[show abstract][hide abstract] ABSTRACT: Mutations in the p53 tumor suppressor gene and accumulation of its protein in breast tissue are thought to play a role in breast carcinogenesis. However, few studies have prospectively investigated the association of p53 immunopositivity and/or p53 alterations in women with benign breast disease in relation to the subsequent risk of invasive breast cancer. We carried out a case-control study nested within a large cohort of women biopsied for benign breast disease in order to address this question. After exclusions, 491 breast cancer cases and 471 controls were available for analysis. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Neither p53 immunopositivity nor genetic alterations in p53 (either missense mutations or polymorphisms) was associated with altered risk of subsequent breast cancer. However, the combination of both p53 immunopositivity and any p53 nucleotide change was associated with an approximate 5-fold nonsignificant increase in risk (adjusted OR 4.79, 95% CI 0.28-82.31) but the confidence intervals were extremely wide. Our findings raise the possibility that the combination of p53 protein accumulation and the presence of genetic alterations may identify a group at increased risk of breast cancer.
[show abstract][hide abstract] ABSTRACT: Women with a history of benign breast disease are at increased risk of subsequent breast cancer. However, few studies have examined whether established breast cancer risk factors other than histology are associated with an altered risk of breast cancer in women with benign breast disease. We used a nested case-control design within a large, multi-center cohort of women biopsied for benign breast disease (BBD) to estimate odds ratios for breast cancer in association with exposure to a range of personal and lifestyle factors.
Cases were women biopsied for BBD who subsequently developed breast cancer; controls were individually matched to cases on center and age at diagnosis and were women biopsied for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After excluding women with prevalent breast cancer, 1357 records (661 case records and 696 records) were available for analysis. We used conditional logistic regression to obtain crude and multivariable-adjusted estimates of the association between specific factors and risk of breast cancer.
In multivariable analyses age at first live birth, number of pregnancies, and postmenopausal status were inversely associated with risk of breast cancer. The odds ratio for women with age at first birth <25 years and >or=3 pregnancies, relative to nulliparous women, was 0.49, 95% confidence interval 0.13-0.79, and that for postmenopausal women relative to premenopausal women was 0.60, 95% CI 0.37-0.99.
Further study of personal factors influencing the risk of breast cancer in women with BBD may help to identify subgroups of the population at increased risk of invasive disease.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: We used a nested case-control design within a large, multi-center cohort of women who underwent a biopsy for benign breast disease (BBD) to assess the association of broad histologic groupings and specific histologic entities with risk of breast cancer. METHODS: Cases were all women who had a biopsy for BBD and who subsequently developed breast cancer; controls were individually matched to cases and were women with a biopsy for BBD who did not develop breast cancer in the same follow-up interval as that for the cases. After exclusions, 1,239 records (615 cases and 624 controls) were available for analysis. We used conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs). RESULTS: Relative to non-proliferative BBD/normal pathology, the multivariable-adjusted odds ratio for proliferative lesions without atypia was 1.45 (95% CI 1.10-1.90), and that for atypical hyperplasia was 5.27 (95% CI 2.29-12.15). The presence of multiple foci of columnar cell hyperplasia and of complex fibroadenoma without atypia was associated with a non-significantly increased risk of breast cancer, whereas sclerosing adenosis, radial scar, and papilloma showed no association with risk. CONCLUSION: Our results indicate that, compared to women with normal pathology/non-proliferative disease, women with proliferative disease without atypia have a modestly increased risk of breast cancer, whereas women with atypical hyperplasia have a substantially increased risk.
Cancer Causes and Control 01/2010; · 3.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous studies that have assessed breast cancer in relation to zinc, selenium, calcium, and iron have yielded inconsistent results but have not measured breast tissue levels. In a case-control study involving 252 matched pairs nested in a cohort of 9,315 women with benign breast disease, we investigated these associations by directly measuring elemental levels in breast tissue using X-ray fluorescence spectroscopy. Quintile analyses revealed positive associations of breast cancer, of borderline statistical significance, with zinc [highest versus lowest quintile: odds ratio (OR), 1.37; 95% confidence limit (95% CL), 0.91, 2.05; P(trend) = 0.04], iron (highest versus lowest quintile: OR, 1.58; 95% CL, 1.02, 2.44; P(trend) = 0.07), and calcium (highest versus lowest quintile: OR, 1.46; 95% CL, 0.98, 2.17; P(trend) = 0.14), but little association with selenium (highest versus lowest quintile: OR, 1.10; 95% CL, 0.72, 1.68; P(trend) = 0.76). The associations were weakened by mutual adjustment. Furthermore, after stratification by menopausal status, the positive association between iron and breast cancer was confined to postmenopausal women (highest versus lowest quintile: OR, 2.77; 95% CL, 1.25, 6.13; P(trend) = 0.008), whereas the associations for zinc, calcium, and selenium did not differ by menopausal stratum. In conclusion, our data raise the possibility that relatively high levels of zinc, iron, and calcium in benign breast tissue may be associated with a modest increase in risk of subsequent breast cancer.