Recently, clinical trials have demonstrated promising efficacy for novel HER2-targeted therapies in HER2-low breast cancers, raising the prospect of including a HER2-low category (immunohistochemical ...IHC score of 1+, or 2+ with non-amplified in-situ hybridization ISH) in the HER2 evaluation of breast cancers. In order to better understand this newly-proposed HER2 category, we investigated the incidence, HER2 staining patterns, clinicopathologic features, and genomic profile of HER2-low breast cancers. HER2-stained slides of 281 consecutive breast cancers were re-reviewed and the clinicopathologic information, MammaPrint, and BluePrint results of these cases were retrospectively analyzed. HER2-low breast cancers were identified in 31% of cases and were more common in estrogen receptor (ER)-positive than ER-negative breast cancers (33.6% vs 15%, p = 0.017). HER2-low cancers were generally clinical stages I–II (79%), ER-positive (93.1%), had homogenous HER2 staining (59.2%), HER2 IHC score of 1+ (87.4%), ductal phenotype (81.6%), histologic grades of 1 or 2 (94.2%) and luminal molecular subtypes (94.3%). Three HER2-low patients received neoadjuvant chemotherapy and none of them achieved pathologic complete response. When compared to HER2-negative (IHC of 0+) and HER2-positive (IHC of 3+ or IHC of 2+ with amplified ISH) cancers, HER2-low breast cancers had significantly lower Ki-67 (p = 0.03 and p < 0.01, respectively) and higher ER positivity (p = 0.01 and p = 0.03, respectively). HER2-low breast cancers were less likely to be basal molecular subtype when compared to HER2-negative cancers (p < 0.01) and were less likely to have a HER2 molecular subtype when compared to HER2-positive cancers (p < 0.01). When adjusted for ER status, there was no significant difference on all the examined variables between HER2-low and HER2-negative groups. Our study provides valuable baseline characteristics of HER2-low breast cancers deriving from consecutive, real-world cases with a consensus confirmation of HER2 status, and would help to increase our understanding of this newly-proposed HER2 category in breast cancers.
Objectives: Recent clinical trials have demonstrated significant clinical benefits from novel therapeutic compounds in breast cancer patient with human epidermal growth factor receptor 2 (HER2) ...immunohistochemical (IHC) score of 1+ or 2+ and negative in situ hybridization (ISH) result. A new concept of "HER2-low" breast cancer has been proposed and applied in the recent and ongoing clinical trials. In this article, we review the literature on the topic of HER2-low breast cancer. Methods: A literature search in PubMed was performed using key words related to HER2-low breast cancer. Major relevant studies that were presented in international breast cancer conferences were also included. Results: HER2-low breast cancer is currently defined as breast cancer with HER2 IHC score of 1+ or 2+ and negative ISH result. It likely represents a group of tumors with significant biological heterogeneity. Reports of clinical activity using the next generation of HER2-targeting antibody-drug conjugates in HER2-low breast cancers suggest that some strategies of targeting HER2 might be effective in this patient population while raising considerable concerns over limitations in our current testing methodologies and our ability to accurately identify such patients. Conclusions: The promising efficacy of novel HER2-targeted therapy in advanced HER2-low breast cancers has raised the possibility for changing the clinical interpretation of HER2 status in breast cancer to include a HER2-low category; however, the definition of HER2-low breast cancer, the corresponding reliable and accurate quantitative HER2 testing methodology, and the biology of HER2-low breast cancer remain poorly defined. KEY WORDS HER2-low; Breast cancer; HER2-targeted therapy; Antibody-drug conjugate
To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast ...cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.
ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing.
The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations.
The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing. This guideline was developed through a collaboration between the American Society of Clinical Oncology and the College of American Pathologists and has been published jointly by invitation and consent in both Journal of Clinical Oncology and the Archives of Pathology & Laboratory Medicine.
To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast ...cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.
ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing.
The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations.
The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
HER2-Low Breast Cancers Zhang, Huina; Katerji, Hani; Turner, Bradley M ...
American journal of clinical pathology,
2022-Mar-03, 2022-03-03, 20220303, Letnik:
157, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Recent clinical trials have demonstrated significant clinical benefits from novel therapeutic compounds in breast cancer patient with human epidermal growth factor receptor 2 (HER2) ...immunohistochemical (IHC) score of 1+ or 2+ and negative in situ hybridization (ISH) result. A new concept of "HER2-low" breast cancer has been proposed and applied in the recent and ongoing clinical trials. In this article, we review the literature on the topic of HER2-low breast cancer.
A literature search in PubMed was performed using key words related to HER2-low breast cancer. Major relevant studies that were presented in international breast cancer conferences were also included.
HER2-low breast cancer is currently defined as breast cancer with HER2 IHC score of 1+ or 2+ and negative ISH result. It likely represents a group of tumors with significant biological heterogeneity. Reports of clinical activity using the next generation of HER2-targeting antibody-drug conjugates in HER2-low breast cancers suggest that some strategies of targeting HER2 might be effective in this patient population while raising considerable concerns over limitations in our current testing methodologies and our ability to accurately identify such patients.
The promising efficacy of novel HER2-targeted therapy in advanced HER2-low breast cancers has raised the possibility for changing the clinical interpretation of HER2 status in breast cancer to include a HER2-low category; however, the definition of HER2-low breast cancer, the corresponding reliable and accurate quantitative HER2 testing methodology, and the biology of HER2-low breast cancer remain poorly defined.
To provide recommendations on the appropriate use of breast tumor biomarker assay results to guide decisions on systemic therapy for metastatic breast cancer.
A literature search and prospectively ...defined study selection identified systematic reviews, meta-analyses, randomized controlled trials (RCTs), prospective-retrospective studies, and prospective comparative observational studies published from 2006 through September 2014.
