Chimeras- Greek Mythology or Scientific Reality? Identification of Actionable Chimeric RNAs for Personalized Prevention of Breast Cancer

https://openworks.mdanderson.org/sumexp23/1080/thumbnail.jp

Association between Clinical Characteristics and Pathologic Nodal Stage in Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2-Negative (HER2-) Breast Cancer

https://openworks.mdanderson.org/sumexp21/1228/thumbnail.jp

Utility of gross tumor palpability or tumor size as a measure of drug efficacy for cancer prevention

View full abstracthttps://openworks.mdanderson.org/leading-edge/1050/thumbnail.jp

Long-term avasimibe treatment abolishes the breast cancer preventative efficacy of statin in a spontaneous mouse model of breast cancer

View full abstracthttps://openworks.mdanderson.org/leading-edge/1023/thumbnail.jp

Survival Outcomes After Omission of Surgery for Ductal Carcinoma In Situ

Clinical trials of active surveillance (AS) for Ductal Carcinoma in Situ (DCIS) are underway. We sought to understand the historical management of biologically favorable DCIS and to determine the outcomes of patients who did not have immediate surgery. Using data from the NCDB from 2004 to 2017, the selected cohort included women \u3e40 years of age, with low or intermediate grade and hormone receptor (HR) positive DCIS. AS was defined as either no surgery or surgery \u3e12 months from diagnosis. Women in the AS group were compared to women who had immediate surgery. A Cochran-Armitage test was used to assess the trend of AS over year of diagnosis. Kaplan-Meier curves were estimated to compare overall survival (OS), stratified by age (\u3c50, 50-64, ≥65), and Cox proportional hazard models were used to determine the effects of prognostic factors on survival distributions. 74,367 women met study inclusion criteria; 2384 (3.2%) were treated with AS. The proportion of patients in the AS cohort increased yearly, peaking in 2017 at 4.2% (p \u3c 0.01). On multivariable analysis, increasing age (OR 1.02, p \u3c 0.01), black race (OR 1.7, p \u3c 0.001), and being uninsured (OR 2.2, p \u3c 0.001) were associated with increased likelihood of AS. In women \u3c50 years of age, OS outcomes were similar, with 10-year OS of 97.4% in the immediate surgery cohort versus 99.1% in AS cohort (p = 0.43). The proportion of patients with DCIS treated with AS has remained small but is increasing over time. AS of biologically favorable DCIS in younger, healthier women is not associated with adverse survival

Effectiveness Without Efficacy: Cautionary Tale from a Landmark Breast Cancer Randomized Controlled Trial

Background: “Old” randomized controlled trials established breast conserving therapy (BCT) and total mastectomy (TM) equivalence for treating early breast cancer, whereas recent literature report improved survival with BCT. To reconcile this, we performed a simulation study and re-analyzed B-06 trial data. Methods: We estimated the distributions for overall survival (OS), cumulative incidence functions for breast-cancer-specific death (BCSD) and other causes-specific death (OCSD) by BCT and TM. The restricted mean survival time (RMST) difference and hazard ratio between the two arms were estimated. Given the estimated distributions, we simulated cause-specific death times from each arm, evaluating the power to test treatment difference in OS, BCSD, and OCSD with different sample sizes, follow-up times, and a modified setting by simulating BCT-arm OCSD times from the distribution of patients not receiving radiation. Results: With 200 months follow-up, the average BCT-over-TM gain measured by RMST was 3.7 months for OS and 4.5 months for BCSD. Increasing the trial size to 5,000 per arm, there is a 79.2% chance to detect the OS benefit with RMST and 92.4% for BCSD. A nonproportional increase of OCSD in BCT compared to TM was observed after 144 months, and particularly after 200 months post treatments. When OCSD times of BCT were simulated using patients not receiving radiation, the estimated OS gain increased to 4.4 months, and the power increased to 92.2%. Conclusions: The late excess other-cause-death, likely due to radiation, in the BCT arm and sample size constraints limited the power to report BCT superiority. Given radiation delivered in the era of B-06 trial, BCT and TM remain largely equivalent

DCIS and axillary nodal evaluation: compliance with national guidelines

BACKGROUND: The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) provide guidelines regarding axillary nodal evaluation in ductal carcinoma in situ (DCIS), but data regarding national compliance with these guidelines remains incomplete. METHODS: We conducted a retrospective review of the National Cancer Data Base (NCDB) analyzing all surgical approaches to axillary evaluation in patients with DCIS. Logistic regression analysis was used to assess the multivariate relationship between patient demographics, clinical characteristics, and probability of axillary evaluation. RESULTS: We identified 88,083 patients diagnosed with DCIS between 1998 and 2011; 31,912 (37%) underwent total mastectomy (TM) and 55,349 (63%) had breast conserving therapy (BCT). Axillary evaluation increased from 44.4% in 1998 to 63.3% in 2011. In TM patients, axillary evaluation increased from 74.3% in 1998 to 93.4% in 2011. This correlated with an increase in sentinel lymph node biopsy (SLNB) from 24.3 to 77.1%, while ALND decreased from 50.0 to 16.3% (p <0.01). In BCT patients, evaluation increased from 20.1 to 43.9%; SLNB increased from 7.2 to 39.4% and ALND decreased from 12.9 to 4.5%. Factors associated with axillary nodal evaluation in BCT patients included practice type and facility location. Among TM patients, use of axillary lymph node dissection (ALND) for axillary staging was associated with earlier year of diagnosis, black race, and older age, as well as community practice setting and practice location in the Southern US. CONCLUSIONS: Compliance with national guidelines regarding axillary evaluation in DCIS remains varied. Practice type and location-based differences suggest opportunities for education regarding the appropriate use of axillary nodal evaluation in patients with DCIS

