Breast cancer development and breast cancer progression involves the deregulation of growth factors leading to uncontrolled cellular proliferation, invasion and metastasis. Transforming growth factor (TGF)-beta plays a crucial role in breast cancer because it has the potential to act as either a tumor suppressor or a pro-oncogenic chemokine. A cross-communication between the TGF-beta signaling network and estrogens has been postulated, which is important for breast tumorigenesis. Here, we provide evidence that inhibition of TGF-beta signaling is associated with a rapid estrogen-dependent nongenomic action. Moreover, we were able to demonstrate that estrogens disrupt the TGF-beta signaling network as well as TGF-beta functions in breast cancer cells via the G protein-coupled receptor 30 (GPR30). Silencing of GPR30 in MCF-7 cells completely reduced the ability of 17-beta-estradiol (E2) to inhibit the TGF-beta pathway. Likewise, in GPR30-deficient MDA-MB-231 breast cancer cells, E2 achieved the ability to suppress TGF-beta signaling only after transfection with GPR30-encoding plasmids. It is most interesting that the antiestrogen fulvestrant (ICI 182,780), which possesses agonistic activity at the GPR30, also diminished TGF-beta signaling. Further experiments attempted to characterize the molecular mechanism by which activated GPR30 inhibits the TGF-beta pathway. Our results indicate that GPR30 induces the stimulation of the mitogen-activated protein kinases (MAPKs), which interferes with the activation of Smad proteins. Inhibition of MAPK activity prevented the ability of E2 from suppressing TGF-beta signaling. These findings are of great clinical relevance, because down-regulation of TGF-beta signaling is associated with the development of breast cancer resistance in response to antiestrogens.

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Background: The German Mammography Screening Program (German MSP) is population-based and intended for women aged 50-69 years (approximately 10.5 million). The program started in 2005 and was implemented within 5 years. This article describes the implementation, structure, and screening process, and presents the results of initial examinations for the prevalence phase. Methods: Data were collected annually from invitation centers (invitation, attendance), screening units (performance, outcomes), and cancer registries (incidence). Results: In 2009, 92% of all annually eligible women were invited; 50% of the annually eligible population participated. The total cancer detection rate in the period of 2005-2009 was 8.1/1,000; the corresponding recall rate was 5.9%. 19.6% of detected cancers were ductal carcinoma in situ; 76.7% of invasive cancers were ≤ 20 mm in size, 30.2% were ≤ 10 mm, and 75.3% were node-negative. During the implementation period, incidence increased by 37 and 56% in the old and new federal states, respectively. Incidence rates decreased following the prevalence phase. Conclusion: The German MSP was successfully implemented. The results of the prevalence phase meet the target values of the European guidelines. Proper functioning of the program is also verified by its effects on breast cancer incidence. To draw reliable conclusions regarding the long-term effects of the program, results from the routine screening rounds have to be awaited.

The CanScreen5 project is a global cancer screening data repository that aims to report the status and performance of breast, cervical and colorectal cancer screening programs using a harmonized set of criteria and indicators. Data collected mainly from the Ministry of Health in each country underwent quality validation and ultimately became publicly available through a Web-based portal. Until September 2022, 84 participating countries reported data for breast (n = 57), cervical (n = 75) or colorectal (n = 51) cancer screening programs in the repository. Substantial heterogeneity was observed regarding program organization and performance. Reported screening coverage ranged from 1.7% (Bangladesh) to 85.5% (England, United Kingdom) for breast cancer, from 2.1% (Côte d’Ivoire) to 86.3% (Sweden) for cervical cancer, and from 0.6% (Hungary) to 64.5% (the Netherlands) for colorectal cancer screening programs. Large variability was observed regarding compliance to further assessment of screening programs and detection rates reported for precancers and cancers. A concern is lack of data to estimate performance indicators across the screening continuum. This underscores the need for programs to incorporate quality assurance protocols supported by robust information systems. Program organization requires improvement in resource-limited settings, where screening is likely to be resource-stratified and tailored to country-specific situations.

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