Molecular Testing in Breast Cancer: A Guide to Current Practices

2016 ◽  
Vol 140 (8) ◽  
pp. 815-824 ◽  
Author(s):  
Ian S. Hagemann
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Molecular Testing ◽  
Breast Cancers ◽  
Nontumor Tissue ◽  
Narrative Literature ◽  
Algorithmic Analysis ◽  
Cancer Specialists ◽  
Narrative Literature Review

Context.—Molecular diagnostics play a role in the management of many cancers, including breast cancer. Objective.—To provide an update on molecular testing in current clinical practice, targeted at practicing pathologists who are not breast cancer specialists. Data Sources.—This study is a narrative literature review. Conclusions.—In addition to routine hormone (estrogen and progesterone) receptor testing, new and recurrent tumors are tested for HER2 amplification by in situ hybridization or overexpression by immunohistochemistry. Intrinsic subtyping of tumors represents a fundamental advance in our understanding of breast cancer biology, but currently it has an indirect role in patient management. Clinical next-generation sequencing (tumor profiling) is increasingly used to identify potentially actionable mutations in tumor tissue. Multianalyte assays with algorithmic analysis, including MammaPrint, Oncotype DX, and Prosigna, play a larger role in breast cancer than in many other malignancies. Given that a proportion of breast cancers are familial, testing of nontumor tissue for cancer predisposition mutations also plays a role in breast cancer care.

Overdiagnosis and Overtreatment of Breast Cancer

2012 ◽  
pp. e40-e45
Author(s):  
Michael Alvarado ◽  
Elissa Ozanne ◽  
Laura Esserman
Keyword(s):  
Breast Cancer ◽  
Lower Risk ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Invasive Cancer ◽  
Molecular Testing ◽  
Low Grade ◽  
Breast Cancers ◽  
Molecular Tests

Overview: Breast cancer is the most common cancer in women. Through greater awareness, mammographic screening, and aggressive biopsy of calcifications, the proportion of low-grade, early stage cancers and in situ lesions among all breast cancers has risen substantially. The introduction of molecular testing has increased the recognition of lower risk subtypes, and less aggressive treatments are more commonly recommended for these subtypes. Mammographically detected breast cancers are much more likely to have low-risk biology than symptomatic tumors found between screenings (interval cancers) or that present as clinical masses. Recognizing the lower risk associated with these lesions and the ability to confirm the risk with molecular tests should safely enable the use of less aggressive treatments. Importantly, ductal carcinoma in situ (DCIS) lesions, or what have been called stage I cancers, in and of themselves are not life-threatening. In situ lesions have been treated in a manner similar to that of invasive cancer, but there is little evidence to support that this practice has improved mortality. It is also being recognized that DCIS lesions are heterogeneous, and a substantial proportion of them may in fact be precursors of more indolent invasive cancers. Increasing evidence suggests that these lesions are being overtreated. The introduction of molecular tests should be able to help usher in a change in approach to these lesions. Reclassifying these lesions as part of the spectrum of high-risk lesions enables the use of a prevention approach. Learning from the experience with active surveillance in prostate cancer should empower the introduction of new approaches, with a focus on preventing invasive cancer, especially given that there are effective, United States Food and Drug Administration (FDA)-approved breast cancer preventive interventions.

scholarly journals Narrative Literature Review on Risk Factors Involved In Breast Cancer, Brain Cancer, Colon Rectal Cancer, Gynecological Malignancy, Lung Cancer, and Prostate Cancer

2021 ◽  
Author(s):  
Angel Justiz-Vaillant ◽  
Lyvan Gardiner ◽  
Maryam Mohammed ◽  
Matthew Surajbally ◽  
Luke Maharaj ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Literature Review ◽  
Brain Cancer ◽  
Gynecological Malignancy ◽  
The Public ◽  
Narrative Literature ◽  
Narrative Literature Review ◽  
Colon Rectal Cancer ◽  
Cancer Côlon

