Reproductive factors and breast cancer risk in Palestine: A case control study

BackgroundEarly age at menarche, late age at menopause, and late age at first full-term pregnancy are linked to a modest increase in the risk of developing breast cancer (breast ca). This study aims to investigate the reproductive determinants of breast cancer among women in the West Bank of Palestine.A structured questionnaire was used to collect data in a case-control study (237 registered cases and 237 controls). A multivariate analysis model was used to adjust for the association between women’s reproductive factors and breast ca risk. This study was approved by Al Quds University Ethical Research Committee and the Ministry of Health research unit.ResultsIn the multivariate analysis, menarche after 13 years of age, use of oral contraceptives for more than two months, and hormonal contraceptives use significantly doubled the risk for breast ca (Adjusted Odds Ratio (AOR) = 2.03, 95 % CI: 1.21–4.37, p < 0.011 and AOR = 2.2, 95 % CI: 1.24–4.01, p = 0.008, respectively). Women who used hormone replacement therapy (HRT) were significantly associated with higher odds (5 folds) of having breast ca versus those who did not use them (AOR 5.02, 95 % CI: 1.93–13.06, p = 0.001). Similarly, nulliparous women showed 6 times the odds of breast ca compared with women with one or more children (p = 0.005). Also, parental consanguinity marriage (AOR 2.59, 95 % CI: 1.53–4.36, p = 0.001) and positive family history (AOR 3.88, 95 % CI: 2.19–6.87, p = 0.001) of the condition can be strong determinants for breast ca in this study.ConclusionThis study provides clear evidence that the use of reproductive hormones, whether as a birth control tool or for therapeutic purposes, must be rationalized worldwide and in Palestine in particular.     

Lack of association between prohibitin 3' untranslated region C-->T polymorphism and breast cancer in a Turkish population

The 3' untranslated region (3'UTR) of the prohibitin gene has a positive effect on arresting cell proliferation between G1 and S phases and inhibits DNA synthesis. A C-to-T transition within this region creates a variant that alters mRNA function and has been shown to be associated with an increased breast cancer risk among young North Americans who are under 50 years and have at least one first-degree relative with breast cancer. We carried out a population-based case-control study to assess whether this association exists in Turkish women. We examined 106 breast cancer patients and 154 healthy controls by PCR and restriction fragment length polymorphism analysis. In the prohibitin 3'UTR, we did not detect a difference in CT/TT genotype frequency (p = 0.694; odds ratio [OR], 1.106; 95% confidence intervals [CI], 0.659-1.86) or in C/T allele frequency (p = 0.850; OR, 1.043; 95% CI, 0.667-1.62) between the all breast cancer patients and the controls. The results did not change in subgroups defined by age or family history. Hence our results do not lend support to the hypothesis that this polymorphism contributes to risk of breast cancer. The prohibitin T variant is not associated with the risk of breast cancer in Turkish women.     

Genetic polymorphism of glutathione S-transferase P1 and breast cancer risk

To evaluate the potential association between the GSTP1 genotype and the development of breast cancer, a hospital based case-control study was conducted on Korean women. The study population consisted of 171 histologically confirmed incident breast cancer cases and 171 age-matched controls with no present or previous history of cancer. PCR-RFLP was used for the GSTP1 genotyping and statistical evaluations were performed using an unconditional logistic regression model. Postmenopausal women with the GSTP1 Val allele were found to have a reduced risk of breast cancer (OR = 0.3, 95 % CI = 0.10-0.74). A significant interaction was observed between the GSTP1 genotype and alcohol consumption (p for interaction = 0.01); compared with never-drinking women with Ile/Ile genotype, ever-drinking women with the GSTP1 Val allele had almost a three-fold risk of breast cancer (OR = 2.9, 95 % CI = 1.05-7.85), whereas never-drinking women with Val allele had half this risk (OR = 0.5, 95 % CI = 0.27-0.93). Our findings suggest that the GSTP1 polymorphism influences individual susceptibility to breast cancer in the Korean women and this effect may be modified by alcohol consumption.     

