Assessment of HER2 using the 2018 ASCO/CAP guideline update for invasive breast cancer: a critical look at cases classified as HER2 2+ by immunohistochemistry

Taylor, Valerie Jones; Barnes, Penny J.; Godwin, Sean C.; Bethune, Gillian C.

doi:10.1007/s00428-021-03034-4

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…Of the HER2 IHC score = 2+ breast carcinomas referred for FISH in our study, 11.2% were confirmed FISH-positive and 81.7% were FISH-negative, as per the HER2 FISH report at the time of diagnosis. This is lower than the HER2 FISH-positive rates reported by Taylor et al 9 (23.3%), Efared et al 10 (22.5%), and Payandeh et al 11 (31%) described in Canada, Morocco and Iran, respectively. The lower FISH positivity observed in our study may be due to a number of factors, including tissue fixation, interobserver variability with HER2 IHC interpretation, study population differences, and difficulties interpreting FISH signals.…”

Section: Discussioncontrasting

confidence: 55%

HER2 Equivocal (Score = 2+) Breast Carcinoma Cases Identified by Immunohistochemistry at a South African Hospital. What is the Impact of Fluorescent In Situ Hybridization Testing?

Mohanlal

Bouwer

Willem

2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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The American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) guidelines are used for human epidermal growth factor receptor 2 (HER2) reporting in breast carcinoma. Cases that demonstrate weak to moderate complete membrane immunohistochemical staining in >10% of the tumor are scored as 2+ (equivocal). This study aimed to determine what proportion of HER2 immunohistochemistry (IHC) score = 2+ breast carcinomas were confirmed to be positive by HER2 fluorescent in situ hybridization (FISH). There were 241 HER2 IHC score = 2+ breast carcinomas included. Most (74.3%) carcinomas were estrogen and progesterone receptor-positive. Invasive breast carcinoma of no special type (89.2%) was the commonest histologic subtype. Most tumors were grade 2 (64.3%). As per the FISH report, at the time of diagnosis, 27 cases (11.2%) were HER2 FISH positive. All HER2 FISH equivocal cases and one FISH positive case assessed using the 2013 ASCO/CAP HER2 criteria were reclassified to HER2 FISH negative when the 2018 criteria were applied. There was a high level of agreement (κ = 0.979) between HER2 FISH results obtained using the 2013 and the 2018 criteria. This study provides insight into the frequency of HER2 FISH positivity (11.2%) among HER2 IHC score = 2+ breast carcinomas and the impact of modifications to the ASCO/CAP HER2 guidelines. Elimination of the HER2 FISH equivocal category by the 2018 guidelines has reduced the need for repeat testing and simplified clinical management. Reclassification of previous HER2 FISH positive to negative has resulted in some patients being ineligible for costly anti-HER therapy.

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Section: Discussioncontrasting

confidence: 55%

HER2 Equivocal (Score = 2+) Breast Carcinoma Cases Identified by Immunohistochemistry at a South African Hospital. What is the Impact of Fluorescent In Situ Hybridization Testing?

Mohanlal

Bouwer

Willem

2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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“…For IHC score 0 and 1 + or score 2 + with a negative ISH assay, HER2 was considered negative. [ 30 ] Ki67 expression was considered positive when there were at least 14% positive tumor cells. [ 31 ]…”

Section: Methodsmentioning

confidence: 99%

Concordance of RT-qPCR with immunohistochemistry and its beneficial role in breast cancer subtyping

