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PurposeTo quantify the risk of second primary breast cancer in the contralateral breast (CB) after radiotherapy (RT) for first breast cancer.Methods and materialsThe study population included participants in the Women's Environmental, Cancer, and Radiation Epidemiology study: 708 cases (women with asynchronous bilateral breast cancer) and 1399 controls (women with unilateral breast cancer) counter-matched on radiation treatment. Participants were 1.0 Gy of absorbed dose to the specific quadrant of the CB had a 2.5-fold greater risk for CB cancer than unexposed women (RR = 2.5, 95% CI 1.4-4.5). No excess risk was observed in women >40 years of age. Women 5 years had a RR of 3.0 (95% CI 1.1-8.1), and the dose response was significant (excess RR per Gy of 1.0, 95% CI 0.1-3.0).ConclusionsWomen 1.0 Gy to the CB had an elevated, long-term risk of developing a second primary CB cancer. The risk is inversely related to age at exposure and is dose dependent.

U.S. forests, particularly in the eastern states, provide an important offset to greenhouse gas (GHG) emissions. Some have proposed that forest‐based natural climate solutions can be strengthened via a number of strategies, including increases in the production of forest biomass energy. We used output from a forest dynamics model (SORTIE‐ND) in combination with a GHG accounting tool (ForGATE) to estimate the carbon consequences of current and intensified timber harvest regimes in the Northeastern United States. We considered a range of carbon pools including forest ecosystem pools, forest product pools, and waste pools, along with different scenarios of feedstock production for biomass energy. The business‐as‐usual (BAU) scenario, which represents current harvest practices derived from the analysis of U.S. Forest Service Forest Inventory and Analysis data, sequestered more net CO2 equivalents than any of the intensified harvest and feedstock utilization scenarios over the next decade, the most important time period for combatting climate change. Increasing the intensity of timber harvest increased total emissions and reduced landscape average forest carbon stocks, resulting in reduced net carbon sequestration relative to current harvest regimes. Net carbon sequestration "parity points," where the regional cumulative net carbon sequestration from alternate intensified harvest scenarios converge with and then exceed the BAU baseline, ranged from 12 to 40 years. A "no harvest" scenario provides an estimate of an upper bound on forest carbon sequestration in the region given the expected successional dynamics of the region's forests but ignores leakage. Regional net carbon sequestration is primarily influenced by (1) the harvest regime and amount of forest biomass removal, (2) the degree to which bioenergy displaces fossil fuel use, and (3) the proportion of biomass diverted to energy feedstocks versus wood products. [ABSTRACT FROM AUTHOR]

Context.--Lymph node status and the number of lymph node (LN) positive for cancer cells are the most important prognostic factors in breast cancer. Extranodal tumor extension (ENTE) has been used as a histopathologic feature to classify patients into high risk versus low risk for local recurrence. However, in the current era of early detection and systemic therapy, the prognostic significance of ENTE is not as well defined in patients with 1 to 3 LNs positive for cancer. Objective.--To determine whether the amount of tumor burden in an axillary dissection or the presence of ENTE provides any additional information regarding patient outcome in patents with 1 to 3 positive LN results. Design.--Clinical and pathologic factors were identified for 456 patients with breast cancer at the University of Texas MD Anderson Cancer Center, Houston, who had pT1 tumors and 1 to 3 LNs positive for cancer and were treated by mastectomy, with or without postmastectomy radiotherapy, between 1978 and 2007. Results.--Of the 456 patients, 257 (56.4%), 141 (31.6%), and 58 (12.7%) patients had 1, 2, or 3 positive LN results, respectively. Extranodal tumor extension was present in 99 patients (21.7%) and was absent in the remaining 357 cases (78.3%). Seventy-six patients (16.7%) received radiation therapy. Patients had both worse overall survival time and disease-free survival when ENTE was present, regardless of the amount, as long as the treatment era was not included in the multivariate analysis (pre-2000 versus post-2000). However, ENTE was no longer significant on multivariate analysis when the year of treatment was taken into account. Conclusions.--The number of positive LNs remains an important predictor of survival in patients with 1 to 3 positive LN results, but the prognostic significance of ENTE in this cohort of patients has diminished over time. (Arch Pathol Lab Med. 2015; 139:1288-1294; doi: 10.5858/arpa.2014-0375-0A), Lymph node (LN) status and the number of LNs positive for cancer cells are the most important prognostic factors in patients with breast cancer. Postoperative chest wall and regional LN [...]

Abstract Background Radiation is a standard component of treatment for patients with locoregional recurrence (LRR) of breast cancer following mastectomy. The current study reports the results of a 10% radiation dose escalation in these patients. Methods 159 patients treated at MD Anderson Cancer Center between 1994-2006 with isolated LRR after mastectomy alone were reviewed. Patients in the standard treatment group (65 pts, 40.9%) were treated to 50 Gy comprehensively plus a boost of 10 Gy. The dose escalated group (94 pts, 59.1%) was treated to 54 Gy comprehensively and a minimum 12 Gy boost. Median dose in the standard dose and dose escalated group was 60 Gy (±1 Gy, 95% CI) and 66 Gy (±0.5 Gy, 95% CI) respectively. Median follow up for living patients was 94 months from time of recurrence. Results The actuarial five year locoregional control (LRC) rate was 77% for the entire study population. The five year overall survival and disease-free survival was 55% and 41%, respectively. On multivariate analysis, initial tumor size (p = 0.03), time to initial LRR (p = 0.03), absence of gross tumor at the time of radiation (p = 0.001) and Her2 status (p = 0.03) were associated with improved LRC. Five year LRC rates were similar in patients with a complete response to chemotherapy without surgery and patients with a complete surgical excision (77% vs 83%, p = NS), compared to a 63% LRC rate in patients with gross disease at the time of radiation (p = 0.024). LRC rates were 80% in the standard dose group and 75% in the dose escalated group (p = NS). Conclusions While LRR following mastectomy is potentially curable, distant metastasis and local control rates remain suboptimal. Radiation dose escalation did not appear to improve LRC. Given significant local failure rates, these patients are good candidates for additional strategies to improve their outcomes.

Abstract Background Since the first suggestion of prospectively identifiable cancer stem cells in solid tumors, efforts have been made to characterize reported cancer stem cell surrogates in existing cancer cell lines, and cell lines rich with these surrogates have been used to screen for cancer stem cell targeted agents. Although 293T cells were derived from human embryonic kidney, transplantation of these cells into the mammary fat pad yields aggressive tumors that self-renew as evidenced by serial xenograft passages through transplantation. Herein we fully characterize cancer stem cell-like features in 293T human embryonic kidney cells. Results 293T cells can be readily cultured and passaged as spheres in serum-free stem cell promoting culture conditions. Cells cultured in vitro as three-dimensional spheres (3D) were shown to contain higher ALDH1 and CD44+/CD24- population compared to monolayer cells. These cells were also resistant to radiation and upregulate stem cell survival signaling including β-catenin, Notch1 and Survivin in response to radiation. Moreover, 3D spheres generated from the 293T cells have increased expression of mesenchymal genes including vimentin, n-cadherin, zeb1, snail and slug as well as pro-metastatic genes RhoC, Tenascin C and MTA1. In addition, microRNAs implicated in self-renewal and metastases were markedly reduced in 3D spheres. Conclusions 293T cells exhibit a cancer stem cell-like phenotype when cultured as 3D spheres and represent an important research tool for studying the molecular and biological mechanisms of cancer stem cells and for testing and developing novel targets for cancer therapy.