Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.

In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression.

Oral Selective Estrogen Receptor Degraders (SERDs) in Breast Cancer: Advances, Challenges, and Current Status.

Several endocrine therapies are currently available for the treatment of estrogen receptor (ER) positive breast cancer, but the clinical benefit of these agents is limited by endocrine therapy drug resistance. A common mechanism of endocrine therapy resistance is mutations. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has activity against mutant tumors but requires intramuscular injection and has poor bioavailability that precludes optimal drug dosing.

Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review.

Endocrine therapy forms the backbone of systemic therapy for the majority of persons with early and late-stage breast cancer. However, the side effects can negatively affect quality of life, and impact treatment adherence and overall oncological outcomes. Adverse effects on cognition are common, underreported and challenging to manage.

A single-cell and spatially resolved atlas of human breast cancers.

Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers.

Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis.

Background: High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs.

Molecular Biomarkers for Contemporary Therapies in Hormone Receptor-Positive Breast Cancer.

Systemic treatment of hormone receptor-positive (HR+) breast cancer is undergoing a renaissance, with a number of targeted therapies including CDK4/6, mTOR, and PI3K inhibitors now approved for use in combination with endocrine therapies. The increased use of targeted therapies has changed the natural history of HR+ breast cancers, with the emergence of new escape mechanisms leading to the inevitable progression of disease in patients with advanced cancers. The identification of new predictive and pharmacodynamic biomarkers to current standard-of-care therapies and discovery of new therapies is an evolving and urgent clinical challenge in this setting.

Stromal cell diversity associated with immune evasion in human triple-negative breast cancer.

The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development of stromal-targeted therapies. Single-cell RNA sequencing of five TNBCs revealed two cancer-associated fibroblast (CAF) and two perivascular-like (PVL) subpopulations.

MDM2 inhibition in combination with endocrine therapy and CDK4/6 inhibition for the treatment of ER-positive breast cancer.

Background: Resistance to endocrine therapy is a major clinical challenge in the management of oestrogen receptor (ER)-positive breast cancer. In this setting, p53 is frequently wildtype and its activity may be suppressed via upregulation of its key regulator MDM2. This underlies our rationale to evaluate MDM2 inhibition as a therapeutic strategy in treatment-resistant ER-positive breast cancer.

Window of opportunity treatment in breast cancer.

Window of opportunity therapies, which involve short-term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone-receptor positive breast cancer, a 2-week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision-making regarding treatment options. Changes in short-term biomarker endpoints such as cell proliferation measured by Ki-67 can act as surrogate markers of long-term outcomes.

The International Academy of Cytology Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy Cytopathology.

The International Academy of Cytology (IAC) gathered together a group of cytopathologists expert in breast cytology who, working with clinicians expert in breast diagnostics and management, have developed the IAC Yokohama System for Reporting Breast Fine-Needle Aspiration Biopsy (FNAB) Cytology. The project was initiated with the first cytopathology group meeting in Yokohama at the 2016 International Congress of Cytology. This IAC Yokohama System defines five categories for reporting breast cytology, each with a clear descriptive term for the category, a definition, a risk of malignancy (ROM) and a suggested management algorithm.

Efficacy of harmonic focus scalpel in seroma prevention after axillary clearance.

Introduction: Seroma formation in breast cancer patients who have undergone axillary lymph node dissection (ALND) is a source of significant discomfort and morbidity. We aimed to ascertain seroma incidence after ALND, when Harmonic Focus (HF) scalpel is used for dissection instead of conventional diathermy (CD).

Methods(and Patients): This retrospective study was carried out in a single hospital over 6 years.

Experience in dermomyofascial pouch coverage of immediate implants following skin sparing reduction mastectomy.

Background: Mastectomy for breast cancer treatment and prophylaxis has improved survival for patients. The advantage of implant reconstruction post mastectomy is that it avoids an additional donor site with its associated morbidity, which post-mastectomy autologous reconstruction necessitates. However, the deficiency of muscle coverage at the lower pole of the implant meant it relied on only skin envelope coverage, and thus has the established complication of implant exposure or infection should the skin break down.

Retinoid signaling in pancreatic cancer, injury and regeneration.

Background: Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC.

Can breast MRI predict axillary lymph node metastasis in women undergoing neoadjuvant chemotherapy.

