G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells.

DCE-MRI assessment of response to neoadjuvant SABR in early stage breast cancer: Comparisons of single versus three fraction schemes and two different imaging time delays post-SABR.

Purpose: To determine the effect of dose fractionation and time delay post-neoadjuvant stereotactic ablative radiotherapy (SABR) on dynamic contrast-enhanced (DCE)-MRI parameters in early stage breast cancer patients.

Materials And Methods: DCE-MRI was acquired in 17 patients pre- and post-SABR. Five patients were imaged 6-7 days post-21 Gy/1fraction (group 1), six 16-19 days post-21 Gy/1fraction (group 2), and six 16-18 days post-30 Gy/3 fractions every other day (group 3).

An alternative to standard lumpectomy: a 5-year case series review of oncoplastic breast surgery outcomes in a Canadian setting.

Background: Oncoplastic surgery (OPS) is becoming the new standard of care for breast-conserving surgery (BCS). It has become increasingly popular in Europe; however, it has not yet been widely accepted in North America. This study aims to describe the experience with OPS at a Canadian tertiary care centre.

KISS1/KISS1R and Breast Cancer: Metastasis Promoter.

Kisspeptins (KPs), peptide products of the kisspeptin-1 () gene, are the endogenous ligands for the KISS1 receptor, KISS1R, which is a G protein-coupled receptor. In many human tumors, functions as a metastasis-suppressor gene and KISS1/KISS1R signaling has antimetastatic and tumor-suppressor roles. On the contrary, emerging evidence indicates that the KP/KISS1R pathway plays detrimental roles in triple negative breast cancer (TNBC), the most difficult type of breast cancer to treat.

Recurrence and mortality after breast-conserving surgery without radiation.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer; studies have demonstrated that adjuvant rt confers a protective effect with respect to recurrence, although no randomized trials have shown a survival benefit.

Methods: This retrospective cohort study used Ontario data linked through ices to examine patients treated for breast cancer between 1 April 2007 and 31 March 2014. The primary outcome was death or recurrence.

Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial.

Programmed cell death protein 1 (PD-1) blockade is only effective in a minority of patients, prompting the search for combinatorial therapies that increase responses. Identifying effective combinations requires lengthy testing and so far has shown few successes. To accelerate progress Voorwerk and colleagues (Nat Med.

Trends in immediate breast reconstruction and radiation after mastectomy: A population study.

In the last decade, there has been an increase in women undergoing immediate breast reconstruction (IBR) at the time of mastectomy. Recent literature suggests a shift in practice: Surgeons are becoming more comfortable with IBR in the setting of possible postoperative adjuvant radiotherapy, despite the known complications. This study sought to investigate, at a population level, the patient and surgeon characteristics associated with the use of IBR and which of these factors were predictive of adjuvant radiotherapy.

Mastectomy flap necrosis after nipple-sparing mastectomy and immediate implant-based reconstruction: An evaluation of tumescence and sharp dissection technique on surgical outcomes.

Nipple-sparing mastectomy (NSM) with immediate implant-based reconstruction has better esthetic outcomes and improved patient satisfaction, in addition to being oncologically safe. A known complication of NSM is skin flap necrosis. The use of tumescence and sharp dissection may decrease this complication compared to the standard NSM technique using electrocautery.

The Standardization of Outpatient Procedure (STOP) Narcotics: A Prospective Health Systems Intervention to Reduce Opioid Use in Ambulatory Breast Surgery.

Background: During the past 15 years, opioid-related overdose death rates for women have increased 471%. Many surgeons provide opioid prescriptions well in excess of what patients actually use. This study assessed a health systems intervention to control pain adequately while reducing opioid prescriptions in ambulatory breast surgery.

Position statement on defining and standardizing an oncoplastic approach to breast-conserving surgery in Canada.

Although mastectomy is an effective procedure, it can have a negative effect on body image, sense of attractiveness, and sexuality. As opposed to the combination of breast oncologic surgery and plastic surgery, whose primary focus is on replacing lost volume, breast-conserving oncoplastic surgery (ops) redistributes remaining breast tissue in a manner that requires vision, anatomic knowledge, and an appreciation of esthetics, symmetry, and breast function. Modern surgical treatment of breast cancer can be realized only with breast and plastic surgeons working together using oncoplastic techniques to deliver superior cosmetic and cancer outcomes alike.

Stereotactic image-guided neoadjuvant ablative single-dose radiation, then lumpectomy, for early breast cancer: the SIGNAL prospective single-arm trial of single-dose radiation therapy.

Background And Purpose: Adjuvant whole-breast irradiation after breast-conserving surgery, typically delivered over several weeks, is the traditional standard of care for low-risk breast cancer. More recently, hypofractionated, partial-breast irradiation has increasingly become established. Neoadjuvant single-fraction radiotherapy (rt) is an uncommon approach wherein the unresected lesion is irradiated preoperatively in a single fraction.

Cost-effectiveness analysis of multigene expression profiling assays to guide adjuvant therapy decisions in women with invasive early-stage breast cancer.

Gene expression profiling (GEP) testing using 12-gene recurrence score (RS) assay (EndoPredict®), 58-gene RS assay (Prosigna®), and 21-gene RS assay (Oncotype DX®) is available to aid in chemotherapy decision-making when traditional clinicopathological predictors are insufficient to accurately determine recurrence risk in women with axillary lymph node-negative, hormone receptor-positive, and human epidermal growth factor-receptor 2-negative early-stage breast cancer. We examined the cost-effectiveness of incorporating these assays into standard practice. A decision model was built to project lifetime clinical and economic consequences of different adjuvant treatment-guiding strategies.

