Benign ovarian cysts and breast cancer risk.

Article Summary: Benign ovarian cysts have been suggested to influence breast cancer risk. To provide a comprehensive picture of the relation between ovarian cysts and breast cancer, we analyzed the data of 3 case-control studies conducted in northern Italy and the Swiss Canton of Vaud between 1983 and 2001. These studies included 6,315 incident, histologically confirmed breast cancer cases and 6,038 hospital-based controls. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models, including terms for sociodemographic, menstrual and reproductive factors. Overall, 4.9% of breast cancer cases and 6.6% of controls reported a history of ovarian cysts, with a multivariate OR of 0.72 (95% CI 0.62-0.85). The inverse association between ovarian cysts and breast cancer was consistent in separate strata of age at menarche, parity, age at menopause status and family history of breast cancer. No meaningful differences were also found across strata of menstrual cycle length, oral contraceptive use, history of oophorectomy and body mass index. Thus, the inverse relation between ovarian cysts and breast cancer risk was not accounted for by earlier menopause, or by any difference in reproductive and menstrual characteristics. Although some hormonal correlates of ovarian cysts may have a role on breast cancer risk, a biological explanation of this inverse association is still unclear.

Authors of Article: Bosetti C, Scotti L, Negri E, Talamini R, Levi F, Franceschi S, Montella M, Giacosa A, Vecchia CL. Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy.

Article Source: Internation Journal of Cancer, 27 Apr 2006. PMID: 16646075

Body weight and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status among Swedish women: A prospective cohort study.

Article Summary: Although obesity is one of the established risk factors for postmenopausal breast cancer, it is not clear whether this positive association differs across estrogen receptor and progesterone receptor status of breast tumors. We evaluated the association between body weight and estrogen receptor/progesterone receptor defined breast cancer risk stratified by postmenopausal hormone (PMH) use and a family history of breast cancer in the population-based Swedish Mammography Screening Cohort comprising 51,823 postmenopausal women. Relative body weight was measured by body mass index (kg/m(2)) based on self-reported weight and height collected in 1987 and 1997. Relative risks were estimated by hazard ratios derived from Cox proportional hazards regression models. During an average of 8.3-year follow-up, 1,188 invasive breast cancer cases with known estrogen receptor and progesterone receptor status were diagnosed. When comparing to normal weight group, we observed a positive association between obesity and risk for the development of estrogen receptor+ progesterone receptor+ tumors (relative risk = 1.67, 95% CI = 1.34-2.07) and an inverse association for the development of all progesterone receptor-tumors (relative risk = 0.68, 95% CI = 0.47-0.98). Statistically significant heterogeneity was observed in the relative risks between estrogen receptor+ progesterone receptor+ tumors and all progesterone receptor- tumors (p(heterogeneity) < 0.0001). The positive association of obesity with the development of estrogen receptor+ progesterone receptor+ tumors was confined to never-users of postmenouposal hormone (relative risk = 1.90 (CI 95%:1.38-2.61)) and to those without a family history of breast cancer (relative risk = 1.82 (CI 95%:1.45-2.29)). Our results support the hypothesis that excess endogenous estrogen due to obesity contributes to an increased risk of estrogen receptor+ progesterone receptor+ postmenopausal breast cancer.

Article Authors: Suzuki R, Rylander-Rudqvist T, Ye W, Saji S, Wolk A. Division of Nutritional Epidemiology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Article Source: Internation Journal of Cancer, 27 Apr 2006. PMID: 16646051

Breast cancer proteomics by laser capture microdissection, sample pooling, 54-cm IPG IEF, and differential iodine radioisotope detection.

Article Summary:The presence of progesterone receptor in estrogen receptor -positive breast cancer is associated with a good prognosis, and indicates that tumors are likely to respond to tamoxifen. However, estrogen receptor(+)/progesterone receptor(-) tumors respond less well. To reveal the potential molecular mechanism of this phenomenon, we sought to identify differential protein abundances between invasive ductal carcinoma cells from cryopreserved estrogen receptor(+)/progesterone receptor(+) and estrogen receptor(+)/progesterone receptor(-) mammary tumor specimens. Because current proteomics methods are hampered in the examination of most primary human tumor samples by the extreme tissue heterogeneity, we used laser capture microdissection to isolate tumor cells and developed a sample pooling strategy to analyze small sample protein lysates. Proteins from laser capture microdissection-harvested tumors were pooled into four sub-pools from each condition of three tumors/sub-pool, and proteins from respective paired sub-pools were co-electrophoresed by 2-DE using 54-cm IEF over pH 4-9. Abundance ratios were accurately quantified by a differential multiplex radioactive ProteoTope method at low attomole levels ( approximately 3.6 μg protein per labeling reaction, less than 180 ng per multiplex protein sample per 54-cm gel). Applying this approach, differentially displayed proteins were identified by MS using comigrating non-radioactively labeled tumor proteins. They include decreased cytochrome b(5) and transgelin, and more abundant CRABP-II, cyclophilin A, Neudesin, and hemoglobin in estrogen receptor(+)/progesterone receptor(+) tumors versus estrogen receptor(+)/progesterone receptor(-)providing a possible explanation for differential susceptibility against tamoxifen as a result of deregulated cytochrome b(5)-dependent metabolism. This study demonstrates the potential of ProteoTope and laser capture microdissection to enable extremely sensitive and precise differential analyses from well-defined primary clinical specimen.

Article Authors: Neubauer H, Clare SE, Kurek R, Fehm T, Wallwiener D, Sotlar K, Nordheim A, Wozny W, Schwall GP, Poznanovic S, Sastri C, Hunzinger C, Stegmann W, Schrattenholz A, Cahill MA. University Women's Hospital, Tubingen, Germany.

Article Source: Electrophoresis. 2006 Apr 27;27(9):1840-1852. PMID: 16645950.

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