Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment.

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment.

Circulating tumour mutation detection in triple-negative breast cancer as an adjunct to tissue response assessment.

Circulating tumour DNA (ctDNA) detection via liquid biopsy is an emerging alternative to tissue biopsy, but its potential in treatment response monitoring and prognosis in triple negative breast cancer (TNBC) is not yet well understood. Here we determined the prevalence of actionable mutations detectable in ctDNA using a clinically validated cancer gene panel assay in patients with TNBC, without recurrence at the time of study entry. Sequencing of plasma DNA and validation of variants from 130 TNBC patients collected within 7 months of primary treatment completion revealed that 7.

Implementation of pharmacogenetic testing in oncology: -guided dosing to prevent fluoropyrimidine toxicity in British Columbia.

Fluoropyrimidine toxicity is often due to variations in the gene () encoding dihydropyrimidine dehydrogenase (DPD). genotyping can be used to adjust doses to reduce the likelihood of fluoropyrimidine toxicity while maintaining therapeutically effective drug levels. A multiplex QPCR assay was locally developed to allow genotyping for six variants.

Breast-Conserving Therapy is Associated with Improved Survival Without an Increased Risk of Locoregional Recurrence Compared with Mastectomy in Both Clinically Node-Positive and Node-Negative Breast Cancer Patients.

Introduction: Randomized trials demonstrated equivalent survival between breast-conserving surgery combined with radiotherapy (BCT) and mastectomy alone. Contemporary retrospective studies using pathological stage have reported improved survival with BCT. However, pathological information is unknown before surgery.

Does age affect outcome with breast cancer?

Prior data about the influence of age at diagnosis of breast cancer on patient outcomes and survival has been conflicting. Using the Breast Cancer Outcomes Unit database at BC Cancer, this retrospective population-based study identified a cohort of 24,469 patients diagnosed with invasive breast cancer between 2005 and 2014. Median follow-up was 11.

Breast conserving surgery combined with radiation therapy offers improved survival over mastectomy in early-stage breast cancer.

Introduction: Landmark trials established equivalent survival regardless of extent of breast surgery in early-stage breast cancer. However, recent studies suggest a survival advantage for breast conserving surgery (BCS) with radiotherapy (BCT). This study assesses the impact of type of surgery on overall survival (OS), breast cancer specific survival (BCSS) and local recurrence (LR) in a modern population-based cohort.

Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis.

Background: Data guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment.

Materials And Methods: There were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT).

Risk of recurrence and pregnancy outcomes in young women with breast cancer who do and do not undergo fertility preservation.

Purpose: To assess the impact of fertility preservation (FP) requiring ovarian stimulation on breast cancer outcomes and pregnancy after breast cancer.

Methods: Women aged ≤ 40 years diagnosed with stage I-III breast cancer between 2007 and 2018 and referred for FP consultation prior to systemic therapy were identified from a British Columbia fertility center database. The primary endpoint was invasive breast cancer-free survival (iBCFS) and secondary endpoints were overall survival (OS) and achievement of pregnancy.

Personalizing Adjuvant Endocrine Therapy for Early-Stage Hormone Receptor-Positive Breast Cancer.

Endocrine therapy has undergone major changes in the past few years, and is no longer a "one- size- fits- all" prescription. This article discussed some of the new developments and directions.

pN0(i+) and pN1mi Breast Cancer: Treatment and Outcomes in Comparison With pN0 and pN1a in the Modern Era.

Purpose: Locoregional recurrence risk and the role of locoregional radiation therapy (LRRT) in pN0(i+) and pN1mi breast cancer are unclear. This study compares locoregional relapse-free survival (LRRFS) in patients with pN0(i+) and pN1mi relative to pN0 and pN1a disease and evaluates LRRFS according to locoregional treatment.

Methods And Materials: We studied 10,271 patients referred between 2006 and 2011 with newly diagnosed pT1-T2, pN0, pN0(i+), pN1mi, or pN1a, M0 breast cancer.

Impact of TAILORx on chemotherapy prescribing and 21-gene recurrence score-guided treatment costs in a population-based cohort of patients with breast cancer.

Background: The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined.

Methods: The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019).

Association Between Regional Nodal Irradiation and Breast Cancer Recurrence-Free Interval for Patients With Low-Risk, Node-Positive Breast Cancer.

Purpose: Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population.

Breast Tangent Beam Energy, Surgical Bed-to-Skin Distance and Local Recurrence After Breast-Conserving Treatment.

Purpose: Higher energy (>6 MV) photons reduce dose inhomogeneity with breast tangent beams, thereby reducing late breast toxicity, but skin and superficial tissue sparing by higher energy beams raises concerns about local recurrence (LR) risk. This study aimed to determine whether beam energy and surgical bed-to-skin distance affect LR.

Methods And Materials: This population-based study included newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with breast-conserving surgery and adjuvant whole breast radiation therapy without bolus or beam spoilers.

Impact of the 21-Gene Recurrence Score Assay on the Treatment of Estrogen Receptor-Positive, HER2-Negative, Breast Cancer Patients With 1-3 Positive Nodes: A Prospective Clinical Utility Study.

Purpose: The use of the 21-gene Recurrence Score (RS) assay is emerging in node-positive estrogen receptor (ER)+ HER2-negative breast cancer (BC), particularly as initial data from the RxPONDER trial are now available. We investigated the impact of the RS result on adjuvant treatment decisions in such patients.

