scholarly journals Clinical Overestimation of HER2 Positivity in Early Estrogen and Progesterone Receptor–Positive Breast Cancer and the Value of Molecular Subtyping Using BluePrint

2017 ◽  
Vol 3 (4) ◽  
pp. 314-322 ◽  
Author(s):  
Ettienne J. Myburgh ◽  
Lizanne Langenhoven ◽  
Kathleen A. Grant ◽  
Lize van der Merwe ◽  
Maritha J. Kotze
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Molecular Subtype ◽  
Chromosome 17 ◽  
Her2 Status ◽  
Luminal A ◽  
Her2 Positive ◽  
Molecular Subtyping ◽  
Predictive Values ◽  
Her2 Positivity

Purpose Human epidermal growth factor receptor 2 (HER2) positivity is an important prognostic and predictive indicator in breast cancer. HER2 status is determined by immunohistochemistry and fluorescent in situ hybridization (FISH), which are potentially inaccurate techniques as a result of several technical factors, polysomy of chromosome 17, and amplification or overexpression of CEP17 (centromeric probe for chromosome 17) and/or HER2. In South Africa, HER2-positive tumors are excluded from a MammaPrint (MP; Agendia BV, Amsterdam, Netherlands) pretest algorithm. Clinical HER2 status has been reported to correlate poorly with molecular subtype. The aim of this study was to investigate the correlation of clinical HER2 status with BluePrint (BP) molecular subtyping. Methods Clinico-pathologic and genomic information was extracted from a prospectively collected central MP database containing records of 256 estrogen receptor–positive and/or progesterone receptor–positive tumors. Twenty-one tumors considered HER2 positive on immunohistochemistry or FISH were identified for this study. Results The median age of patients was 56 years (range, 34 to 77 years), with a median tumor size of 16 mm (3 to 27 mm). Four (19%) tumors were confirmed HER2-enriched subtype, six (29%) were luminal A, and 11 (52%) were luminal B. The positive predictive values of HER2/CEP17 ratio ≥ 2 and HER2 copy number ≥ 6 were only 29% and 40%, respectively. The differences in means for HER2/CEP17 ratio were significant between BP HER2-enriched versus luminal ( P = .0249; 95% CI, 0.12 to 1.21) and MP high-risk versus low-risk tumors ( P = .0002; 95% CI, 0.40 to 1.06). Conclusion Of the 21 tumors considered clinically HER2 positive, only four were HER2-enriched subtype with BP, indicating an overestimation of HER2 positivity. FISH testing has a poor positive predictive value.

scholarly journals Comparative analysis of the receptor status of the primary focus and synchronous axillary metastases in breast cancer patients

2020 ◽  
Vol 24 (3-6) ◽  
pp. 74-78
Author(s):  
Yu. S. Krumin’ ◽  
V. A. Khailenko ◽  
N. A. Kozlov ◽  
G. Yu. Cheremis ◽  
D. V. Khailenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proliferative Activity ◽  
Molecular Subtype ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Axillary Metastases ◽  
Receptor Status ◽  
Luminal B

The aim of the investigation. To study concordance of surrogate molecular subtype in the pairs of primary and synchronous axillary metastases in patients with invasive breast cancer (IBC). Materials and methods. Retrospective analysis included 80 patients aged 28 to 90 years (average age 40.35.3 years) with a first-time diagnosed IBC who underwent surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology during 20162018 years. None of the patients received any neoadjuvant drug therapy. The pathological evaluation of the estrogen receptors (ER), progesterone receptor (PR), HER2 expression and estimation of proliferative activity (Ki-67 index) with subsequent assignment to surrogate subtypes were performed according to ASCO/CAP protocols and the recommendations of the 20132019 San-Gallen Conference on treatment of Early Breast Cancer. Results. Preliminary results of our study revealed therapeutically significant changes in hormone receptor status, HER2-status and proliferative activity in 12.5% of cases of Luminal A type IBC, 20% of Luminal B/HER2-positive and 4% of Luminal B/Her2-negative subtypes of IBC.

scholarly journals Loss of HER2 Positivity after Trastuzumab in HER2-Positive Gastric Cancer: Is Change in HER2 Status Significantly Frequent?