DNA methylation and breast tumor clinicopathological features: The Western New York Exposures and Breast Cancer (WEB) study

We evaluated the association between methylation of 9 genes, SCGB3A1, GSTP1, RARB, SYK, FHIT, CDKN2A, CCND2, BRCA1, and SFN in tumor samples from 720 breast cancer cases with clinicopathological features of the tumors and survival. Logistic regression was used to estimate odds ratios (OR) of methylation and Cox proportional hazards models to estimate hazard ratios (HR) between methylation and breast cancer related mortality. Estrogen receptor (ER) and progesterone receptor (PR) positivity were associated with increased SCGB3A1 methylation among pre- and post-menopausal cases. Among premenopausal women, compared with Stage 0 cases, cases of invasive cancer were more likely to have increased methylation of RARB (Stage I OR = 4.7, 95% CI: 1.1–19.0; Stage IIA/IIB OR = 9.7, 95% CI: 2.4–39.9; Stage III/IV OR = 5.6, 95% CI: 1.1–29.4) and lower methylation of FHIT (Stage I OR = 0.2, 95% CI: 0.1–0.9; Stage IIA/IIB OR = 0.2, 95% CI: 0.1–0.8; Stage III/IV OR = 0.6, 95% CI: 0.1–3.4). Among postmenopausal women, methylation of SYK was associated with increased tumor size (OR = 1.7, 95% CI: 1.0–2.7) and higher nuclear grade (OR = 2.0, 95% CI 1.2–3.6). Associations between methylation and breast cancer related mortality were observed among pre- but not post-menopausal women. Methylation of SCGB3A1 was associated with reduced risk of death from breast cancer (HR = 0.41, 95% CI: 0.17–0.99) as was BRCA1 (HR = 0.41, 95% CI: 0.16–0.97). CCND2 methylation was associated with increased risk of breast cancer mortality (HR = 3.4, 95% CI: 1.1–10.5). We observed differences in methylation associated with tumor characteristics; methylation of these genes was also associated with breast cancer survival among premenopausal cases. Understanding of the associations of DNA methylation with other clinicopathological features may have implications for prevention and treatment.     

The review of randomization in the Canadian National Breast Screening Study: Is the debate over?

The randomization procedure in the Canadian National Breast Screening Study (NBSS) is assessed in this issue (see pages 193 to 199) by Drs. John C. Bailar III and Brian MacMahon. They conclude that although there was ample opportunity for the randomization process to be subverted, no evidence of subversion was found. This is unlikely to allay all concerns about randomization, because there are still puzzling differences between the arms of the NBSS in a number of baseline variables. For example, the existence of prior health claims for breast cancer for women who entered the NBSS in Manitoba has raised the possibility that subversion occurred. Although the question may never be resolved, one lesion is clear: randomization in clinical trials should be managed in a manner that makes subversion impossible. As for the clinical implications of the NBSS for women in their 40s, physicians may now look to the results of randomized trials that have been published more recently. A meta-analysis of these results suggests that screening mammography reduces deaths from breast cancer among women in their 40s, but continued follow-up over the next few years will be needed to settle the debate.     

Plasma protein carbonyl levels and breast cancer risk

To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9-1.5; OR = 1.5, 95% CI = 1.2-2.0; OR = 1.6, 95% CI = 1.2-2.1, for the 2(nd), 3(rd) and 4(th) quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger (<50 years) and older women, more pronounced among women with higher physical activity levels (0.7 hrs/week for 4(th) quartile versus lowest quartile OR = 2.0, 95% CI = 1.4-3.0), higher alcohol consumption (> or = 15 grams/day for 4(th) quartile versus lowest quartile OR = 2.3, 95% CI = 1.1-4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6-4.4 for 4(th) quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F(2t)-isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2-2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.     

