Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

The investigation of electromagnetic precursors to earthquakes in Armenia

The present work provides a sufficient theoretical substantiation of the anomalous distribution for Very-Low-Frequency (VLF) radio waves which is observed for all radio routes controlled by the National Survey for Seismic Protection (NSSP) of the Republic of Armenia. This event is connected with the ionosphere excitement over the strong seismic event preparation zone under the influence of intensively oscillated VLF electromagnetic waves falling on the ionosphere from the source called an area of uniformly oriented Zones of Separated Charges (ZSC) in the strong seismic preparation zone. ZSC, formed at the interfaces of solid, liquid, and gaseous phases of rocks, acquire identical orientation under the action of increasing elastic strain forces. These strain forces may cause the effect of mutual polarisation of ZSC in the field of their high concentration. As a result, in the strong earthquake preparation zone, the most sensitive to the deformation ZSC, non-linear electromagnetic effects may be observed. One of these effects is the irreversibility of non-stationary electromagnetic processes (INP). It is shown that the INP method developed by Balassanian and Kabilsky (Balassanian, 1990) may prove to be very sensitive to the deformations of geological medium in the earthquake preparation zone.JCR Journalope

The investigation of electromagnetic precursors to earthquakes in Armenia

The present work provides a sufficient theoretical substantiation of the anomalous distribution for Very-Low-Frequency (VLF) radio waves which is observed for all radio routes controlled by the National Survey for Seismic Protection (NSSP) of the Republic of Armenia. This event is connected with the ionosphere excitement over the strong seismic event preparation zone under the influence of intensively oscillated VLF electromagnetic waves falling on the ionosphere from the source called an area of uniformly oriented Zones of Separated Charges (ZSC) in the strong seismic preparation zone. ZSC, formed at the interfaces of solid, liquid, and gaseous phases of rocks, acquire identical orientation under the action of increasing elastic strain forces. These strain forces may cause the effect of mutual polarisation of ZSC in the field of their high concentration. As a result, in the strong earthquake preparation zone, the most sensitive to the deformation ZSC, non-linear electromagnetic effects may be observed. One of these effects is the irreversibility of non-stationary electromagnetic processes (INP). It is shown that the INP method developed by Balassanian and Kabilsky (Balassanian, 1990) may prove to be very sensitive to the deformations of geological medium in the earthquake preparation zone