Intraoperative photoacoustic screening of breast cancer: a new perspective on malignancy visualization and surgical guidance.

High re-excision rates in breast-conserving surgery call for a new intraoperative approach to the lumpectomy margin evaluation problem. The unique intraoperative imaging system, presented here, demonstrated the capability of photoacoustic tomography (PAT) to deliver optical sensitivity and specificity, along with over 2-cm imaging depth, in a clinical setting. The system enabled the evaluation of tumor extent, shape, morphology, and position within lumpectomy specimens measuring up to 11 cm in diameter.

Reducing the dose of gadolinium-based contrast agents for DCE-MRI guided SBRT: The effects on inter and intra observer variability for preoperative target volume delineation in early stage breast cancer patients.

Background And Purpose: This study aimed to determine the effects of reducing the dose of contrast agent (CA) in a DCE-MRI scan on inter- and intra-observer variability in the context of MRI-guided target volume delineation for stereotactic body radiation therapy of early stage breast cancer patients. This is in hopes of reducing risks to patients due to findings of residual CA in brain and bone.

Materials And Methods: Twenty-three patients receiving neoadjuvant radiation therapy were enrolled.

TBX3 promotes progression of pre-invasive breast cancer cells by inducing EMT and directly up-regulating SLUG.

The acquisition of cellular invasiveness by breast epithelial cells and subsequent transition from ductal carcinoma in situ (DCIS) to invasive breast cancer is a critical step in breast cancer progression. Little is known about the molecular dynamics governing this transition. We have previously shown that overexpression of the transcriptional regulator TBX3 in DCIS-like cells increases survival, growth, and invasiveness.

MNK1/NODAL Signaling Promotes Invasive Progression of Breast Ductal Carcinoma .

The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion.

Appropriate treatment receipt after breast-conserving surgery.

Background: Breast-conserving surgery (bcs) and radiation therapy (rt) are the standard of care for early breast cancer, although some women receive ipsilateral mastectomy or adjuvant tamoxifen, both of which can be appropriate alternatives to rt. Objectives of the present study were to determine the proportion of women who are treated appropriately after bcs and to identify factors associated with non-receipt of rt.

Methods: This retrospective cohort study used Ontario data linked at the Institute for Clinical and Evaluative Sciences to examine 33,718 patients who received bcs during 2004-2010.

A prospective intervention to improve happiness and reduce burnout in oncologists.

Background: There is a paucity of data about effective interventions to improve happiness and reduce burnout in oncologists. Benjamin Franklin developed a 13-week program of "necessary activities" or "virtues" (temperance, silence, order, resolution, frugality, industry, sincerity, justice, moderation, cleanliness, tranquility, chastity, and humility) to follow, in his attempt at self-improvement. In this pilot study, we explored whether using a modified version of this was associated with any discernable impact on physician happiness, burnout, or compliance with each of the virtues.

Negative Pressure Wound Therapy Use to Decrease Surgical Nosocomial Events in Colorectal Resections (NEPTUNE): A Randomized Controlled Trial.

Objective: Determine if negative pressure wound therapy (NPWT) reduces surgical site infection (SSI) in primarily closed incision after open and laparoscopic-converted colorectal surgery.

Background: SSIs after colorectal surgery are a common cause of morbidity. The prophylactic effect of NPWT has not been established.

Survival outcome differences based on treatments used and knowledge of the primary tumour site for patients with cancer of unknown and known primary in Ontario.

Introduction: Patients with cancer of unknown primary (cup) have pathologically confirmed metastatic tumours with unidentifiable primary tumours. Currently, very little is known about the relationship between the treatment of patients with cup and their survival outcomes. Thus, we compared oncologic treatment and survival outcomes for patients in Ontario with cup against those for a cohort of patients with metastatic cancer of known primary site.

Clinical utility of radioactive seed localization in nonpalpable breast cancer: A retrospective single institutional cohort study.

Background: With advances in mammographic screening techniques, it has become easier to detect nonpalpable breast lesions at an early stage. Pre-surgical localization of lesions by radioactive seed localization (RSL) has several benefits over conventional wire localization (WL) in guiding breast conserving surgery. In this study, we compared WL and RSL, focusing on the relationship between the techniques and in-breast recurrence or margin positivity.

KISS1/KISS1R in Cancer: Friend or Foe?

The gene encodes KISS1, a protein that is rapidly processed in serum into smaller but biologically active peptides called kisspeptins (KPs). KISS1 and the KPs signal via the G-protein coupled receptor KISS1R. While KISS1 and KPs are recognized as potent positive regulators of the reproductive neuroendocrine axis in mammals, the first reported role for KISS1 was that of metastasis suppression in melanoma.

The matrix protein Fibulin-3 promotes KISS1R induced triple negative breast cancer cell invasion.

Breast cancer is a leading cause of cancer mortality. In particular, triple negative breast cancer (TNBC) comprise a heterogeneous group of basal-like tumors lacking estrogen receptor (ERα), progesterone receptor (PR) and HER2 (ErbB2). TNBC represents 15-20% of all breast cancers and occurs frequently in women under 50 years of age.

Characterisation of the Carboxypeptidase G2 Catalytic Site and Design of New Inhibitors for Cancer Therapy.

The enzyme carboxypeptidase G2 (CPG2) is used in antibody-directed enzyme prodrug therapy (ADEPT) to catalyse the formation of an active drug from an inert prodrug. Free CPG2 in the bloodstream must be inhibited before administration of the prodrug in order to avoid a systemic reaction in the patient. Although a few small-molecule CPG2 inhibitors have been reported, none has been taken forward thus far.