Association of polymorphisms in SULT1A1 and UGT1A1 Genes with breast cancer risk and phenotypes in Russian women

Estrogens are critical for breast cancer initiation and development. Sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) conjugate and inactivate both estrogens and their metabolites, thus preventing estrogen-mediated mitosis and mutagenesis. SULT1A1 and UGT1A1 genes are both polymorphic, and different alleles encode functionally different allozymes. We hypothesize that low activity alleles SULT1A1*2 and UGT1A1*28 are associated with the higher risk for breast cancer and more severe breast tumor phenotypes. We performed a case-control study, which included 119 women of Russian ancestry with breast cancer and 121 age-matched Russian female controls. We used PCR, followed by pyrosequencing to determine SULT1A1 and UGT1A1 genotypes. Our data showed that UGT1A1*28 allele was presented at a higher frequency than the wild type UGT1A1*1 allele in breast cancer patients as compared to controls (p = 0.002, OR = 1.79, CI 1.23-2.63). Consistently, the frequency of genotypes that contain the UGT1A1*28 allele in the homozygous or heterozygous state was greater than the frequency of the wild type UGT1A1*1/*1 genotype in breast cancer patients as compared to controls (p = 0.003, OR = 4.00, CI 1.49-11.11 and p = 0.014, OR = 2.04, CI 1.14-3.57, respectively). The group of individuals, carrying the UGT1A1*28 allele in the homo- or heterozygous state also presented larger breast tumors (>2 cm) as compared to the group with high enzymatic activity genotypes p = 0.011, OR = 3.44, CI 1.42-8.36). No association was observed between any of the SULT1A1 genotypes and breast cancer risk or phenotypes. Our data suggest that UGT1A1 but not SULT1A1 genotype might be important for breast cancer risk and phenotype in Russian women.     

Exposure to chemotherapeutic agents and the risk of a second breast cancer: preliminary findings

Chemotherapeutic treatment for cancer has been successful in prolonging survival but may also lead to the development of second cancers. Two case-control studies presented here suggest, however, that breast cancer patients who receive chemotherapy are at significantly lower risk of a contralateral breast cancer than those who do not. Approximately 300 incident cases of contralateral breast cancer and 300 randomly chosen surviving controls with unilateral breast cancer were identified through the Connecticut Tumor Registry for inclusion in each study. The initial study was based on review of medical records at eight hospitals and indicated that the overall association with chemotherapy was modified by body build. The second study obtained information from in-person interviews, hospital records, and outpatient chemotherapy records from across the state. The preliminary results of this second study confirm the previous findings. Both cytotoxic and hormonal drugs were associated with a reduction in the risk of second breast cancers (OR = 0.5, 95 percent CI: 0.3-1.0; OR = 0.5, 95 percent CI: 0.2-1.2, respectively). Significant interaction with body build was observed for hormonal treatment (ratio of ORs = 5.8, 95 percent CI: 1.0-34.3 for a five-unit change in Quetelet's index), with a nonsignificant but detrimental effect suggested for overweight women (OR = 2.3, 95 percent CI: 0.4-13.9 for a Quetelet's score of 35).     

Associations of ionizing radiation and breast cancer-related serum hormone and growth factor levels in cancer-free female A-bomb survivors