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yu Ishimine ◽  
Akira Goto ◽  
Yoshito Watanabe ◽  
Hidetaka Yajima ◽  
Suguru Nakagaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gastric Cancer ◽  
Residual Tumor ◽  
Her2 Status ◽  
Resected Specimen ◽  
Her2 Positive ◽  
Curative Intent ◽  
Course Of Disease ◽  
Trastuzumab Therapy ◽  
Her2 Positivity

Trastuzumab has recently been introduced as a treatment for HER2-positive metastatic and/or unresectable gastric cancer (MUGC); however, compared with breast cancer, some issues concerning HER2 and trastuzumab therapy for gastric cancer remain unclear. A 74-year-old woman received trastuzumab-containing chemotherapy for HER2-positive MUGC. She had a marked response to 8 months of chemotherapy, and gastrectomy and hepatic metastasectomy with curative intent were performed. The resected specimen showed complete loss of HER2 positivity in the residual tumor. For MUGC, a change in HER2 status during the course of the disease with or without chemotherapy has rarely been reported. However, in breast cancer, a significant frequency of change in HER2 status during the course of disease has been reported, and reevaluation of HER2 positivity in metastatic/recurrent sites is recommended. The choice of trastuzumab for MUGC is currently based on the HER2 status of the primary tumor at the time of initial diagnosis, without reassessment of HER2 status during the course of disease and/or in metastatic/recurrent sites, on the assumption that HER2 status is stable. However, our case casts doubt on the stability of HER2 in gastric cancer.

Breast cancer in Angola, molecular subtypes: The first preliminary study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Lúcio Lara Santos ◽  
Fernando Miguel ◽  
Lygia Vieira Lopes ◽  
Julio Oliveira ◽  
Eduardo Ferreira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Locally Advanced ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Therapeutic Decisions ◽  
Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

scholarly journals Outcome of HER2 Testing by FISH applying ASCO/CAP 2007 and 2013 guideline in IHC equivocal group of breast cancer: Experience at tertiary cancer care centre

2017 ◽  
Vol 06 (02) ◽  
pp. 045-046
Author(s):  
Manoj Kumar Panigrahi ◽  
Dushyant Kumar ◽  
Anurag Mehta ◽  
Kandarpa Kumar Saikia
Keyword(s):  
Breast Cancer ◽  
Final Analysis ◽  
Chromosome 17 ◽  
Research Centre ◽  
Her2 Status ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Polysomy 17 ◽  
Cancer Experience ◽  
The Impact

Abstract Background and Objectives: HER2 testing guideline of ASCO/CAP for interpretation and reporting has recently been revised. The study is aimed to measure the impact of 2013 CAP guideline on equivocal HER2 test outcome (immunohistochemistry [IHC] 2+) when tested by fluorescent in situ hybridization (FISH). The study also aims at finding the frequency of polysomy and monosomy of chromosome 17. Materials and Methods: Specimens were collected in Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India. IHC was performed in every case, and FISH was performed in IHC2+ cases. Results: In final analysis includes 557 subjects on the basis of CAP guideline 2007 and CAP guideline 2013. One hundred ninety-two subjects (34.4%) were HER2 amplified according to CAP scoring 2007, and 246 subjects (44%) according to 2013 CAP scoring. Conclusions: FISH results were evaluated (IHC2 + interpreted according to CAP 2007 guideline) with both 2007 and 2013 ASCO/CAP scoring criteria, we identified significantly more HER2 positive cases as compared to cases evaluated using the 2007 criteria (P < 0.05). We also found that in breast carcinoma, HER2 status in the presence of polysomy 17 may vary with the scoring criteria used. Evaluation of FISH result using 2013 ASCO/CAP criteria means that more patients with breast cancer may be appropriate for targeted treatment with trastuzumab, potentially improving their outcome.

