Two of the most important prognostic indicators for breast cancer are tumor size and extent of axillary lymph node involvement. Data on 24,740 cases recorded in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were used to evaluate the breast cancer survival experience in a representative sample of women from the United States. Actuarial (life table) methods were used to investigate the 5-year relative survival rates in cases with known operative/pathologic axillary lymph node status and primary tumor diameter. Survival rates varied from 45.5% for tumor diameters equal to or greater than 5 cm with positive axillary nodes to 96.3% for tumors less than 2 cm and with no involved nodes. The relation between tumor size and lymph node status was investigated in detail. Tumor diameter and lymph node status were found to act as independent but additive prognostic indicators. As tumor size increased, survival decreased regardless of lymph node status; and as lymph node involvement increased, survival status also decreased regardless of tumor size. A linear relation was found between tumor diameter and the percent of cases with positive lymph node involvement. The results of our analyses suggest that disease progression to distant sites does not occur exclusively via the axillary lymph nodes, but rather that lymph node status serves as an indicator of the tumor's ability to spread.

Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

The number of druggable tumor-specific molecular aberrations has grown substantially in the past decade, with a significant survival benefit obtained from biomarker matching therapies in several cancer types. Molecular pathology has therefore become fundamental not only to inform on tumor diagnosis and prognosis but also to drive therapeutic decisions in daily practice. The introduction of next-generation sequencing technologies and the rising number of large-scale tumor molecular profiling programs across institutions worldwide have revolutionized the field of precision oncology. As comprehensive genomic analyses become increasingly available in both clinical and research settings, healthcare professionals are faced with the complex tasks of result interpretation and translation. This review summarizes the current and upcoming approaches to implement precision cancer medicine, highlighting the challenges and potential solutions to facilitate the interpretation and to maximize the clinical utility of molecular profiling results. We describe novel molecular characterization strategies beyond tumor DNA sequencing, such as transcriptomics, immunophenotyping, epigenetic profiling, and single-cell analyses. We also review current and potential applications of liquid biopsies to evaluate blood-based biomarkers, such as circulating tumor cells and circulating nucleic acids. Last, lessons learned from the existing limitations of genotype-derived therapies provide insights into ways to expand precision medicine beyond genomics.

https://tspace.library.utoronto.ca/bitstream/1807/99046/1/13073_2019_Article_703.pdf

Molecular profiling for precision cancer therapies.

Background The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network. Materials and methods Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit. They underwent comprehensive next generation sequencing (NGS) of either tumour tissue or cell-free circulating tumour DNA (ctDNA) or both. The MTB expressed either a positive or negative opinion for the treatment of the patients with discovered druggable alterations inside a clinical trial, in an expanded access programme, with a compassionate use. Afterwards, discovered alterations were matched with OncoKB levels of evidence for the choice of alteration-specific treatments in order to compare MTB outcomes with a standardised set of recommendations. Results NGS was performed either on ctDNA or tumour tissue or in both of them in 204 patients. The MTB evaluated 173 of these cases. Overall, the MTB proposed alteration-specific targeted therapy to 72 patients (41.6%). 49 patients (28.3% of the total evaluated) were indicated to enter a clinical trial. In 29 patients with matched liquid biopsy NGS (lbNGS), tumour tissue NGS (ttNGS) and MTB evaluation, the MTB changed the treatment strategy coming from standardised recommendations based on lbNGS and ttNGS alone in 10 patients (34.5%), thanks to the evaluation of other clinical parameters. In our cohort, lbNGS was more likely, compared with ttNGS, to detect point mutations (OR 11, 95% CI 2.9 to 24.1, p Conclusions Our MTB allows patients with refractory cancer to be included in clinical trials and improves the precision of clinical decisions compared with a standardised set of mutation-driven recommendations.

https://biblio.ugent.be/publication/8688023/file/8707909.pdf

Multidisciplinary molecular tumour board: a tool to improve clinical practice and selection accrual for clinical trials in patients with cancer.

Objectives Scalable informatics solutions that provide molecularly tailored treatment recommendations to clinicians are needed to streamline precision oncology in care settings. Materials and methods We developed a cloud-based virtual molecular tumor board (VMTB) platform that included a knowledgebase, scoring model, rules engine, an asynchronous virtual chat room and a reporting tool that generated a treatment plan for each of the 1725 patients based on their molecular profile, previous treatment history, structured trial eligibility criteria, clinically relevant cancer gene-variant assertions, biomarker-treatment associations, and current treatment guidelines. The VMTB systematically allows clinician users to combine expert-curated data and structured data from clinical charts along with molecular testing data to develop consensus on treatments, especially those that require off-label and clinical trial considerations. Results The VMTB was used as part of the cancer care process for a focused subset of 1725 patients referred by advocacy organizations wherein resultant personalized reports were successfully delivered to treating oncologists. Median turnaround time from data receipt to report delivery decreased from 14 days to 4 days over 4 years while the volume of cases increased nearly 2-fold each year. Using a novel scoring model for ranking therapy options, oncologists chose to implement the VMTB-derived therapies over others, except when pursuing immunotherapy options without molecular support. Discussion VMTBs will play an increasingly critical role in precision oncology as the compendium of biomarkers and associated therapy options available to a patient continues to expand. Conclusion Further development of such clinical augmentation tools that systematically combine patient-derived molecular data, real-world evidence from electronic health records and expert curated knowledgebases on biomarkers with computational tools for ranking best treatments can support care pathways at point of care.

