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

Bone is the most common site to which breast cancer metastasizes. Imaging-by skeletal scintigraphy, plain radiography, computed tomography, or magnetic resonance imaging-is an essential part, and positron emission tomography or single-photon emission computed tomography have a potential of evaluating bone metastases, but no consensus exists as to the best modality for diagnosing the lesion and for assessing its response to treatment. Imaging bone metastases is problematic because the lesions can be osteolytic, osteoblastic, or mixed, and imaging modalities are based on either direct anatomic visualization of the bone or tumor or indirect measurements of bone or tumor metabolism. Although bone metastases can be treated, their response to treatment is considered "unmeasurable" according to existing response criteria. Therefore, the process by which oncologists and radiologists diagnose and monitor the response of bone metastases needs revision, and the current inability to assess the response of bone metastases excludes patients with breast cancer and bone disease from participating in clinical trials of new treatments for breast cancer. In this review of the MEDLINE literature, we discuss the pros and cons of each modality for diagnosing bone metastases and for assessing their response to treatment and we present a practical approach for diagnosis and assessment of bone metastasis.

Bone Imaging in Metastatic Breast Cancer

Purpose
The radionuclide bone scan is the cornerstone of skeletal nuclear medicine imaging. Bone scintigraphy is a highly sensitive diagnostic nuclear medicine imaging technique that uses a radiotracer to evaluate the distribution of active bone formation in the skeleton related to malignant and benign disease, as well as physiological processes.

/pdf/the-eanm-practice-guidelines-for-bone-scintigraphy-1ta1gsyfoo.pdf

The EANM practice guidelines for bone scintigraphy

Background:
Breast cancer (BC) accounts for one-third of all cases of cancer in women in the UK. Current strategies for the detection of BC recurrence include computed tomography (CT), magnetic resonance imaging (MRI) and bone scintigraphy. Positron emission tomography (PET) and, more recently, positron emission tomography/computed tomography (PET/CT) are technologies that have been shown to have increasing relevance in the detection and management of BC recurrence.
Objective:
To review the accuracy of PET and PET/CT for the diagnosis of BC recurrence by assessing their value compared with current practice and compared with each other.
Data sources:
MEDLINE and EMBASE were searched from inception to May 2009.
Study selection:
Studies were included if investigations used PET or PET/CT to diagnose BC recurrence in patients with a history of BC and if the reference standard used to define the true disease status was histological diagnosis and/or long-term clinical follow-up. Studies were excluded if a non-standard PET or PET/CT technology was used, investigations were conducted for screening or staging of primary breast cancer, there was an inadequate or undefined reference standard, or raw data for calculation of diagnostic accuracy were not available. STUDY APPRAISAL: Quality assessment and data extraction were performed independently by two reviewers. Direct and indirect comparisons were made between PET and PET/CT and between these technologies and methods of conventional imaging, and meta-analyses were carried out. Analysis was conducted separately on patient- and lesion-based data. Subgroup analysis was conducted to investigate variation in the accuracy of PET in certain populations or contexts and sensitivity analysis was conducted to examine the reliability of the primary outcome measures.
Results:
Of the 28 studies included in the review, 25 presented patient-based data and 7 presented lesion-based data for PET and 5 presented patient-based data and 1 presented patient- and lesion-based data for PET/CT; 16 studies conducted direct comparisons with 12 comparing the accuracy of PET or PET/CT with conventional diagnostic tests and 4 with MRI. For patient-based data (direct comparison) PET had significantly higher sensitivity [89%, 95% confidence interval (CI) 83% to 93% vs 79%, 95% CI 72% to 85%, relative sensitivity 1.12, 95% CI 1.04 to 1.21, p = 0.005] and significantly higher specificity (93%, 95% CI 83% to 97% vs 83%, 95% CI 67% to 92%, relative specificity 1.12, 95% CI 1.01 to 1.24, p = 0.036) compared with conventional imaging tests (CITs)--test performance did not appear to vary according to the type of CIT tested. For patient-based data (direct comparison) PET/CT had significantly higher sensitivity compared with CT (95%, 95% CI 88% to 98% vs 80%, 95% CI 65% to 90%, relative sensitivity 1.19, 95% CI 1.03 to 1.37, p = 0.015), but the increase in specificity was not significant (89%, 95% CI 69% to 97% vs 77%, 95% CI 50% to 92%, relative specificity 1.15, 95% CI 0.95 to 1.41, p = 0.157). For patient-based data (direct comparison) PET/CT had significantly higher sensitivity compared with PET (96%, 95% CI 90% to 98% vs 85%, 95% CI 77% to 91%, relative sensitivity 1.11, 95% CI 1.03 to 1.18, p = 0.006), but the increase in specificity was not significant (89%, 95% CI 74% to 96% vs 82%, 95% CI 64% to 92%, relative specificity 1.08, 95% CI 0.94 to 1.20, p = 0.267). For patient-based data there were no significant differences in the sensitivity or specificity of PET when compared with MRI, and, in the one lesion based study, there was no significant differences in the sensitivity or specificity of PET/CT when compared with MRI.
Limitations:
Studies reviewed were generally small and retrospective and this may have limited the generalisability of findings. Subgroup analysis was conducted on the whole set of studies investigating PET and was not restricted to comparative studies. Conventional imaging studies that were not compared with PET or PET/CT were excluded from the review.
Conclusions:
Available evidence suggests that for the detection of BC recurrence PET, in addition to conventional imaging techniques, may generally offer improved diagnostic accuracy compared with current standard practice. However, uncertainty remains around its use as a replacement for, rather than an add-on to, existing imaging technologies. In addition, PET/CT appeared to show clear advantage over CT and PET alone for the diagnosis of BC recurrence. FUTURE WORK: Future research should include: prospective studies with patient populations clearly defined with regard to their clinical presentation; a study of diagnostic accuracy of PET/CT compared with conventional imaging techniques; a study of PET/CT compared with whole-body MRI; studies investigating the possibility of using PET/CT as a replacement for rather than an addition to CITs; and using modelling of the impact of PET/CT on patient outcomes to inform the possibility of conducting large-scale intervention trials.