In this study, we describe the most critical risk factors for different malignancies, including breast, prostate, lung, colon-rectal carcinoma, among others and those with risk factors that are modifiable. We revised the literature review about risk factors involved in the genesis of cancer in various databases, including articles indexed in PUBMED, SCOPUS, PMC, and Google Scholar. Knowing risk factors is a mode of fighting malignancy. Diet, lifestyle, practises, and laboratory/clinical interventions were among risk factors of diverse malignancy. We conclude that risk factors can prevent the development of many malignancies in a century where this conundrum is raising disproportionably. It is treated here is to make the public aware of the modifiable risks of cancers.

Surgical Pathology–Based Outcomes Assessment of Breast Cancer Early Diagnosis

2001 ◽  
Vol 125 (3) ◽  
pp. 325-331
Author(s):  
Raouf E. Nakhleh ◽  
Richard J. Zarbo
Keyword(s):  
Breast Cancer ◽  
Health Care ◽  
The United States ◽  
Surgical Pathology ◽  
Detection Methods ◽  
Mortality Data ◽  
Breast Cancers ◽  
Improvement Program ◽  
Clinical Method

Abstract Objective.—To develop breast cancer outcomes data relating pathologic tumor variables at diagnosis with clinical method of detection. Design.—Anatomic pathologists assessed 30 consecutive breast cancers at each institution, resulting in an aggregate database of 4232 breast cancers. Setting.—Hospital-based laboratories from the United States (98%), Canada, Australia, and Belgium. Participants.—One hundred ninety-nine laboratories in the 1999 College of American Pathologists Q-Probes voluntary quality improvement program. Main Outcome Measures.—Pathologic variables indicative of favorable outcomes included percentage of carcinomas detected at the in situ stage, tumors ≤1 cm in diameter, and invasive cancers with lymph nodes negative for metastases. Results.—All outcomes measures, including percent in situ carcinomas (26.9% vs 13.8%), tumor size ≤1 cm (57.8% vs 36.5%), and lymph node–negative status (77.8% vs 64%), were more favorable when tumors were detected by screening mammography (P < .001) compared to all other detection methods. Conclusions.—This study demonstrates an opportunity for pathologists to develop outcomes information of interest to health care organizations, providers, patients, and payers by integrating routine oncologic surgical pathology and clinical breast cancer detection data. Such readily obtained interim outcomes data trended and benchmarked over time can demonstrate the relative clinical efficacy of preventive breast care provided by health care systems long before mortality data are available.

Molecular Testing in Breast Cancer

2019 ◽  
pp. e1-e7 ◽  
Author(s):  
Jennifer K. Litton ◽  
Harold J. Burstein ◽  
Nicholas C. Turner
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Hereditary Cancer ◽  
Standard Of Care ◽  
Genomic Variation ◽  
Advanced Breast ◽  
Hereditary Cancer Syndrome ◽  
Molecular Testing ◽  
Breast Cancers ◽  
Cancer Management

Molecular testing for genetic and genomic variation has become an integral part of breast cancer management. Patients with a family history of breast cancer or other tumors, bilateral breast cancers, or early-onset breast cancers warrant genetic testing to determine whether a hereditary cancer syndrome is present. The availability of PARP inhibitors—drugs that are selectively active in BRCA1/2-associated breast cancers—has created the need for hereditary cancer testing for all patients diagnosed with advanced breast cancer. Tumor genomic profiling is the standard of care for many types of malignancies and is becoming increasingly important in the management of advanced breast cancer. Targetable mutations in advanced breast cancer include PIK3CA, HER2, and rare instances of mismatch deficiency or other targets for tyrosine kinase inhibitors. The development of methods for sequencing cell-free DNA should allow for broader and easier implementation of tumor genomic testing. Transcriptome-based expression signatures have become the standard of care in the management of early-stage estrogen receptor–positive breast cancers. These assays provide prognostic significance in the setting of adjuvant endocrine therapy and are predictive for benefit from adjuvant chemotherapy. Collectively, these developments underscore the contemporary reality that molecular testing is now part of the clinical management for the majority of patients with breast cancer.