/pdf/a-virtual-molecular-tumor-board-to-improve-efficiency-and-5fen0bifoc.pdf

A virtual molecular tumor board to improve efficiency and scalability of delivering precision oncology to physicians and their patients.

Purpose This study aimed to investigate the predictive role of lymph nodes (LNs) and assess the prognostic significance of the ratio of positive LNs (LNR) and log odds of positive LNs (LODDS) in breast cancer patients who have undergone a mastectomy. Patients and methods All of the breast cancer patients in the Taiwan Cancer Database during 2002–2006 were considered. We excluded patients who had inflammatory breast cancer, stage 0 and IV disease, breast conservative surgery or survival 2 (R 2 N ) and receiver operating characteristics (ROC). Results A total of 11,349 (6042 node-negative, 5307 node-positive) patients were enrolled, and 10.5% patients had a limited number of LNs harvested. In a multivariate Cox model, LNR and LODDS demonstrated prognostic significance ( P 2 N  = 18.2%) when sufficient LNs were examined. However, a model with LODDS showed the best fit in patients with a limited number of LNs harvested ( P 2 N  = 21.1%), even in node-negative patients (P = 0.004; R 2 N  = 13.5%). The area under the ROC curve (AUC) was highest for LODDS (AUC: 0.761), followed by LNR (AUC: 0.757). A limited LN harvest induced an AUC value for an approximate 3.6% loss (LNR) or 3.1% loss (LODDS). Conclusion The prognostic superiority of LNR is confounded by a limited LN harvest, thus making LODDS the most powerful and unified prognostic classifier in breast cancer patients who have had a mastectomy.

Ratio and log odds of positive lymph nodes in breast cancer patients with mastectomy.

PurposeMultidisciplinary tumor boards (MTBs) have become commonplace. The use, attendance, and function of MTBs need continued assessment and improvement.MethodsWe prospectively recorded and assessed all cases presented at MTBs between October 2013 and December 2014. Data were collected before and during each MTB. Data were analyzed using SPSS for Windows version 23 (SPSS, Chicago, IL).ResultsFive hundred three cases were presented: 234 cases (46%) at GI cancer MTBs, 149 cases (29.6%) at breast cancer MTBs, 69 cases (13.7%) at thoracic/head and neck cancer MTBs, and 51 cases (10.7%) at neuro-oncology MTBs. A total of 86.7% of MTB cases were presented to make plans for management. Plans for upfront management were made in 67% of the breast cancer cases, 63% of GI cases, 59% of thoracic/head and neck cases, and 49% of neuro-oncology cases. Three hundred ninety-four cases (78.3%) were presented by medical oncologists, whereas only 74 cases (14.7%) were presented by surgeons, and 10 cases (2%) were presented ...

Practice and Impact of Multidisciplinary Tumor Boards on Patient Management: A Prospective Study

Background
The status of the axillary lymph nodes in nonmetastatic lymph node-positive breast cancer (BC) patients remains the single most important determinant of overall survival (OS). Although the absolute number of nodes involved with cancer is important for prognosis, the role of the total number of excised nodes has received less emphasis. Thus, several studies have focused on the utility of the axillary lymph node ratio (ALNR) as an independent prognostic indicator of OS. However, most studies suffered from shortcomings, such as including patients who received neoadjuvant therapy or failing to consider the use of adjuvant therapy and tumor receptor status in their analysis.

Ratio Between Positive Lymph Nodes and Total Excised Axillary Lymph Nodes as an Independent Prognostic Factor for Overall Survival in Patients with Nonmetastatic Lymph Node-Positive Breast Cancer

/pdf/ratio-between-positive-lymph-nodes-and-total-excised-12laltvi7x.pdf

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.

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Practice and Impact of Multidisciplinary Tumor Boards on Patient Management: A Prospective Study

Ratio Between Positive Lymph Nodes and Total Excised Axillary Lymph Nodes as an Independent Prognostic Factor for Overall Survival in Patients with Nonmetastatic Lymph Node-Positive Breast Cancer

Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer.