Importance Breast cancer is a leading cause of premature mortality among U.S. women. Early detection has been shown to be associated with reduced breast cancer morbidity and mortality. This report updates the American Cancer Society (ACS) 2003 breast cancer screening guideline for women at average risk for breast cancer. Process The ACS commissioned a systematic evidence review of the breast cancer screening literature to inform the update, and a supplemental analysis of mammography registry data to address questions related to the screening interval. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. Evidence Synthesis Mammography screening in women aged 40–69 years is associated with a reduction in breast cancer deaths across a range of study designs, and inferential evidence supports breast cancer screening in women who are age 70 years and older and are in good health. Estimates of the cumulative lifetime risk of false positive exams are greater if screening begins at younger ages due to the greater number of mammograms, as well as the higher recall rate in younger women. The quality of the evidence for overdiagnosis is not sufficient to estimate a lifetime risk with confidence. Analysis examining the screening interval demonstrates more favorable tumor characteristics when premenopausal women are screened annually vs. biennially. Evidence does not support routine clinical breast examination as a screening method for average risk women. Recommendations The ACS recommends that women with an average risk of breast cancer should undergo regular screening mammography starting at age 45 years (strong recommendation). Women who are ages 45 to 54 years should be screened annually (qualified recommendation). Women who are age 55 years and older should transition to biennial screening or have the opportunity to continue screening annually (qualified recommendation). Women should have the opportunity to begin annual screening between the ages of 40 and 44 years (qualified recommendation). Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or more (qualified recommendation). The ACS does not recommend clinical breast examination for breast cancer screening among average-risk women at any age (qualified recommendation).
Tamoxifen significantly reduces tumor recurrence in certain patients with early-stage estrogen receptor-positive breast cancer, but markers predictive of treatment failure have not been identified. Here, we generated gene expression profiles of hormone receptor-positive primary breast cancers in a set of 60 patients treated with adjuvant tamoxifen monotherapy. An expression signature predictive of disease-free survival was reduced to a two-gene ratio, HOXB13 versus IL17BR, which outperformed existing biomarkers. Ectopic expression of HOXB13 in MCF10A breast epithelial cells enhances motility and invasion in vitro, and its expression is increased in both preinvasive and invasive primary breast cancer. The HOXB13:IL17BR expression ratio may be useful for identifying patients appropriate for alternative therapeutic regimens in early-stage breast cancer.
Findings from the National Cancer Institute’s National Lung Screening Trial established that lung cancer mortality in specific high-risk groups can be reduced by annual screening with low-dose computed tomography. These findings indicate that the adoption of lung cancer screening could save many lives. Based on the results of the National Lung Screening Trial, the American Cancer Society is issuing an initial guideline for lung cancer screening. This guideline recommends that clinicians with access to high-volume, high-quality lung cancer screening and treatment centers should initiate a discussion about screening with apparently healthy patients aged 55 years to 74 years who have at least a 30-pack-year smoking history and who currently smoke or have quit within the past 15 years. A process of informed and shared decision-making with a clinician related to the potential benefits, limitations, and harms associated with screening for lung cancer with low-dose computed tomography should occur before any decision is made to initiate lung cancer screening. Smoking cessation counseling remains a high priority for clinical attention in discussions with current smokers, who should be informed of their continuing risk of lung cancer. Screening should not be viewed as an alternative to smoking cessation.
It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and impaired delivery/efficacy of chemotherapeutics through reduced perfusion. Genetic and pharmacological inhibition of angiotensin-II type-1 receptor (AT1) reverses obesity-augmented desmoplasia and tumor growth and improves response to chemotherapy. Augmented activation of pancreatic stellate cells (PSCs) in obesity is induced by tumor-associated neutrophils (TANs) recruited by adipocyte-secreted IL-1β. PSCs further secrete IL-1β, and inactivation of PSCs reduces IL-1β expression and TAN recruitment. Furthermore, depletion of TANs, IL-1β inhibition, or inactivation of PSCs prevents obesity-accelerated tumor growth. In pancreatic cancer patients, we confirmed that obesity is associated with increased desmoplasia and reduced response to chemotherapy. We conclude that crosstalk between adipocytes, TANs, and PSCs exacerbates desmoplasia and promotes tumor progression in obesity.
Novel amphiphilic biodegradable graft copolymer based on poly(aspartic acid) was prepared by attaching monomethoxy polyethylene glycol (mPEG) as hydrophiphic segment to poly(aspartic acid‐g‐octadecylamine) (PASP‐g‐ODA) as hydrophobic backbone. The chemical structures of amphiphilic copolymers were confirmed by FTIR and 1H NMR spectroscopy. The polymeric micelles were prepared with solvent evaporation and their physicochemical properties in aqueous media were characterized by dynamic light scattering (DLS) and fluorescence spectroscopy. These micelles were confirmed to be pH‐sensitive by measuring optical transmittance of micelle solution and the size of micellar aggregates. The number average diameter of polymeric micelles prepared in medium at pH 2.5 was larger than that in neutral and basic medium and showed a bimodal size distribution because of the protonation of carboxyl groups in backbone. Furthermore, the polymeric micelle can load water‐insoluble drug (podophyllotoxin), and the drug release from micelles showed a pH‐dependency. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006
Nipple-sparing mastectomy may be suitable for selected cases of breast carcinoma with low probability of nipple involvement by carcinoma and prophylactic procedures. A retroareolar en-face margin may be used to test for occult involvement in patients undergoing nipple-sparing mastectomy.
BACKGROUND Tumor size has long been recognized as the strongest predictor of the outcome of patients with invasive breast carcinoma, although it has not been settled whether the correlation between tumor size and the chance of death is independent of the method of detection, nor is it clear how tumor size at the time of treatment may be translated into a specific expectation of survival. In this report, the authors provide such a method. METHODS A Kaplan–Meier survival analysis was carried out for a population of 1352 women with invasive breast carcinoma who were treated at the Van Nuys Breast Center between 1966 and 1990, and the data were analyzed together with survival data published by others. RESULTS The authors found that the survival of patients with invasive breast carcinoma was a direct function of tumor size, independent of the method of detection. The results showed that the correlation between tumor size and survival was well fit by a simple equation, with which survival predictions could be made from information on tumor size. For example, a comparison of three large populations studied over the last 5 decades revealed a marked improvement (≈ 35% absolute) in the survival of patients with invasive breast carcinoma diagnosed on clinical grounds that could be ascribed to a reduction in tumor size. However, the capacity of screening mammography to find smaller tumors remains the best way reduce breast carcinoma deaths, with the potential for adding an additional ≈ 20% absolute reduction in breast carcinoma deaths. The mathematic correlation between tumor size and survival is consistent with a biologic mechanism in which lethal distant metastasis occurs by discrete events of spread such that, for every invasive breast carcinoma cell in the primary tumor at the time of surgery, there is approximately a 1‐in‐1‐billion chance that a lethal distant metastasis has formed. CONCLUSIONS The correlation between tumor size and lethality is well captured by a simple equation that is consistent with breast carcinoma death as the result of discrete events of cellular spread occurring with small but definable probabilities. Cancer 2002;95:713–23. © 2002 American Cancer Society. DOI 10.1002/cncr.10742
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