Levels of exposure to ionizing radiation are increasing for women worldwide due to the widespread use of CT and other radiologic diagnostic modalities. Exposure to ionizing radiation as well as increased levels of estradiol and other sex hormones are acknowledged breast cancer risk factors, but the effects of whole-body radiation on serum hormone levels in cancer-free women are unknown. This study examined whether ionizing radiation exposure is associated with levels of serum hormones and other markers that may mediate radiation-associated breast cancer risk. Serum samples were measured from cancer-free women who attended biennial health examinations with a wide range of past radiation exposure levels (N = 412, ages 26-79). The women were selected as controls for separate case-control studies from a cohort of A-bomb survivors. Outcome measures included serum levels of total estradiol, bioavailable estradiol, testosterone, progesterone, prolactin, insulin-like growth factor-1 (IGF1), insulin-like growth factor-binding protein 3 (IGFBP-3), and ferritin. Relationships were assessed using repeated-measures regression models fitted with generalized estimating equations. Geometric mean serum levels of total estradiol and bioavailable estradiol increased with 1?Gy of radiation dose among samples collected from postmenopausal women (17%(1Gy), 95% CI: 1%-36% and 21%(1Gy), 95% CI: 4%-40%, respectively), while they decreased in samples collected from premenopausal women (-11%(1Gy), 95% CI: -20%-1% and -12%(1Gy), 95% CI: -20%- -2%, respectively). Interactions by menopausal status were significant (P = 0.003 and P < 0.001, respectively). Testosterone levels increased with radiation dose in postmenopausal samples (30.0%(1Gy), 95% CI: 13%-49%) while they marginally decreased in premenopausal samples (-10%(1Gy), 95% CI: -19%-0%) and the interaction by menopausal status was significant (P < 0.001). Serum levels of IGF1 increased linearly with radiation dose (11%(1Gy), 95% CI: 2%-18%) and there was a significant interaction by menopausal status (P = 0.014). Radiation-associated changes in serum levels of estradiol, bioavailable estradiol, testosterone and IGF1 were modified by menopausal status at the time of collection. No associations with radiation were observed in serum levels of progesterone, prolactin, IGFBP-3 or ferritin.     

Breast fine-needle aspiration malondialdehyde deoxyguanosine adduct in breast cancer

This study has analysed the generation of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adduct [M?dG], a biomarker of oxidative stress and lipid peroxidation, in breast fine-needle aspirate samples of 22 patients with breast cancer, at different clinical stages, in respect to 13 controls. The multivariate analysis show that M(1)dG adduct was higher in cases than in controls (Mean Ratio (MR) = 5.26, 95% CI = 3.16-8.77). Increased M?dG was observed in women with a tumour grade 3 and a pathological diameter 2 (MR = 7.61, 95% CI = 3.91-14.80 and MR = 5.75, 95% CI = 3.13-10.59, respectively). A trend with increasing tumour grade and pathological diameter was present (MR = 1.98, 95% CI = 1.57-2.50 and MR = 2.44, 95% CI = 1.71-3.48, respectively). Not significant effects of age and smoking habit were found (MR = 1.58, 95% CI = 0.92-2.72 and MR = 1.68, 95% CI 0.88-3.20, respectively). An increment over the background frequency of M?dG can contribute to breast cancer development. Increasing severity of breast tumour can influence DNA damage level.     

RAD51 polymorphisms and breast cancer risk

Breast cancer (BC) is one of the most common causes of death among women, and second in Iran. The objectives of this study were to determine the frequency of RAD51 G/C polymorphism in patients with breast cancer. We evaluated these polymorphisms and effects on the breast cancer risk association in a Iranian sporadic population-based case?Ccontrol study of 294 breast cancer cases and 315 controls using a PCR?CRFLP-based assay. Analyses of affected and controls show that homozygote genotype RAD51 GG has the highest frequency in both groups (33.3 in patients and 41.4 in control group). Genotype RAD51 GG most risk factor were in our population: [CC/GC odds ratio, 0.364 (95?% confidence interval; CI, 0.168?C0.788) p?=?0.009, CC/GG odds ratio, 0.828 (95?% CI, 0.411?C1.668) p?=?0.596], GG/GC odds ratio, 2.276 (95?% CI, 1.497?C3.460) p?=?0.001]. There was a significant association of breast cancer risk with RAD51 GG and CC polymorphism.     

Birth size and breast cancer risk: re-analysis of individual participant data from 32 studies

Background

Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size–breast cancer association.