scholarly journals Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients

2019 ◽  
Vol 7 (21) ◽  
pp. 3534-3539
Author(s):  
Nada A. S. Alwan ◽  
Furat N. Tawfeeq
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Lymph Node Involvement ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Significant Difference

BACKGROUND: Breast cancer remains the most common malignancy among the Iraqi population. Affected patients exhibit different clinical behaviours according to the molecular subtypes of the tumour. AIM: To identify the clinical and pathological presentations of the Iraqi breast cancer subtypes identified by Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions. PATIENTS AND METHODS: The present study comprised 486 Iraqi female patients diagnosed with breast cancer. ER, PR and HER2 contents of the primary tumours were assessed through immunohistochemical staining; classifying the patients into five different groups: Triple Negative (ER/PR negative/HER2 negative), Triple Positive (ER/PR positive/HER2 positive), Luminal A (ER/PR positive/HER2 negative), HER2 enriched ((ER/PR negative/HER2 positive) and all other subtypes. RESULTS: The major registered subtype was the Luminal A which was encountered in 230 patients (47.3%), followed by the Triple Negative (14.6%), Triple Positive (13.6%) and HER2 Enriched (11.5%). Patients exhibiting the Triple Negative subtype were significantly younger than the rest of the groups and presented with larger size tumours. A significant difference in the distribution of the breast cancer stages was displayed (p < 0.05); the most advanced were noted among those with HER2 enriched tumours who exhibited the highest frequency of poorly differentiated carcinomas and lymph node involvement. CONCLUSION: The most significant variations in the clinicopathological presentations were observed in the age and clinical stage of the patients at diagnosis. Adoption of breast cancer molecular subtype classification in countries with limited resources could serve as a valuable prognostic marker in the management of aggressive forms of the disease.

Biological characteristics of oestrogen receptor positive early operable primary breast cancer in the elderly

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10739-10739
Author(s):  
M. W. Ying ◽  
A. R. Green ◽  
A. Agrawal ◽  
C. E. Paish ◽  
D. A. Morgan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Oestrogen Receptor ◽  
The Elderly ◽  
Biological Characteristics ◽  
Her2 Status ◽  
Her2 Positive ◽  
Er Positive ◽  
Her2 Positivity

10739 Background: Over half of breast cancer are diagnosed at >65 years and increasingly more are diagnosed in the elderly population. However little is known about their biological characteristics, which may be important in therapeutic strategies such as selecting endocrine agents as primary, neoadjuvant or adjuvant therapy. We report the pattern of oestrogen receptor (ER), progesterone receptor (PgR) and HER2 status in a cohort of elderly patients with primary breast cancer (PBC). Methods: All elderly (> 70 years) patients, who had ER positive early operable PBC (< 5 cm) and who refused or were unfit for surgery, were treated with primary endocrine therapy. Standard immunohistochemical staining was performed on core biopsy tumour tissuefor ER, PgR and HER2. Positivity for ER and PgR was defined by H-score ≥ 50, and HER2 positivity was defined as 3+. Results: A total of 86 such patients were treated over a two-year period and the biological characteristics of their tumours were as follows (see Table ). Conclusions: Within the group of ER positive patients, approximately half of the tumours also expressed PgR. The total number of HER2 positive tumours was small although the majority of these were PgR negative. Clinical follow-up is ongoing to elucidate the relationship between endocrine sensitivity and these biological characteristics. [Table: see text] [Table: see text]

