Rethinking Screening for Breast Cancer and Prostate Cancer
Department of Surgery and Radiology, University of California, San Francisco, San Francisco, CA 94115, USA.JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 10/2009; 302(15):1685-92. DOI: 10.1001/jama.2009.1498
After 20 years of screening for breast and prostate cancer, several observations can be made. First, the incidence of these cancers increased after the introduction of screening but has never returned to prescreening levels. Second, the increase in the relative fraction of early stage cancers has increased. Third, the incidence of regional cancers has not decreased at a commensurate rate. One possible explanation is that screening may be increasing the burden of low-risk cancers without significantly reducing the burden of more aggressively growing cancers and therefore not resulting in the anticipated reduction in cancer mortality. To reduce morbidity and mortality from prostate cancer and breast cancer, new approaches for screening, early detection, and prevention for both diseases should be considered.
Full-text previewDOI: · Available from: esculape.com
[Show abstract] [Hide abstract]
- "Women were also asked how they felt about the DCIS term itself as well as other alternative terms for DCIS that have been proposed (see Table 3). These terms included ductal intraepithelial neoplasia (DIN) introduced in 1988 by Tavassoli , indolent lesions of epithelial origin (IDLE) advocated for by Esserman and colleagues  and a plain language description of abnormal cells currently used in the LORIS trial (abnormal cells in the milk duct of the breast that had not spread into other breast tissue) . When told the DCIS terminology, women appeared overwhelmed by the language and typically only recognised the term carcinoma. "
ABSTRACT: Objective: There are increasing rates of mastectomy and bi-lateral mastectomy in women diagnosed with ductal carcinoma in situ (DCIS). To help women avoid decisions that lead to unnecessary aggressive treatments, there have been recent calls to remove the cancer terminology from descriptions of DCIS. We investigated how different proposed terminologies for DCIS affect women's perceived concern and management preferences. Materials and methods: Qualitative study using semi-structured interviews with a community sample of 26 Australian women varying by education and cancer screening experience. Women responded to a hypothetical scenario using terminology with and without the cancer term to describe DCIS. Results: Among a sample of women with no experience of a DCIS diagnosis, a hypothetical scenario involving a diagnosis of DCIS elicited high concern regardless of the terminology used to describe it. Women generally exhibited stronger negative reactions when a cancer term was used to describe DCIS compared to a non-cancer term, and most preferred the diagnosis be given as a description of abnormal cells. Overall women expressed interest in watchful waiting for DCIS but displayed preferences for very frequent monitoring with this management approach. Conclusion: Communicating a diagnosis of DCIS using terminology that does not include the cancer term was preferred by many women and may enable discussions about more conservative management options. However, women's preference for frequent monitoring during watchful waiting suggests women need more education and reassurance about this management approach.
[Show abstract] [Hide abstract]
- "The effectiveness of breast cancer screening is extensively debated, particularly regarding the estimated proportion of overdiagnosed cancers [3, 22]. Identification of these overdiagnosed screen-detected cancers is challenging. "
ABSTRACT: Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007-2011, who participated in the national screening program (biennial screening ages 50-75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p < 0.0001; 95 % CI 1.73-3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM.
[Show abstract] [Hide abstract]
- "Although both mammography and MRI demonstrate excellent sensitivity for detecting tissue abnormalities, they lack sufficient specificity to unequivocally distinguish malignant tissue from benign tissue (Esserman et al., 2009). The question remains as to whether premalignant molecular markers can be used noninvasively to detect aggressive cancers. "
ABSTRACT: Inhibitors of heat-shock protein 90 (Hsp90) have demonstrated an unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained, but could be influenced by ectopically expressed Hsp90 in tumors. In this work, we synthesized Hsp90 inhibitors that can carry optical or radioiodinated probes via a polyethyleneglycol tether. We show that these tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and become internalized. The internalization process is blocked by Hsp90 antibodies, suggesting that active cycling of the protein occurs at the plasma membrane. In mice, we observed exquisite accumulation of the fluor-tethered versions within breast tumors at very sensitive levels. Cell-based assays with the radiolabeled version showed picomolar detection in cells that express ectopic Hsp90. Our findings show that fluor-tethered or radiolabeled inhibitors that target ectopic Hsp90 can be used to detect breast cancer malignancies through noninvasive imaging.