Methods and Findings

Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02–1.09) and parental recall when the participants were children (1.02; 95% CI 0.99–1.05), but not in those based on adult self-reports, or maternal recall during the woman''s adulthood (0.98; 95% CI 0.95–1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000–3.499 kg, the risk was 0.96 (CI 0.80–1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00–1.25) in those who weighed ≥ 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03–1.10] and 1.09 [95% CI 1.03–1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution.

Conclusions

This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood.     

Time-related improvement of survival in resectable gastric cancer: the role of Japanese-style gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy

Background

Late presentation of patients at advanced stages when little or no benefit can be derived from any form of therapy is the hallmark of breast cancer in Nigerian women. Recent global cancer statistics indicate rising global incidence of breast cancer and the increase is occurring at a faster rate in populations of the developing countries that hitherto enjoyed low incidence of the disease. Worried by this prevailing situation and with recent data suggesting that health behavior may be influenced by level of awareness about breast cancer, a cross-sectional study was designed to assess the knowledge, attitude and practices of community-dwelling women in Nigeria towards breast cancer.

Methods

One thousand community-dwelling women from a semi-urban neighborhood in Nigeria were recruited for the study in January and February 2000 using interviewer-administered questionnaires designed to elicit sociodemographic information and knowledge, attitude and practices of these women towards breast cancer. Data analysis was carried out using Statistical Analysis Software (SAS) version 8.2.

Results

Study participants had poor knowledge of breast cancer. Mean knowledge score was 42.3% and only 214 participants (21.4%) knew that breast cancer presents commonly as a painless breast lump. Practice of breast self examination (BSE) was low; only 432 participants (43.2%) admitted to carrying out the procedure in the past year. Only 91 study participants (9.1%) had clinical breast examination (CBE) in the past year. Women with higher level of education (X² = 80.66, p < 0.0001) and those employed in professional jobs (X² = 47.11, p < 0.0001) were significantly more knowledgeable about breast cancer. Participants with higher level of education were 3.6 times more likely to practice BSE (Odds ratio [OR] = 3.56, 95% Confidence interval [CI] 2.58–4.92).

Conclusion

The results of this study suggest that community-dwelling women in Nigeria have poor knowledge of breast cancer and minority practice BSE and CBE. In addition, education appears to be the major determinant of level of knowledge and health behavior among the study participants. We recommend the establishment and sustenance of institutional framework and policy guidelines that will enhance adequate and urgent dissemination of information about breast cancer to all women in Nigeria.     

Ethiopian women's breast cancer self-examination practices and associated factors. A systematic review and meta-analysis

BackgroundBreast neoplasm is the most frequently diagnosed and the leading cause of cancer death in the vast majority of the countries. Breast cancer self-examination is a check-up of a woman does at home to look for changes or problems in the breast tissue. The benefit of early recognition is for early treatment that is more effective, higher long-term survival rates and better quality of life. The aim of this review was to determine the pooled prevalence of breast cancer self-examination practice and identify its associated factors among Ethiopian women.MethodsGoogle Scholar, PubMed, Science Direct, web of science, and Cochrane Library were used for search of articles. This review includes thirty four articles conducted in Ethiopia between 2011 and 2020. The review contains 14,908 women to determine the ever pooled prevalence of breast cancer self-examination practice. Health workers and students made up 28.35% of the total participants. Data were extracted using a standardized data extraction format prepared in Microsoft Excel and analyzed with Stata 14. To assess heterogeneity I² test were used. A random effect meta-analysis model was used to estimate the pooled breast cancer self-examination (BCSE) practice of Ethiopian women. Moreover associated factors were also assessed.ResultsIn Ethiopian women, the overall ever and regular pooled breast cancer self-examination practice was 36% (95% CI: 28, 43) and 16% (95% CI: 28, 43) respectively. The ever pooled prevalence for health workers or students was 53% (95% CI: 41, 65), whereas for other participants it was 25% (95% CI: 19, 30). Good knowledge about breast self-examination (AOR: 3.69: 95% CI: 2.70, 5.05), positive attitude towards BCSE (AOR: 2.72: 95% CI: 1.74, 4.24), Getting to know people with breast cancer(AOR: 2.77: 95% CI: 1.51, 5.09), family history of breast cancer (AOR: 2.49: 95% CI: 1.60, 3.88) and personal history of breast cancer (AOR: 2.26: 95% CI: 1.70, 3.01) were associated factors to BCSE practice among Ethiopian women. All of the studies included in this review were conducted in a cross-sectional design was a limitation of this review and meta-analysis.ConclusionThis review and meta-analysis showed the ever and regular pooled prevalence of BCSE among Ethiopian women. More than one third of Ethiopian women ever practiced BCSE. We recommend that awareness creation should be perform in order to tackle the risk of breast cancer.     