[18F] Fluorodeoxyglucose positron emission (FDG-PET) in breast cancer: Clinical utility in neoadjuvant and metastatic setting.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12584-e12584
Author(s):  
Serafin Morales Murillo ◽  
Ariadna Gasol Cudós ◽  
Joel Veas Rodriguez ◽  
Carles Canosa Morales ◽  
Jordi Melé Olivé ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Fdg Pet ◽  
Triple Negative ◽  
Residual Tumor ◽  
Her2 Status ◽  
Her2 Positive ◽  
Initial Node ◽  
Positron Emission ◽  
Metastatic Setting

e12584 Background: FDG-PET in clinical practice is based on the detection of a relapse and the initial staging but its role as a predictive factor or its correlation with biological parameters is very controversial. Methods: We analyzed the SUV of FDG-PET in a cohort with 36 patients in neoadjuvant setting and 112 with metastatic disease. Results: The median of SUV in neoadjuvant was 8,95 (range 2,8-30) with higher SUV in triple negative (11,7 range 2,8-18,8) than HER2 positive (8,75 range 4-30) and luminal patients (7,9 range 4,4-16). We don´t find a correlation between the SUV with either histological and clinical variables but there was a slightly correlation with residual tumor (p:0,068) and initial node involvement (p:0,069). In the 112 metastatic cohort the median SUV was 7,95 (range 2-28) with higher SUV in triple negative (10,1 range 3,4-19) than HER2 positive (9,7 range 4-28) and luminal patients (7,6 range 2.21). We found only a correlation between the SUV and progesterone receptor value (OR 0,875 p:0,005) but not in estrogen receptor, Ki67 index and HER2 status. In the survival analysis we don´t find a correlation between the SUV value and the disease free and overall survival included the analysis for different phenotypes. Conclusions: The SUV of the FDG-PET is very variable in all phenotypes of breast cancer being higher in the triple negative phenotype and lower in the luminal. The SUV value is very similar in neoadjuvant and metastatic setting. We only correlated the SUV value with the progesterone receptor in the metastatic cohort. We don´t find a prognostic value of the initial value of SUV in the two cohorts.

scholarly journals Estimating Breast Cancer Survival by Molecular Subtype in the Absence of Screening and Adjuvant Treatment

2018 ◽  
Vol 38 (1_suppl) ◽  
pp. 32S-43S ◽  
Author(s):  
Diego F. Munoz ◽  
Sylvia K. Plevritis
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Cancer Survival ◽  
Molecular Subtype ◽  
Breast Cancer Survival ◽  
Her2 Status ◽  
Survival Outcomes ◽  
Treatment Interventions ◽  
Molecular Subtyping ◽  
Incidence And Mortality

Background. As molecular subtyping of breast cancer influences clinical management, the evaluation of screening and adjuvant treatment interventions at the population level needs to account for molecular subtyping. Performing such analyses are challenging because molecular subtype-specific, long-term outcomes are not readily accessible; these markers were not historically recorded in tumor registries. We present a modeling approach to estimate historical survival outcomes by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. Method. Our approach leverages a simulation model of breast cancer outcomes and integrates data from two sources: the Surveillance Epidemiology and End Results (SEER) databases and the Breast Cancer Surveillance Consortium (BCSC). We not only produce ER- and HER2-specific estimates of breast cancer survival in the absence of screening and adjuvant treatment but we also estimate mean tumor volume doubling time (TVDT) and mean mammographic detection threshold by ER/HER2-status. Results. In general, we found that tumors with ER-negative and HER2-positive status are associated with more aggressive growth, have lower TVDTs, are harder to detect by mammography, and have worse survival outcomes in the absence of screening and adjuvant treatment. Our estimates have been used as inputs into model-based analyses that evaluate the effects of screening and adjuvant treatment interventions on population outcomes by ER and HER2 status developed by the Cancer Intervention and Surveillance Modeling Network (CISNET) Breast Cancer Working Group. In addition, our estimates enable a re-assessment of historical trends in breast cancer incidence and mortality in terms of contemporary molecular tumor characteristics. Conclusion. Our approach can be generalized beyond breast cancer and to more complex molecular profiles.

