HER2 status of patients with invasive breast cancer in a population at a single UK centre: Correlation with tumor characteristics

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11094-11094
Author(s):  
B. Saleh ◽  
S. Jader ◽  
J. Singer ◽  
S. Jenkins ◽  
H. Bradpiece ◽  
...  

11094 Background: The human epidermal growth factor receptor 2 (HER2) overexpression, has been correlated with higher histological grade, increased tumour size, positive lymph node status, and negative or lower oestrogen receptor (ER) expression. Our aim was to look at the association between HER2 status, patient age and tumour histopathologic characteristics. Methods: We analysed retrospectively 735 cases of invasive breast cancer treated between the years 2000 and 2004. HER2 was measured by immunohistochemistry (IHC) and all IHC 2+ tumours were also tested by fluorescent in situ hybridisation (FISH). All information was collected from pathology reports in patient case records. Results: A total of 143 (19.5%) tumours were HER2 positive (120 IHC 3+ and 23 IHC 2+/FISH+). Of the 66 tumours that were IHC 2+, 23 (34.8%) were FISH-positive. The age of most patients (75.8%) was over 50 years but there was a higher incidence (28%) of HER2 overexpresion in the 40–49 age group compared to all other age groups, the incidence of HER2 overexpression was still at least 17–18% in all age groups, including patients aged =70 years. Although, a high proportion of patients (62.2%) had tumours less than 2 cm in size, comparison of tumours less than 2 cm with those greater than 2 cm showed no predictive effect of size on HER2 expression. Over half of the patients had lymph node-negative disease (55.2%) and despite some association of HER2 expression with lymph node involvement (odds ratio of 1.23 for comparison of lymph node-positive versus negative), 19% of lymph node-negative tumours overexpressed HER2. Most tumours were high grade (32.8% grade 3, 44.1% grade 2 ) and although the proportion of HER2 overexpression increased with increasing tumour grade, some grade 1 tumours still overexpressed HER2. A higher proportion (28%) of ER-negative tumours was HER2 positive compared to ER-positive tumours (18%); however, co-expression of HER2 and ER occurred in 14% (105/735) of all primary cancers. Conclusions: In conclusion, it is not possible to predict which patients will be HER2 positive. Therefore, it is essential that HER2 status should be determined in all patients with invasive breast cancer to allow a decision on the use of trastuzumab and guide the choice of chemotherapy. No significant financial relationships to disclose.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11043-11043 ◽  
Author(s):  
Julia Katharina Neugebauer ◽  
Brigitte Kathrin Rack ◽  
Bernadette Anna Sophia Jaeger ◽  
Ulrich Andergassen ◽  
Aurelia Pestka ◽  
...  

11043 Background: The discordance between HER2-expression on circulating tumor cells (CTC) in peripheral blood and the primary tumor has already been shown by our study group for early breast cancer patients with HER2-positive tumors. Here, we compare the results to CTC prevalence and HER2-status of CTC after adjuvant chemotherapy. Methods: The SUCCESS B trial compares FEC-Docetaxel vs. FEC-Docetaxel-Gemcitabine and HER2-targeted therapy as adjuvant treatment for patients with early, HER2-positive, node positive or high risk node negative primary breast cancer. We prospectively analyzed 23ml peripheral blood before and after chemotherapy. CTC and HER2-status were assessed with the CellSearchSystem (Veridex, USA). After immunomagnetic enrichment with an anti-Epcam-antibody, cells were labeled with anti-CK 8/18/19, anti-CD45 antibodies as well as a fluorescein conjugate antibody for HER2-phenotyping. Cutoff for CTC positivity was ≥ 1 CTC. HER-positivity of CTC was assigned if at least one CTC showed strong HER2 staining (3+). Results: CTCs and their HER2-status both before and after chemotherapy were available for 392 patients. In 179 (45.7%) patients no CTC were detected before and after chemotherapy. CTC status changed from positive before to negative after chemotherapy in 104 (26.5%) patients and from negative before to positive after chemotherapy in 69 (17.6%) patients, while 40 (10.2%) patients had a consistently positive CTC status. Patients were significantly more likely to change their CTC status from positive to negative than from negative to positive (p = 0.01). Of the 40 patients with CTC both before and after chemotherapy, 14 (35%) patients had HER2-positive CTC before and after therapy, and 9 (22%) patients had HER2-negative CTC at both time points. 7 (18%) patients had HER2-positive CTC before but not after chemotherapy, while 10 (25%) patients showed the reverse pattern (p = 0.63). Conclusions: Cytotoxic treatment does not seem to influence the HER2-status on CTC. Follow-up data within the Success B trial will analyze the relevance of the HER2-expression of CTC to predict the efficacy of targeted treatment.


