumor activity and reduce toxicity.