The literature search revealed 17 articles that met criteria for further review: 11 studies reporting discordances between primary tumors and metastases in expression of hormone receptors or human epidermal growth factor receptor 2 (HER2), one RCT that addressed the use of a biomarker to decide whether to change or continue a treatment regimen, and five prospective-retrospective studies that evaluated the clinical utility of biomarkers.
In patients with accessible metastases, biopsy for confirmation of disease process and retesting of estrogen receptor, progesterone receptor, and HER2 status should be offered, but evidence is lacking to determine whether changing anticancer treatment on the basis of change in receptor status affects clinical outcomes. With discordance of results between primary and metastatic tissues, the Panel consensus is to use preferentially the estrogen receptor, progesterone receptor, and HER2 status of the metastasis to direct therapy if supported by the clinical scenario and patient's goals for care. Carcinoembryonic antigen, cancer antigen 15-3, and cancer antigen 27-29 may be used as adjunctive assessments, but not alone, to contribute to decisions regarding therapy. Recommendations for tumor rebiopsy and use of circulating tumor markers are based on clinical experience and Panel informal consensus in the absence of studies designed to evaluate the clinical utility of the markers. As such, it is also reasonable for clinicians to not use these markers as adjunctive assessments.
Abstract
Objectives
We assessed the interobserver and interantibody reproducibility of HER2 immunohistochemical scoring in an enriched HER2-low–expressing breast cancer cohort.
Methods
A total of 114 ...breast cancer specimens were stained by HercepTest (Agilent Dako) and PATHWAY anti-HER2 (4B5) (Ventana) antibody assays and scored by 6 breast pathologists independently using current HER2 guidelines. Level of agreement was evaluated by Cohen κ analysis.
Results
Although the interobserver agreement rate for both antibodies achieved substantial agreement, the average rate of agreement for HercepTest was significantly higher than that for the 4B5 clone (74.3% vs 65.1%; P = .002). The overall interantibody agreement rate between the 2 antibodies was 57.8%. Complete interobserver concordance was achieved in 44.7% of cases by HercepTest and 45.6% of cases by 4B5. Absolute agreement rates increased from HER2 0-1+ cases (78.1% by HercepTest and 72.2% by 4B5; moderate agreement) to 2-3+ cases (91.9% by HercepTest and 86.3% by 4B5; almost perfect agreement).
Conclusions
Our results demonstrated notable interobserver and interantibody variation on evaluating HER2 immunohistochemistry, especially in cases with scores of 0-1+, although the performance was much more improved among breast-specialized pathologists with the awareness of HER2-low concept. More accurate and reproducible methods are needed for selecting patients who may benefit from the newly approved HER2-targeting agent on HER2-low breast cancers.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and ...maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.
The molecular classification for breast carcinomas has been used in clinical studies with a simple surrogate panel of immunohistochemistry (IHC) markers. The objective of this current project was to ...study the molecular classification of commonly used breast cancer cell lines by IHC analysis. Seventeen breast cancer cell lines were harvested, fixed in formalin and made into cell blocks. IHC analyses were performed on each cell block with antibodies to estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, CK5/6, Ki-67 and androgen receptor (AR). Among the 17 cell lines, MCF-7 and ZR-75-1 fell to Luminal A subtype; BT-474 to Luminal B subtype; SKBR-3, MDA-MD-435 and AU 565 to HER2 over-expression subtype; MDA-MB-231, MCF-12A, HBL 101, HS 598 T, MCF-10A, MCF-10F, BT-20, 468 and BT-483 to basal subtype. MDA-MB-453 belonged to Unclassified subtype. Since each subtype defined by this IHC-based molecular classification does show a distinct clinical outcome, attention should be paid when choosing a cell line for any study.
With the approval of trastuzumab deruxtecan for treating advanced human epidermal growth factor receptor-2 (HER2) low breast cancer (BC), it has become increasingly important to develop more accurate ...and reliable methods to identify HER2-low BC. In addition, HER2 immunohistochemistry (IHC) has limitations for quantification of HER2. We explored the relationship between HER2 IHC and mRNA levels and evaluated whether HER2 IHC scores and mRNA levels are associated with clinicopathologic features and Oncotype DX Recurrence Score (RS) in estrogen receptor (ER)-positive, HER2-negative BCs. A total of 750 BCs sent for Oncotype DX (ODX) testing were included in this study, and 559 with HER2 mRNA levels were available. There were no statistically significant differences between HER2 0 and HER2-low BC in clinicopathologic variables or ODX RS using HER2 IHC. There was a significant difference in median HER2 mRNA values between HER2 0 and HER2-low (8.7 vs 9.3, P < .001); however, the HER2 mRNA distribution had substantial overlap between these 2 groups with a suboptimal area under the receiver operating characteristic curve (area under the receiver operating characteristic curve = 0.68). A HER2 mRNA value of 9.2 was generated as the optimal cutoff for distinguishing HER2 0 and HER2-low BC. Comparing ER+ BCs with HER2 mRNA high (>9.2) and low (≤9.2) revealed a statistically significant difference in most clinicopathologic variables and ODX RS. From this large cohort of ER-positive, HER2-negative BC, our results demonstrated that HER2 mRNA levels correlated better with clinicopathologic features and recurrence risk as assessed by ODX RS than HER2 IHC scores. Our findings suggest that HER2 mRNA-detecting methods could potentially serve as a quantitative and reliable method for identifying a biologically meaningful group of HER2-low BC. Further study is needed to determine whether HER2 mRNA levels could be more reliable than IHC for identifying which patients will be most likely to benefit from trastuzumab deruxtecan.
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