Patients And Methods: This prospective, multi-center study enrolled patients with ER+, HER2-negative BC and 1 to 3 positive nodes (microscopic [N1mi] or macroscopic [N1]).

The cost-effectiveness of adding tomosynthesis to mammography-based breast cancer screening: an economic analysis.

Background: Observational studies show that digital breast tomosynthesis (DBT) combined with digital mammography (DM) can reduce recall rates and increases rates of breast cancer detection. The objective of this study was to examine the cost-effectiveness of DBT plus DM versus DM alone in British Columbia and to identify parameters that can improve the efficiency of breast cancer screening programs.

Methods: We conducted an economic analysis based on data from a cohort of screening participants in the BC Cancer Breast Screening Program.

Sentinel Node Biopsy Should Not be Routine in Older Patients with ER-Positive HER2-Negative Breast Cancer Who Are Willing and Able to Take Hormone Therapy.

Background: The SSO Choosing Wisely campaign recommended selective sentinel lymph node biopsy (SLNB) in clinically node-negative women aged ≥ 70 years with ER+ breast cancer. We sought to assess the association of SLNB positivity, adjuvant treatment, and survival in a population-based cohort.

Patients And Methods: Women aged ≥ 70 years treated for ER+ HER2- breast cancer between 2010 and 2016 were identified in our prospective provincial database.

The Effect of Bolus on Local Control for Patients Treated With Mastectomy and Radiation Therapy.

Purpose: Bolus use during postmastectomy radiation therapy doubles the risk of grade 2 and 3 skin toxicity. Despite its unknown benefit, bolus is often prescribed during postmastectomy radiation therapy for patients without skin involvement.

Methods And Materials: For women with breast cancer receiving photon 3-dimensional conformal radiation therapy, bolus was used routinely for chest walls but was omitted for breast reconstructions by about half of radiation oncologists from 2007 to 2011.

Breast Cancer Molecular Subtype as a Predictor of Radiation Therapy Fractionation Sensitivity.

Purpose: The predictive benefit of breast cancer molecular subtypes for systemic therapy approaches has been well established; yet, there is a paucity of data regarding their use as a predictor of radiation therapy fractionation sensitivity. The purpose of this study was to determine whether rates of local recurrence (LR) for patients treated with hypofractionated (HF) radiation therapy, in comparison to conventional fractionation, differ across breast cancer molecular subtypes in a large, prospectively collected cohort treated with modern systemic therapy.

Methods And Materials: Patients who received a diagnosis of stage I-III breast cancer between 2005 and 2009 were identified.

Hypofractionated Adjuvant Radiation Therapy Is Effective for Patients With Lymph Node-Positive Breast Cancer: A Population-Based Analysis.

Purpose: This study evaluated long-term, population-based, breast cancer-specific outcomes in patients treated with radiation therapy (RT) to the breast/chest wall plus regional nodes using hypofractionated (HF) (40-42.5 Gy/16 fractions) versus conventionally fractionated (CF) regimens (50-50.4 Gy/25-28 fractions).

Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer: A Phase 1 and Randomized Phase 2 Trial.

Importance: ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life.

Objective: To determine maximum tolerated doses (MTDs) of trastuzumab emtansine (T-DM1) plus capecitabine in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) (phase 1) and the efficacy and safety of this combination vs T-DM1 alone in patients with mBC (phase 2).

Design, Setting, And Participants: The MTD in phase 1 was assessed using a 3 + 3 design with capecitabine dose modification.

Do surgeons convey all the details? A provincial assessment of operative reporting for breast cancer.

Introduction: A breast cancer synoptic operative report was developed using a modified Delphi process METHODS: Data from the British Columbia Cancer Breast Cancer Outcomes Unit (BCOU) was used to analyze the association between the completion of a synoptic operative report and reporting of operative details and The American Society of Breast Surgeons quality indicators.

Results: 3662 patients had surgery for breast cancer by 185 surgeons. 2281 reports were narrative and 1007 synoptic.

The impact of new systemic therapies on survival and time on hormonal treatment in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: A population-based study in British Columbia from 2003 to 2013.

Background: The purpose of this study was to determine whether new systemic therapy regimens have resulted in improved survival and increased time on first- and second-line hormonal treatment for patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) over time.

Methods: Patients diagnosed with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative MBC were identified across 3 time cohorts (2003-2005, 2007-2009, and 2011-2013). Data were prospectively collected.

Mammographic density parameters and breast cancer tumor characteristics among postmenopausal women.

Purpose: Mammographic density is an important breast cancer risk factor, although it is not clear whether the association differs across breast cancer tumor subtypes. We examined the association between indicators of mammographic density and breast cancer risk by tumor subtype among postmenopausal women by investigating heterogeneity across tumor characteristics.

Methods: Mammographic density measures were determined for 477 breast cancer cases and 588 controls, all postmenopausal, in Vancouver, British Columbia, using digitized screening mammograms and Cumulus software.

Base excision repair deficiency signatures implicate germline and somatic aberrations in pancreatic ductal adenocarcinoma and breast cancer oncogenesis.

We report a case of early-onset pancreatic ductal adenocarcinoma in a patient harboring biallelic germline mutations, whose tumor featured somatic mutational signatures consistent with defective -mediated base excision repair and the associated driver transversion mutation p.Gly12Cys. Analysis of an additional 730 advanced cancer cases ( = 731) was undertaken to determine whether the mutational signatures were also present in tumors from germline heterozygote carriers or if instead the signatures were only seen in those with biallelic loss of function.