Breast fine-needle aspiration malondialdehyde deoxyguanosine adduct in breast cancer

Abstract

This study has analysed the generation of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adduct [M₁dG], a biomarker of oxidative stress and lipid peroxidation, in breast fine-needle aspirate samples of 22 patients with breast cancer, at different clinical stages, in respect to 13 controls. The multivariate analysis show that M₁dG adduct was higher in cases than in controls (Mean Ratio (MR) = 5.26, 95% CI = 3.16–8.77). Increased M₁dG was observed in women with a tumour grade 3 and a pathological diameter 2 (MR = 7.61, 95% CI = 3.91–14.80 and MR = 5.75, 95% CI = 3.13–10.59, respectively). A trend with increasing tumour grade and pathological diameter was present (MR = 1.98, 95% CI = 1.57–2.50 and MR = 2.44, 95% CI = 1.71–3.48, respectively). Not significant effects of age and smoking habit were found (MR = 1.58, 95% CI = 0.92–2.72 and MR = 1.68, 95% CI 0.88–3.20, respectively). An increment over the background frequency of M₁dG can contribute to breast cancer development. Increasing severity of breast tumour can influence DNA damage level.     

Randomization in the Canadian National Breast Screening Study: a review for evidence of subversion

The authors assess the randomization strategy that had been used in the Canadian National Breast Screening Study (NBSS). Document experts at a private investigation and security company were hired to assist in reviewing instances in which names of subjects were altered in the "allocation books" (the basic instrument used to assign, at random, participants to either the mammography or the usual-care arm). The review was restricted to records from 3 NBSS centres where women assigned to the mammography arm had a distinctly higher (not necessarily significant) number of deaths from breast cancer than those assigned to the usual-care arm, and to records from 2 centres where, for limited periods, administrative problems were reported. In most cases the underlying, original name could be identified. The document experts found no evidence of a deliberate attempt to conceal the alterations. A search of the NBSS database for the underlying and superimposed names revealed that only 1 of the women whose name had been deleted or superimpsed died of breast cancer. She was in the mammography arm. The authors'' thorough review of ways in which the randomization could have been subverted failed to uncover credible evidence of it. They conclude that even if there had been acts of subversion, they could only have been few in number and, given that there was only 1 death from breast cancer in the group reviewed, the alterations could have had only a trivial effect on the study findings as reported in 1992.     

Effectiveness of the public health policy for breast cancer screening in Finland: population based cohort study.