Functional subtyping with BluePrint 80-gene profile to identify distinct triple-positive subtypes with and without trastuzumab/chemosensitivity.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 114-114 ◽  
Author(s):  
Pat W. Whitworth ◽  
Peter D. Beitsch ◽  
Michael C. Rotkis ◽  
James V. Pellicane ◽  
Mary Murray ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Treatment Decision ◽  
Excision Biopsy ◽  
Molecular Subgroups ◽  
Luminal A ◽  
Accurate Identification ◽  
Molecular Subtyping ◽  
Luminal B ◽  
Type Group

114 Background: Classification by molecular subtype can aid in the selection of therapy for patients with breast cancer. However at present, the methodology for molecular subtyping is not standardized. The aim of the prospective NBRST study is to compare chemosensitivity as defined by pathological Complete Response (pCR) using the 80-gene BluePrint (BP) functional subtype profile vs. conventional IHC/FISH subtyping. Methods: The study includes women aged 18–90 with histologically proven breast cancer, written informed consent, no excision biopsy or axillary dissection, and no prior therapy for breast cancer. Neo-adjuvant Chemotherapy (NCT) was at the discretion of the physician adhering to NCCN approved or other peer-reviewed regimens. BP in combination with MammaPrint classifies patients into 4 molecular subgroups: Luminal A, Luminal B, HER2 and Basal. Results: 721 patients had definitive surgery. 58/335 (17%) IHC/FISH HR+/HER2- patients were re-classified by BP as Basal (57) or HER2 (1). 92/222 (41%) IHC/FISH HER2+ patients were re-classified as BP Luminal (67) or BP Basal (25). 7/164 (4%) IHC/FISH triple negative (TN) patients were re-classified as BP Luminal (5) or BP HER2 (2). NCT pCR rates were 3% in Luminal A and 9% in Luminal B patients versus 10% pCR in IHC/FISH luminal patients. The NCT pCR rate was 54% in BP HER2 patients. This is significantly superior (p = 0.02) to the pCR rate in IHC/FISH HER2+ patients (40%). BP Basal and IHC/FISH TN had a pCR rate of 35%. Functional BP subtyping divided the 137 IHC/FISH triple positive patients into two major subgroups: BP Luminal (n = 66, pCR = 11%) and BP HER2 (n = 60, pCR = 45%).11 patients were re-classified as BP Basal with pCR = 45%. Conclusions: Molecular subtyping using BP leads to a reclassification of 23% of tumors. The re-classification is most prominent in classically assessed triple positive patients where 48% of patients are re-assigned to the less responsive BP Luminal-type group vs. 44% of patients assigned to the responsive BP HER2-type group. These findings confirm the more accurate identification of molecular subgroups for treatment decision by BluePrint functional subtype classifier. Clinical trial information: NCT01479101.

scholarly journals Characteristics of HER2 FISH-Equivocal Breast Cancers and the Impacts on HER2 Status of 2018 ASCO/CAP Guideline

2021 ◽  
Author(s):  
Hui Kong ◽  
Qianming Bai ◽  
Anqi Li ◽  
Xiaoyan Zhou ◽  
Wentao Yang
Keyword(s):  
Copy Number ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Chromosome 17 ◽  
Clinicopathological Parameters ◽  
Her2 Status ◽  
Breast Cancers ◽  
Luminal A ◽  
Luminal B ◽  
The Relationship

Abstract Background: According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with HER2 IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated.Methods: 195 HER2 FISH-equivocal breast cancers were collected between 2014 and 2018. The molecular subtype was determined according to 2013 St Gallen consensus, and HER2 status was also redefined following 2018 ASCO/CAP guideline. All cases were classified into 4 groups according to the average HER2 copy number (4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed. Results: 183 (93.8%) of 195 FISH-equivocal cases were of luminal subtype, while the other 12 (6.2%) were undetermined. Using 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized to HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) cases were treated with trastuzumab, but showed no difference in prognosis with patients who didn’t receive targeted therapy.Conclusions: In this study, all HER2 FISH-equivocal breast cancers were reclassified to be HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.

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