Epidermal Receptor 2-negative Breast Cancer Research Articles

Abstract P6-03-14: Conditional reprogrammed cells enable us to examine the drug resistance for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer

Abstract Objectives: Various new drugs have been developed for treating recurrent hormone receptor-positive/human epidermal receptor 2-negative breast cancer. However, directly identifying effective drugs remains difficult. In this study, we elucidated the clinical relevance of cultured cells derived from patients with recurrent hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer. Methods: We generated conditional reprogrammed cells from primary and metastatic breast cancer. CR cells were co-cultured with irradiated mouse fibroblast feeder cells in the presence of the Rho kinase inhibitor Y-27632. We performed microarray analysis using a SurePrint G3 Human GE microarray kit Ver. 2.0, and DNA target sequence using QIAseq Targeted DNA Panels to analyze the genetic variants of the 93 most commonly mutated genes in human breast cancer samples. We examined the pathological features by xenograft model. For drug screening assay, we used Cambridge Cancer Compound Library. Results: The results of microarray analysis, DNA target sequencing and xenograft experiments indicated that the mutation status and pathological features were preserved in CR cells, whereas RNA expression was different from that in the primary tumor cells, especially with respect to cell adhesion-associated pathways. The results of drug sensitivity assays involving the use of primary breast cancer CR cells were consistent with the result of Oncotype Dx. We performed drug screening assays using liver metastases, which were sensitive to 66 drugs. The result reflected the actual clinical course of this patient, resistant to taxanes and sensitive to fulvestrant plus palbociclib. Conclusion: These results supported the use of CR cells obtained from the metastatic lesions of patients with HR+/HER2− breast cancer for predicting the clinical drug efficacy. Citation Format: Rei Mimoto, Satomi Yogosawa, Atsushi Fushimi, Hiroko Nogi, Tadashi Asakura, Kiyotsugu Yoshida, Hiroshi Takeyama. Conditional reprogrammed cells enable us to examine the drug resistance for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-03-14.

Clinical implications of drug-screening assay for recurrent metastatic hormone receptor-positive, human epidermal receptor 2-negative breast cancer using conditionally reprogrammed cells

Various new drugs have been developed for treating recurrent hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2−) breast cancer. However, directly identifying effective drugs remains difficult. In this study, we elucidated the clinical relevance of cultured cells derived from patients with recurrent HR+/HER2− metastatic breast cancer. The recently established conditionally reprogrammed (CR) cell system enables us to examine heterogeneity, drug sensitivity and cell function using patient-derived tumour samples. The results of microarray analysis, DNA target sequencing and xenograft experiments indicated that the mutation status and pathological features were preserved in CR cells, whereas RNA expression was different from that in the primary tumour cells, especially with respect to cell adhesion-associated pathways. The results of drug sensitivity assays involving the use of primary breast cancer CR cells were consistent with gene expression profiling test data. We performed drug-screening assays using liver metastases, which were sensitive to 66 drugs. Importantly, the result reflected the actual clinical course of this patient. These results supported the use of CR cells obtained from the metastatic lesions of patients with HR+/HER2− breast cancer for predicting the clinical drug efficacy.

Optimal timing of delivery for women with breast cancer, according to cancer stage and hormone status: a decision-analytic model

Objective: To compare strategies for the timing of delivery in women with breast cancer and known cancer stage or hormone receptor subtype, and to determine the optimal gestational age for induction in regards to maternal-fetal outcomes. Study design: A decision-analytic model was designed comparing eight different strategies for scheduled delivery at 30, 31, 32, 33, 34, 35, 36, and 37 weeks gestation. Optimal breast cancer treatment was assumed to be delayed until after delivery. Baseline estimates of the stage- and subtype-specific mortality and the impact of delayed cancer treatment on 5-year survival rates were obtained from the literature. Outcomes factored into the model included the risk of intrauterine fetal demise, spontaneous delivery, respiratory distress syndrome, cerebral palsy, and neonatal demise at each gestational age. Univariate sensitivity analyses and Monte Carlo simulations were performed to test the robustness of our model. Results: For women with stage I–II breast cancer, delivery at 36 weeks yielded the highest number of overall quality-adjusted life years (QALYs), while maternal QALYs were maximized with delivery at 34 weeks. For stage III and IV disease, maternal QALYs were maximized at 31 and 30 weeks, respectively. For women with estrogen or progesterone receptor-positive, human epidermal receptor-2 negative breast cancer, both maternal QALYs and overall QALYs were maximized with delivery at 36 weeks. More aggressive biological phenotypes were similarly associated with optimal delivery at decreasing gestational age. Our model was heavily driven by the baseline probability of maternal death within 5 years, in addition to the expected progression of disease and decreases in survival rates with each week of non-treatment, and remained robust across reasonable ranges for all variables of interest. Conclusions: For women with breast cancer diagnosed during pregnancy, decisions regarding timing of delivery should take into consideration both cancer stage and hormone receptor subtype.