HER-2/neu Analysis in Archival Tissue Samples of Human Breast Cancer: Comparison of Immunohistochemistry and Fluorescence In Situ Hybridization

2001 ◽  
Vol 19 (2) ◽  
pp. 354-363 ◽  
Author(s):  
Annette Lebeau ◽  
Daniela Deimling ◽  
Christine Kaltz ◽  
Andrea Sendelhofert ◽  
Anette Iff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Gene Amplification ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Paraffin Sections ◽  
Tissue Samples ◽  
Her 2

PURPOSE: The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH). MATERIALS AND METHODS: HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany). RESULTS: HER-2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification. CONCLUSION: The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification.

American Society of Clinical Oncology/College of American Pathologists 2018 Focused Update of Breast Cancer HER2 FISH Testing GuidelinesResults From a National Reference Laboratory

2019 ◽  
Vol 152 (4) ◽  
pp. 479-485 ◽  
Author(s):  
Leo Lin ◽  
Deepika Sirohi ◽  
Joshua F Coleman ◽  
H Evin Gulbahce
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Reference Laboratory ◽  
National Reference Laboratory ◽  
Breast Cancers ◽  
National Reference ◽  
American Society ◽  
New Guidelines ◽  
Her2 Positivity

Abstract Objectives To review impact of the ASCO/CAP 2018 update on HER2 testing. Methods HER2 fluorescence in situ hybridization (FISH) test requests from primary and metastatic breast cancers between August 2018 and January 2019 were included. FISH results requiring a changed algorithm under the new guidelines (groups 2, 3, and 4) were identified and HER2:CEN17 ratios, average HER2, CEN17 signals/cell, and HER2 immunohistochemistry (IHC) results were recorded. Results Of the HER2 FISH cases 176/812(21.7%) fell within groups 2, 3, or 4; 0/12, 1/12, and 2/152 cases were positive (3+) by IHC, and 1/12, 2/12, and 6/152 cases were positive after targeted scoring from groups 2, 3, and 4, respectively. Following 2018 updates, 8.3%, 25%, and 5.3% of the groups 2, 3, and 4 were positive, respectively. Conclusions Groups 2, 3, and 4 constituted over 20% of HER2 FISH tests in a reference laboratory. The 2018 ASCO/CAP update significantly decreased the HER2 positivity rate.

scholarly journals Distribution of Ki-67 values within HER2 & ER/PgR expression variants of ductal breast cancers as a potential link between IHC features and breast cancer biology

BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Sven Kurbel ◽  
Branko Dmitrović ◽  
Ksenija Marjanović ◽  
Damir Vrbanec ◽  
Antonije Juretić
Keyword(s):  
Breast Cancer ◽  
Cancer Biology ◽  
Breast Cancers ◽  
Ki 67 ◽  
Potential Link

scholarly journals PTHrP Induces STAT5 Activation, Secretory Differentiation and Mammary Tumor Progression

2021 ◽  
Author(s):  
Diego Y. Grinman ◽  
Kata Boras-Granic ◽  
Farzin M. Takyar ◽  
Pamela Dann ◽  
Julie R. Hens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Milk Production ◽  
Mammary Tumor ◽  
Cancer Biology ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Breast Cancers ◽  
The Impact ◽  
Secretory Differentiation