Li,

Chen,

et al. 2023

Medicine

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This study was to compare the concordance of transcription-quantitative polymerase chain reaction (RT-qPCR) with immunohistochemistry (IHC) in determining estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and tumor proliferation index (Ki67) status in breast cancer, and to assess the prognosis based on different subtypes. Totally 323 breast cancer patients were selected, including 216 in the training set and 107 in the validation set. Logistic regression models were constructed using 5-fold cross-validation with the mRNA expression of each biomarker as the predictor and the corresponding IHC expression level as the binary response variable. Receiver operating characteristic curve was used to determine the cutoff value. When the thresholds of ER, PR, HER2, and Ki67 were 0.764, 0.709, 0.161, and 0.554, there existed high concordance rates between IHC and RT-qPCR in ER (94.4%), PR (88.0%) and HER2 (89.4%) and a medium concordance rate in Ki67 (67.8%), which were further confirmed in the validation set (ER: 81.3%, PR: 78.3%, HER2: 80.4%, and Ki67: 69.1%). Based on the subtyping stratified by RT-qPCR, the 5-year recurrence-free interval rates of patients with luminal, HER2-enriched, and triple-negative subtypes were 88% (95% CI: 0.84-0.93), 82% (95% CI: 0.73-0.92) and 58% (95% CI: 0.42-0.80), respectively, which were similar to those assessed by IHC (88%, 78% and 47%). RT-qPCR may be a complementary method to IHC, which can not only provide additional useful information in clinic, but also show more advantages over IHC in determining certain subtypes of breast cancer.

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“…Human epidermal growth factor receptor-2 (HER-2) was tested using immune histochemical staining (IHC) and tumor cells were considered positive with +3 staining, negative with scores of 0 or +1 while those with +2 scores were considered equivocal, for which fluorescence in situ hybridization (FISH) was performed. 27 ER or PR were defined as positive if tumor cell nuclei staining is ≥1%. Clinical and pathological characteristics of the tumors were obtained from patients' electronic medical records.…”

Section: Methodsmentioning

confidence: 99%

Patterns and Prevalence of BRCA1 and BRCA2 Germline Mutations Among Patients with Triple-Negative Breast Cancer: Regional Perspectives

Abdel‐Razeq¹,

Tamimi²,

Abujamous³

et al. 2021

CMAR

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Background: Among all subtypes, patients with triple-negative (TN) breast cancer is known for their poor outcome and their higher risk of harboring BRCA1 or BRCA2 pathogenic mutations. Identification of such mutations has clinical impact on breast and ovarian cancer prevention and treatment decisions. We here report on patterns and prevalence of BRCA1 and BRCA2 mutations among Arab patients diagnosed with TN subtype. Patients and Methods: Patients with TN-breast cancer (n=197) were enrolled regardless of their age or family history. Following a detailed genetic counseling, BRCA1/2 testing was performed at reference labs. BRCA1 and BRCA2 variants were classified as negative, pathogenic/likely pathogenic (positive) and variants of uncertain significance (VUS). Results: Median age of enrolled patients was 42 (range, 19-74) years and 27 (13.7%) were non-Jordanian Arabs. Among the study group, 50 (25.4%) were tested positive for BRCA1 (n=36, 18.3%) or BRCA2 (n=14, 7.1%), while 14 (7.1%) others had VUS. Compared to older ones, mutation rates were higher among patients <40 years (32.9%, P= 0.034), those with close relatives with breast, ovarian, pancreatic or prostate cancer (37.8%, P=0.002) and those with two or more breast cancers (41.4%, P=0.032). Among eligible patients, 23 (63.9%) patients underwent prophylactic mastectomy, while 19 (52.8%) patients had risk-reducing salpingo-oophorectomy. None of the patients with VUS underwent any prophylactic surgery. Conclusion:Arab patients with TN-breast cancer have relatively high BRCA1 or BRCA2 mutation rates. Young age at diagnosis and personal and family history of breast cancer further increase this risk.

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Assessment of HER2 using the 2018 ASCO/CAP guideline update for invasive breast cancer: a critical look at cases classified as HER2 2+ by immunohistochemistry

Cited by 6 publications

References 32 publications

HER2 Equivocal (Score = 2+) Breast Carcinoma Cases Identified by Immunohistochemistry at a South African Hospital. What is the Impact of Fluorescent In Situ Hybridization Testing?

HER2 Equivocal (Score = 2+) Breast Carcinoma Cases Identified by Immunohistochemistry at a South African Hospital. What is the Impact of Fluorescent In Situ Hybridization Testing?

Concordance of RT-qPCR with immunohistochemistry and its beneficial role in breast cancer subtyping

Patterns and Prevalence of BRCA1 and BRCA2 Germline Mutations Among Patients with Triple-Negative Breast Cancer: Regional Perspectives

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