OBJECTIVE: To evaluate the effectiveness of screening for breast cancer as a public health policy. DESIGN: Follow up in 1987-92 of Finnish women invited to join the screening programme in 1987-9 and of the control women (balanced by age and matched by municipality of residence), who were not invited to the service screening. SETTING: Finland. SUBJECTS: Of the Finnish women born in 1927-39, 89893 women invited for screening and 68862 controls were followed; 1584 breast cancers were diagnosed. MAIN OUTCOME MEASURES: Rate ratio of deaths from breast cancer among the women invited for screening to deaths among those not invited. RESULTS: There were 385 deaths from breast cancer, of which 127 were among the 1584 incident cases in 1987-92. The rate ratio of death was 0.76 (95% confidence interval 0.53 to 1.09). The effect was larger and significant (0.56; 0.33 to 0.95) among women aged under 56 years at entry. 20 cancers were prevented (one death prevented per 10000 screens). CONCLUSIONS: A breast screening programme can achieve a similar effect on mortality as achieved by the trials for breast cancer screening. However, it may be difficult to justify a screening programme as a public health policy on the basis of the mortality reduction only. Whether to run a screening programme as a public health policy also depends on its effects on the quality of life of the target population and what the resources would be used for if screening was not done. Given all the different dimensions in the effect, mammography based breast screening is probably justifiable as a public health policy.     

Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers

Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio [HR] = 1.32, 95% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95% CI: 1.02-1.24, p(trend) = 0.02) but not in BRCA1 carriers. rs3803662 was associated with increased breast cancer risk in both BRCA1 and BRCA2 mutation carriers (per-allele HR = 1.13, 95% CI: 1.06-1.20, p(trend) = 5 x 10(-5) in BRCA1 and BRCA2 combined). These loci appear to interact multiplicatively on breast cancer risk in BRCA2 mutation carriers. The differences in the effects of the FGFR2 and MAP3K1 SNPs between BRCA1 and BRCA2 carriers point to differences in the biology of BRCA1 and BRCA2 breast cancer tumors and confirm the distinct nature of breast cancer in BRCA1 mutation carriers.     

Invasive Breast Cancer Incidence in 2,305,427 Screened Asymptomatic Women: Estimated Long Term Outcomes during Menopause Using a Systematic Review

Background

Earlier studies of breast cancer, screening mammography, and mortality reduction may have inflated lifetime and long-term risk estimates for invasive breast cancer due to limitations in their data collection methods and interpretation.

Objective

To estimate the percentage of asymptomatic peri/postmenopausal women who will be diagnosed with a first invasive breast cancer over their next 25 years of life.

Methods

A systematic review identified peer-reviewed published studies that: 1) enrolled no study participants with a history of invasive breast cancer; 2) specified the number of women enrolled; 3) reported the number of women diagnosed with a first invasive breast cancer; 4) did not overcount [count a woman multiple times]; and, 5) defined the length of follow-up. Data sources included PubMed, Cochrane Library, and an annotated library of 4,409 full-text menopause-related papers collected and reviewed by the first author from 1974 through 2008. Linear regression predicted incidence of first invasive breast cancer, based on follow-up duration in all studies that met the our inclusion criteria, and in a subset of these studies that included only women who were 1) at least 50 years old and 2) either at least 50 or less than 50 but surgically menopausal at enrollment.

Results

Nineteen studies met the inclusion criteria. They included a total of 2,305,427 peri/postmenopasual women. The mean cumulative incidence rate of first invasive breast cancer increased by 0.20% for each year of age (95% CI: 0.17, 0.23; p < 0.01; R² = 0.90). Over 25 years of follow-up, an estimated 94.55% of women will remain breast cancer-free (95% CI: 93.97, 95.13). In the 12 studies (n = 1,711,178) that enrolled only postmenopausal women, an estimated 0.23% of women will be diagnosed with a first invasive breast cancer each year (95% CI: 0.18, 0.28; p < 0.01, R² = 0.88).

Conclusion

The vast majority (99.75%) of screened asymptomatic peri/postmenopasual women will not be diagnosed with invasive breast cancer each year. Approximately 95% will not be diagnosed with invasive breast cancer during 25 years of follow-up. Women who receive clinical examinations, but do not have mammograms, will have higher cancer-free rates because innocuous positives (comprising 30-50% of mammography diagnoses) will remain undetected. Informed consent to asymptomatic women should include these results and consideration of the benefits of avoiding mammograms.