Background: Parathyroid hormone-related protein (PTHrP) is required for embryonic breast development and has important functions during lactation, when it is produced by alveolar epithelial cells and secreted into the maternal circulation to mobilize skeletal calcium used for milk production. PTHrP is also produced by breast cancers and GWAS studies suggest that it influences breast cancer risk. However, the exact functions of PTHrP in breast cancer biology remain unsettled. Methods: We developed a tetracyline-regulated, MMTV (mouse mammary tumor virus)-driven model of PTHrP overexpression in mammary epithelial cells (Tet-PTHrP mice) and bred these mice with the MMTV-PyMT (polyoma middle tumor-antigen) breast cancer model to analyze the impact of PTHrP overexpression on normal mammary gland biology and in breast cancer progression. Results: Overexpression of PTHrP in luminal epithelial cells caused alveolar hyperplasia and secretory differentiation of the mammary epithelium with milk production. This was accompanied by activation of Stat5 and increased expression of E74-like factor-5 (Elf5). In MMTV-PyMT mice, overexpression of PTHrP (Tet-PTHrP;PyMT mice) shortened tumor latency and accelerated tumor growth, ultimately reducing overall survival. Tumors overproducing PTHrP also displayed increased expression of nuclear pSTAT5 and Elf5, increased expression of markers of secretory differentiation and milk constituents, and histologically resembled secretory carcinomas of the breast. Overexpression of PTHrP within cells isolated from tumors, but not PTHrP exogenously added to cell culture media, led to activation of STAT5 and milk protein gene expression. In addition, neither ablating the Type 1 PTH/PTHrP receptor (PTH1R) in epithelial cells or treating Tet-PTHrP;PyMT mice with an anti-PTH1R antibody prevented secretory differentiation or altered tumor latency. These data suggest that PTHrP acts in a cell-autonomous, intracrine manner. Finally, expression of PTHrP in human breast cancers is associated with expression of genes involved in milk production and STAT5 signaling. Conclusions: Our study suggests that PTHrP promotes pathways leading to secretory differentiation and proliferation in both normal mammary epithelial cells and in breast tumor cells.

scholarly journals Impact of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 Guideline Updates on HER2 Assessment in Breast Cancer With Equivocal HER2 Immunohistochemistry Results With Focus on Cases With HER2/CEP17 Ratio <2.0 and Average HER2 Copy Number ≥4.0 and <6.0

2019 ◽  
Vol 144 (5) ◽  
pp. 597-601 ◽  
Author(s):  
Raza S. Hoda ◽  
Edi Brogi ◽  
Jin Xu ◽  
Katia Ventura ◽  
Dara S. Ross ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Clinical Oncology ◽  
Copy Number ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
American Society ◽  
Dual Probe

Context.— The American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline in breast cancer was updated in 2018 to address issues on interpretation of uncommon results using dual-probe in situ hybridization according to the 2013 guideline. Objective.— To assess impact of the 2018 guideline on breast cancer with equivocal HER2 immunohistochemistry results. Design.— We retrospectively reviewed HER2 fluorescence in situ hybridization (FISH) data (HER2/CEP17 ratio and average HER2 copy number per cell) of HER2 immunohistochemistry–equivocal (2+ or 1+ to 2+) breast cancers at our center between January 2014 and May 2018 and compared HER2 FISH results according to 2013 and 2018 guidelines. Results.— A total of 1666 HER2 FISH results from 1421 patients with equivocal HER2 immunohistochemistry were reviewed. Based on the 2013 guideline, HER2 FISH results were amplified in 346 cases (20.8%), equivocal in 242 (14.5%), and nonamplified in 1078 (64.7%). Using the 2018 guideline, 258 cases (16%) were reclassified, including 242 previously equivocal test results (15%) and 16 previously positive results (1%) reclassified as negative. The subset of 2013 HER2-equivocal and 2018 HER2-nonamplified cases with HER2/CEP17 ratio lower than 2.0 and average HER2 copy number 4.0 or higher and lower than 6.0 showed higher incidence of micropapillary morphology compared with HER2-amplified cases. Despite most patients in this group not receiving HER2-targeted treatment, 96% had no evidence of disease at follow-up. Conclusions.— The 2018 guideline eliminated HER2 FISH–equivocal cases by reclassifying HER2-equivocal cases and cases with nonclassical amplification without HER2 overexpression as HER2 negative. As a consequence, we observed a considerable increase in HER2 FISH–negative cases and a slight decrease in HER2 FISH–positive cases.

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