Background: Axillary lymph node status provides important staging information. We sought to evaluate the predictive value of breast magnetic resonance imaging (MRI) in detecting axillary lymph node metastases prior to initiation of neoadjuvant chemotherapy (NAC) and in detecting residual lymph node metastases after NAC in women found to be node positive prior to NAC.

Methods: Women underwent breast MRI with axillary evaluation prior to initiation of NAC and again after completion of NAC.

Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status.

The phospholipid transfer protein STARD10 cooperates with c-erbB signaling and is overexpressed in Neu/ErbB2 breast cancers. We investigated if STARD10 expression provides additional prognostic information to HER2/neu status in primary breast cancer. A published gene expression dataset was used to determine relationships between STARD10 and HER2 mRNA levels and patient outcome.

Androgen receptor inhibits estrogen receptor-alpha activity and is prognostic in breast cancer.

There is emerging evidence that the balance between estrogen receptor-alpha (ER(alpha)) and androgen receptor (AR) signaling is a critical determinant of growth in the normal and malignant breast. In this study, we assessed AR status in a cohort of 215 invasive ductal breast carcinomas. AR and (ER(alpha)) were coexpressed in the majority (80-90%) of breast tumor cells.

Messina: a novel analysis tool to identify biologically relevant molecules in disease.

Background: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes.

Expression of S100A2 calcium-binding protein predicts response to pancreatectomy for pancreatic cancer.

Background & Aims: Current methods of preoperative staging and predicting outcome following pancreatectomy for pancreatic cancer (PC) are inadequate. We evaluated the utility of multiple biomarkers from distinct biologic pathways as potential predictive markers of response to pancreatectomy and patient survival.

Methods: We assessed the relationship of candidate biomarkers known, or suspected, to be aberrantly expressed in PC, with disease-specific survival and response to therapy in a cohort of 601 patients.

Common activation of canonical Wnt signaling in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is an extremely aggressive malignancy, which carries a dismal prognosis. Activating mutations of the Kras gene are common to the vast majority of human PDA. In addition, recent studies have demonstrated that embryonic signaling pathway such as Hedgehog and Notch are inappropriately upregulated in this disease.

Does MRI predict pathologic tumor response in women with breast cancer undergoing preoperative chemotherapy?

Background: Neoadjuvant chemotherapy precludes the accurate pre-surgical pathologic measurement of tumor size. The purpose of this study is to review imaging studies performed in patients who received preoperative chemotherapy prior to surgery and determine whether MRI, ultrasound (US) or physical exam best predicted final pathologic tumor size.

Methods: Stage I, II, and III breast cancer patients were treated with neoadjuvant therapy on trial.

Measurement of cardiac output with a non-invasive continuous wave Doppler device versus the pulmonary artery catheter: a comparative study.

Introduction And Aim: Cardiac index remains an important measured variable used to optimise fluid and haemodynamic support in the postoperative cardiac setting. Recent developments in non-invasive continuous wave Doppler devices enable rapid assessment of cardiac index with decreased morbidity. This study aimed to determine the clinical utility of one such device, the USCOM device (USCOM Ltd, Sydney, NSW), in assessing cardiac index compared with invasive continuous measurements of cardiac index using a pulmonary artery (PA) catheter.

Cyclin E expression and outcome in pancreatic ductal adenocarcinoma.

The association of high cyclin E expression with poor outcome in some cancers, in particular breast cancer, suggests that it may play an important role in tumor biology. Because the influence of cyclin E expression on outcome is yet to be examined in pancreatic cancer, we assessed the relationship between the expression of cyclin E, p27(Kip1), and survival in a large cohort of pancreatic cancer patients with long-term follow-up. Expression of cyclin E and p27(Kip1) was assessed by immunohistochemistry using tissue microarrays of tumor samples from 118 patients with pancreatic ductal adenocarcinoma (75 resections and 43 biopsies).

Overexpression of LMO4 induces mammary hyperplasia, promotes cell invasion, and is a predictor of poor outcome in breast cancer.

The zinc finger protein LMO4 is overexpressed in a high proportion of breast carcinomas. Here, we report that overexpression of a mouse mammary tumor virus (MMTV)-Lmo4 transgene in the mouse mammary gland elicits hyperplasia and mammary intraepithelial neoplasia or adenosquamous carcinoma in two transgenic strains with a tumor latency of 13-18 months. To investigate cellular processes controlled by LMO4 and those that may be deregulated during oncogenesis, we used RNA interference.