/pdf/a-systematic-review-of-positron-emission-tomography-pet-and-4nqw2287am.pdf

A systematic review of positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) for the diagnosis of breast cancer recurrence

Glucose Metabolism in Cancer EVIDENCE THAT DEMETHYLATION EVENTS PLAY A ROLE IN ACTIVATING TYPE II HEXOKINASE GENE EXPRESSION

The presence of distant metastases is the main prognostic factor in patients with breast cancer and has a significant influence in the choice of therapy. Therefore, chest X-ray, bone scintigraphy and ultrasound of the abdomen are performed to detect distant metastases at diagnosis and follow-up. Fluorodeoxyglucose positron emission tomography (FDG PET) has been shown to provide sensitive detection of primary tumour and metastases for many tumour entities, but little information is available about the diagnostic value for breast cancer patients. This study retrospectively compared FDG PET for detection of metastatic disease with chest X-ray, bone scintigraphy and ultrasound of the abdomen, referred to as "conventional diagnostic procedures" (CDPs), in 50 breast cancer patients. Imaging procedures were analysed in a blinded fashion with the results classified as "no evidence of metastases", "equivocal" and "evidence of metastases". Clinical follow-up and the results of other imaging modalities including computed tomography and magnetic resonance imaging were used to determine if metastases were present. FDG PET identified metastatic disease with a sensitivity and specificity of 86% and 90% as compared to 36% and 95% for CDPs, respectively. Regarding "equivocal" and "evidence of metastases" as positive, the sensitivity of CDPs increased to 57% with a corresponding specificity of 81%, whereas sensitivity and specificity of FDG PET remained unchanged. Regarding different localities of metastases the sensitivity of FDG PET was superior in the detection of pulmonary metastases and especially of lymph node metastases of the mediastinum in comparison to chest X-ray, whereas the sensitivity of FDG PET in the detection of bone and liver metastases was of the same magnitude as compared with bone scintigraphy and ultrasound of the abdomen.

Comparison of fluorodeoxyglucose positron emission tomography and "conventional diagnostic procedures" for the detection of distant metastases in breast cancer patients.

http://www.thelancet.com/article/S2352396422003747/pdf

Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses

Figure S1. Figure S2. Table S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. 

High concordance of clone detection between peripheral blood and bone marrow by targeted next-generation sequencing-A pilot study in patients with MDS.

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Comparison of fluorodeoxyglucose positron emission tomography and "conventional diagnostic procedures" for the detection of distant metastases in breast cancer patients.

Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses

High concordance of clone detection between peripheral blood and bone marrow by targeted next-generation sequencing-A pilot study in patients with MDS.