Radiomic and deep learning characterization of breast parenchyma on full field digital mammograms and specimen radiographs: A pilot study of a potential cancer field effect

Purpose: In women with biopsy-proven breast cancer, histologically normal areas of the parenchyma have shown molecular similarity to the tumor, supporting a potential cancer field effect. The purpose of this work was to investigate relationships of human-engineered radiomic and deep learning features between regions across the breast in mammographic parenchymal patterns and specimen radiographs. Approach: This study included mammograms from 74 patients with at least 1 identified malignant tumor, of whom 32 also possessed intraoperative radiographs of mastectomy specimens. Mammograms were acquired with a Hologic system and specimen radiographs were acquired with a Fujifilm imaging system. All images were retrospectively collected under an Institutional Review Board-approved protocol. Regions of interest (ROI) of 128 × 128 pixels were selected from three regions: within the identified tumor, near to the tumor, and far from the tumor. Radiographic texture analysis was used to extract 45 radiomic features and transfer learning was used to extract 20 deep learning features in each region. Kendall’s Tau-b and Pearson correlation tests were performed to assess relationships between features in each region. Results: Statistically significant correlations in select subgroups of features with tumor, near to the tumor, and far from the tumor ROI regions were identified in both mammograms and specimen radiographs. Intensity-based features were found to show significant correlations with ROI regions across both modalities. Conclusions: Results support our hypothesis of a potential cancer field effect, accessible radiographically, across tumor and non-tumor regions, thus indicating the potential for computerized analysis of mammographic parenchymal patterns to predict breast cancer risk.</p

Evaluation of sensitivity to endocrine herapy index (SET2,3) for response to neoadjuvant endocrine therapy and longer-term breast cancer patient outcomes (Alliance Z1031)

PURPOSE: To evaluate prediction of response and event-free survival (EFS) following neoadjuvant endocrine therapy by SET2,3 index of nonproliferation gene expression related to estrogen and progesterone receptors adjusted for baseline prognosis. EXPERIMENTAL DESIGN: A correlative study was conducted of SET2,3 measured from gene expression profiles of diagnostic tumor (Agilent microarrays) in 379 women with cStage II-III breast cancer from the American College of Surgeons Oncology Group Z1031 neoadjuvant aromatase inhibitor trial SET2,3 was dichotomized using the previously published cutoff. Fisher exact test was used to assess the association between SET2,3 and low proliferation at week 2-4 [Ki67 ≤ 10% or complete cell-cycle arrest (CCCA; Ki67 ≤ 2.7%)] and PEPI-0 rate in cohort B, and the association between SET2,3 and ypStage 0/I in all patients. Cox models were used to assess EFS with respect to SET2,3 excluding cohort B patients who switched to chemotherapy. RESULTS: Patients with high SET2,3 had higher rate of pharmacodynamic response than patients with low SET2,3 (Ki67 ≤ 10% in 88.2% vs. 56.9%, P \u3c 0.0001; CCCA in 50.0% vs. 26.2%, P = 0.0054), but rate of ypStage 0/I (24.0% vs. 20.4%, P = 0.4580) or PEPI = 0 (28.4% vs. 20.6%, P = 0.3419) was not different. Patients with high SET2,3 had longer EFS than patients with low SET2,3 (HR, 0.52, 95% confidence interval: 0.34-0.80; P = 0.0026). CONCLUSIONS: This exploratory analysis of Z1031 data demonstrated a higher rate of pharmacodynamic suppression of proliferation and longer EFS in high SET2,3 disease relative to low SET2,3 disease. The ypStage 0/I rate and PEPI = 0 rate were similar with respect to SET2,3

Prospective Study of Pain Outcomes Associated With Breast Surgery in Women With Nonhereditary Breast Cancer

OBJECTIVE: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes. SUMMARY OF BACKGROUND DATA: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery. METHODS: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and QOL and decision satisfaction. RESULTS: Of 288 women (mean age 56 years, 58% non-Hispanic White), 50 had CPM, 75 had unilateral mastectomy, and 163 had BCS. Mean pain severity scores were higher at one (2.78 vs 1.9, P = 0.016) and 6 months (2.79 vs 1.96, P = 0.031) postsurgery in women who had CPM versus those who did not, but there was no difference at 12 and 18 months. Comparing mastectomy versus BCS, pain severity was higher at 1 and 12 months. There was a significant interaction between pain severity and time point for CPM ( P = 0.006), but not mastectomy status ( P = 0.069). Regardless of surgery type, Black women had higher pain severity ( P = 0.004) than White women. Higher pain interference was associated with lower QOL ( P \u3c 0.001) and lower decision satisfaction ( P = 0.034). CONCLUSIONS: Providers should counsel women considering mastectomy about the potential for greater acute pain and its impact on overall well-being. Racial/ethnic disparities in pain exist and influence pain management in breast surgical patients