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

Change in Biomarker Profile After Neoadjuvant Chemotherapy is Prognostic and Common Among Patients with HER2+ Breast Cancer.

BACKGROUND: Rates of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer have improved, especially among human epidermal growth factor 2-positive (HER2+) and triple-negative subtypes. The frequency and significance of biomarker profile change in residual disease are unclear. This study aimed to determine the rate of biomarker profile changes after NAC and the impact on clinical outcomes in a contemporary cohort. METHODS: Upon institutional review board approval, the study identified 634 consecutive patients treated with NAC between 2010 and 2022 at two academic institutions. The study cohort was focused on patients with residual disease who underwent biomarker profile retesting. Biomarker profile change for each subtype was compared across groups using Fisher-Irwin tests. Cox Proportional Hazards Model and Kaplan-Meier plots were performed to evaluate the association of changed versus unchanged biomarker profile with event-free survival. RESULTS: Biomarker retesting was performed for 259 (61.4 %) of 422 patients with residual disease. Biomarker profile change occurred in 18.1 % overall and was significantly higher among those with pre-NAC HER2+ disease (32.7 %, 17/52) than among those with HER2-disease (14.5 %, 30/207) (p = 0.004). Conversion of pre-NAC biomarker profiles of HR+HER2- and HR+HER2+ to triple-negative breast cancer (TNBC) post-NAC may be associated with worse event-free survival, hazard ratios of 2.23 (95 % confidence interval [CI], 0.90-5.53; p = 0.08), trending toward significance, and 36.7 (95 % CI, 2.2-610.8; p = 0.01), respectively. CONCLUSIONS: The results from one of the largest contemporary cohorts demonstrated that biomarker profile change in patients with residual disease after NAC was common. Furthermore, specific biomarker profile change in residual disease may have prognostic value. These findings strengthen the rationale for routine re-testing of biomarkers in residual disease after NAC

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 in-tra-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 ¼ .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] ¼ 1.98, 95% confidence interval [CI] ¼ 1.31 to 3.00; luminal A subtype tumors: HR ¼ 2.43, 95% CI ¼ 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

PLANNING-SOCIAL LEADERSHIP: A CONCEPTUAL STUDY ON LE CORBUSIER

Abstract not availabl

PLANNING-SOCIAL LEADERSHIP: A CONCEPTUAL STUDY ON LE CORBUSIER

Abstract not availabl