Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.

Purpose: In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy.

Methods: In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS).

Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.

Purpose: While MEK inhibitors demonstrated activity in metastatic triple negative breast cancer (mTNBC) preclinical studies, preclinical, and clinical studies implicate rapid development of resistance limiting clinical benefit. The purpose of this study was to determine response rate for Trametinib alone and in combination with Uprosertib in patients with mTNBC previously treated with chemotherapy.

Methods: This was an open-label, two-part, phase II, single-arm, multicenter study.

Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.

Proinflammatory Dietary Pattern and Risk of Total and Subtypes of Breast Cancer Among U.S. Women.

Background: Dietary patterns promoting chronic inflammation, including the empirical dietary inflammatory pattern (EDIP), have been associated with certain cancers. Investigating whether this dietary pattern is associated with breast cancer-where the role of inflammation is less well-defined-could provide valuable insights and potentially improve strategies for preventing this cancer.

Methods: We prospectively followed 76,386 women from Nurses' Health Study (NHS, 1984-2018) and 92,886 women from Nurses' Health Study II (NHSII, 1991-2019).

The role of heparan sulfate in enhancing the chemotherapeutic response in triple-negative breast cancer.

Background: Breast cancer, one of the most common forms of cancer, is associated with the highest cancer-related mortality among women worldwide. In comparison to other types of breast cancer, patients diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst outcome because current therapies do not produce long-lasting responses. Hence, innovative therapies that produce persisting responses are a critical need.

The RAL Small G Proteins Are Clinically Relevant Targets in Triple Negative Breast Cancer.

Breast cancer (BC) is the most frequent cancer and second-leading cause of cancer deaths in women in the United States. While RAS mutations are infrequent in BC, triple-negative (TN) and HER2-positive (HER2+) BC both exhibit increased RAS activity. Here, we tested the RAS effectors RALA and RALB, which are overexpressed in BC, as tractable molecular targets in these subtypes.

A video intervention to improve patient understanding of tumor genomic testing in patients with cancer.

Introduction: Tumor genomic testing (TGT) is standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is frequently omitted. The purpose of this study was to evaluate the impact of a concise 4 min video for patient education prior to TGT.

Case report: Characterization of the immunologic and molecular landscape in a unique presentation of invasive lobular carcinoma with concurrent uterine carcinosarcoma treated with immunotherapy.

Invasive lobular breast cancer (ILC) is characterized by a relatively high risk for late recurrence and a unique metastatic pattern with an increased risk for metastasis to gynecologic organs and peritoneum. We present a unique case of recurrent ILC with metastasis to the abdominal peritoneum as well as the uterine myometrium and cervix. Treatment was complicated by the discovery of concomitant uterine carcinosarcoma.

The survival benefit of adjuvant trastuzumab with or without chemotherapy in the management of small (T1mic, T1a, T1b, T1c), node negative HER2+ breast cancer.

There is limited data regarding the added benefit of adjuvant systemic therapy in the management of small, node-negative, HER2+ breast cancer. In a multi-institutional retrospective analysis using the American Society of Clinical Oncology CancerLinQ database, we compared survival outcomes among T1a-c N0 HER2+ patients diagnosed between 2010 to 2021 who received locoregional therapy alone or in combination with adjuvant trastuzumab (+/- chemotherapy). Primary outcomes were invasive disease-free survival (iDFS) and overall survival (OS).

Real-world treatment patterns of adjuvant endocrine therapy and ovarian suppression in premenopausal HR+/HER2+ breast cancer.

Background: The optimal adjuvant endocrine therapy (ET) in hormone receptor positive (HR+) and human epidermal growth factor receptor 2 positive (HER2+) premenopausal breast cancer (BC) remains unclear. Moreover, the benefit and clinical indications of ovarian suppression (OS) is poorly elucidated. We described real-world patterns surrounding choice of ET and clinicopathologic features which predicted treatment with OS in a contemporary cohort of premenopausal women with HR+/HER2+ BC.

Identifying and Treating Those at Risk: Disparities in Rapid Relapse Among TNBC Patients in the National Cancer Database.

Purpose: This study was designed to characterize features of rapid relapse TNBC (rrTNBC), an aggressive, poor prognosis breast cancer subset using the National Cancer Database (NCDB).

Methods: Patients diagnosed with TNBC between 2010 and 2019 within NCDB were included in analyses. rrTNBC was defined as all-cause mortality ≤24 months from diagnosis.

FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.

Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing.

Assay Validation of Cell-Free DNA Shallow Whole-Genome Sequencing to Determine Tumor Fraction in Advanced Cancers.

Blood-based liquid biopsy is increasingly used in clinical care of patients with cancer, and fraction of tumor-derived DNA in circulation (tumor fraction; TFx) has demonstrated clinical validity across multiple cancer types. To determine TFx, shallow whole-genome sequencing of cell-free DNA (cfDNA) can be performed from a single blood sample, using an established computational pipeline (ichorCNA), without prior knowledge of tumor mutations, in a highly cost-effective manner. We describe assay validation of this approach to facilitate broad clinical application, including evaluation of assay sensitivity, precision, repeatability, reproducibility, pre-analytic factors, and DNA quality/quantity.

A Video Intervention to Improve Patient Understanding of Tumor Genomic Testing in Patients with Cancer.

Background: Tumor genomic testing (TGT) has become standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is variable or frequently omitted. The purpose of this study was to evaluate the impact of a concise (3-4 minute) video for patient education prior to TGT.

Racial Disparities in Breast Cancer: from Detection to Treatment.

Purpose Of Review: Update on current racial disparities in the detection and treatment of breast cancer.

Recent Findings: Breast cancer remains the leading cause of cancer death among Black and Hispanic women. Mammography rates among Black and Hispanic women have surpassed those among White women, with studies now advocating for earlier initiation of breast cancer screening in Black women.

Low Hospital Volume Is Associated with Higher All-Cause Mortality in Black Women with Triple Negative Breast Cancer.

Introduction: This study examines the association between hospital volume and all-cause mortality in Black women with triple negative breast cancer (TNBC) who received surgery and chemotherapy.

Methods: Black women ages 18+ with stage I-III TNBC who received both surgery and chemotherapy were identified in the National Cancer Database (NCDB). Hospital volume was determined using the number of annual breast cancer cases divided by the number of years the hospital participated in the NCDB.

Retrospective cohort study of CDK4/6-inhibitor-induced alopecia in breast cancer patients.

Purpose: Dermatologic adverse events commonly result in the interruption of oncologic treatment, and targeted therapies are the most frequently interrupted class of anticancer agents. Alopecia is a common cutaneous adverse event reported with CK4/6i therapy. Though the clinical characteristics and therapeutic response of EIA have been well documented, few studies have characterized alopecia in patients treated with CDK4/6i.