Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs were developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.

Previous studies linked disadvantaged neighborhoods to poor cancer outcomes. The Neighborhood Deprivation Index (NDI) quantifies socioeconomic disadvantage, but its impact on gastroesophageal adenocarcinoma outcomes remains understudied. We conducted a retrospective analysis of 40,589 patients with esophageal or gastric adenocarcinoma from the SEER database (1996–2015), stratifying them by NDI: less disadvantaged (NDI < 60) and highly disadvantaged (NDI ≥ 60). Multivariate regression showed NDI ≥ 60 was independently associated with worse overall survival (OS) (HR 1.027, p = 0.017) and disease-specific survival (DSS) (HR 1.025, p = 0.04). Other predictors of poor OS and DSS included older age (≥60 years old), male sex, single marital status, lack of insurance, advanced stage/grade, and gastric tumor site. In contrast, Hispanic and non-Hispanic Black ethnicity, urban residence, and undergoing surgery were associated with better outcomes. Disadvantaged neighborhoods are linked to poorer survival in upper GI cancers, likely due to socioeconomic barriers. Addressing social determinants of health is crucial to reducing these disparities.

Mixed -phenotype acute leukemia (MPAL) is a rare form of leukemia with ambiguous lineage, and there are challenges in accurately diagnosing this entity according to formal criteria. Here we report a case which was initially diagnosed as "AML " based on atypical peripheral blood flow cytometry that was subsequently determined to be B -ALL with KMT2A rearrangement based on marrow results. Although KMT2A rearrangements represent a defining genetic abnormality for acute leukemia of ambiguous lineage, this case did not meet the criteria for MPAL based on WHO 2022 criteria. This case highlights the diagnostic challenges of MPAL and the potential limitations of the current classification. We discuss the most appropriate workup and management of these patients and identify areas for future study.

The role of immune checkpoint inhibitors (ICIs) for patients with gastroesophageal (GE) cancer with liver metastasis remains unclear. Our objective was to investigate if ICIs are beneficial in patients with GE cancer with liver metastasis. We searched PubMed, Embase, ESMO, and ASCO Meeting Abstracts for phase III randomized clinical trials (RCTs) testing ICIs in metastatic/advanced GE cancer from 2017 to 2023. Seven studies were included. OS was similar among all patients (HR 0.72 [0.67,0.77], p < .001), in patients without (HR 0.73 [0.67,0.81], p < .001, I2 = 0.0%), and with liver metastasis (HR 0.74 [0.67,0.81], p < .001, I2 = 0.0%). PFS was also similar among all patients (HR 0.63 [0.57,0.70], p < .001), without (HR 0.62 [0.51,0.76], p < .001), and with liver metastasis (HR 0.66 [0.57,0.76], p < .001). ICIs showed no difference in benefit in patients with GE cancer regardless of liver metastasis. Future studies could focus on deciphering the tumor microenvironment of liver metastasis as an area of translational research.

Previous studies linked disadvantaged neighborhoods to poor cancer outcomes. The Neighborhood Deprivation Index (NDI) quantifies socioeconomic disadvantage but its impact on gastroesophageal adenocarcinoma outcomes remains understudied. We conducted a retrospective analysis of 40,589 patients with esophageal or gastric adenocarcinoma from the SEER database (1996–2015), stratifying them by NDI: less disadvantaged (NDI < 60) and highly disadvantaged (NDI ≥60). Multivariate regression showed NDI ≥60 was independently associated with worse overall survival (OS) (HR 1.027, p=0.017) and disease-specific survival (DSS) (HR 1.025, p=0.04). Other predictors of poor OS and DSS included older age (≥ 60 years old), male sex, single marital status, lack of insurance, advanced stage/grade, and gastric tumor site. In contrast, Hispanic and non-Hispanic Black ethnicity, urban residence, and undergoing surgery were associated with better outcomes. Disadvantaged neighborhoods are linked to poorer survival in upper GI cancers, likely due to socioeconomic barriers. Addressing social determinants of health is crucial to reducing these disparities.