2018 ◽  
Vol 11 (1) ◽  
pp. 177-191
Author(s):  
Nada A.S. Alwan ◽  
David Kerr ◽  
Dhafir Al-Okati ◽  
Fransesco Pezella ◽  
Furat N. Tawfeeq

Background:Breast cancer is the most common cancer in Iraq and the United Kingdom. While the disease is frequently diagnosed among middle-aged Iraqi women at advanced stages accounting for the second cause of cancer-related deaths, breast cancer often affects elderly British women yielding the highest survival of all registered malignancies in the UK.Objective:To compare the clinical and pathological profiles of breast cancer among Iraqi and British women; correlating age at diagnosis with the tumor characteristics, receptor-defined biomarkers and phenotype patterns.Methods:This comparative retrospective study included the clinical and pathological characteristics of (1,940) consecutive female patients who were diagnosed with invasive breast cancer from 2014 to 2016 in Iraq (Medical City Teaching Hospital, Baghdad: 635 cases) and UK (John Radcliffe, Oxford and Queen's, BHR University Hospitals: 1,305 cases). The studied parameters in both groups comprised the age of the patient at the time of diagnosis, breast cancer histologic type, grade, tumor size, lymph node status, clinical stage at presentation, Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 positive tumor contents and the receptor-defined breast cancer surrogate subtypes.Results:The Iraqi patients were significantly younger than their British counterparts and exhibited higher trend to present at advanced stages; reflected by larger size tumors and frequent lymph node involvement compared to the British (p<0.00001). They also had worse receptor-defined breast cancer subtypes manifested by higher rates of hormone receptor (ER/PR) negative, HER2 positive tumor contents, Triple Positive and Triple Negative phenotypes (p<0.00001). Excluding HER2 status, the significant differences in the clinical and tumor characteristics between the two populations persisted after adjusting for age among patients younger than 50 years.Conclusion:The remarkable differences in the clinical and tumor characteristics of breast cancer between the Iraqi and British patients suggest heterogeneity in the underlying biology of the tumor which is exacerbated in Iraq by the dilemma of delayed diagnosis. The significant ethnic disparities in breast cancer profiles recommend the prompt strengthening of the national cancer control plan in Iraq as a principal approach to the management of the disease.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6599-6599
Author(s):  
Andrew Cota Shaw ◽  
Hanna Kelly Sanoff ◽  
Mark E Smolkin

6599 Background: Many cancer centers routinely re-review outside pathologic specimens. We hypothesized re-review rarely changes patient treatment plans. Methods: Of 1495 patients seen at the University of Virginia with a diagnosis of breast cancer from 2006-2011, the 276 cases with both internal and outside pathology reports comprised the study cohort. Interobserver agreement (kappa coefficient, K) between internal and outside diagnoses were calculated for histopathology, lymph node, margin, ER/PR, and HER2 status. We then evaluated if the change would result in a change in therapy or surveillance per the National Comprehensive Cancer Network (NCCN) guidelines. The effect of region and teaching affiliation of outside institutions was explored. Results: For the 276 cases with re-reviewed pathology at UVA there was absolute agreement for ER/PR and surgical margins, and excellent agreement for lymph node, K= 0.93, and histopathology, K=0.93. Agreement was good for HER2, K=0.83. 3 cases were changed from HER2 positive to negative (2) or intermediate (1). Of 9 changes in histopathology, 2 had a major upgrade: 1 ADH to DCIS; 1 DCIS to carcinoma. 3 had a major downgrade: 2 from DCIS to ADH; 1 from carcinoma to DCIS. 2 cases changed from ALH to LCIS. Lymph node status was changed from positive to negative in one out of 31 reviewed cases. Treatment plan would have changed for all 13, 4.7% of all patients. Changes were made almost exclusively (11/13) if referred from a hospital with no or minor teaching affiliation, including all major histopathology changes and changes in lymph node and HER2 status. Conclusions: Interobserver agreement for breast pathology between pathologists at an NCI designated cancer center and outside institutions was good. However, 4.7% of women had discordant results that would lead to a change in their care. Changes were most common for noninvasive carcinoma and benign atypia. In order to best utilize resources, referral centers may want to consider limiting re-review to the pathology from centers with high risk for discordance.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12019-e12019
Author(s):  
Gang Nie ◽  
Haibo Wang ◽  
Yuhua Song ◽  
Yan Mao ◽  
Weihong Cao ◽  
...  

e12019 Background: Age of patients play a key role in outcome of breast cancer, and therefore influences choice of treatment. In most studies, "young" is defined as being below 40 or 35 years. However, there are conflicts concerning definition of younger and older patients. In this study, we aim to establish a more appropriate age cut-off between “younger” and “older” breast cancer patients. Methods: A total of 5984 female breast cancer patients recruited in the Breast Cancer Registry of the Affiliated Hospital of Qingdao University during 2008 to 2014 were enrolled. Patients were divided into 11 groups by every 5 years’ age difference. The clinical characteristics and overall survival (OS) were compared among these age groups. Results: Among the five groups under age 45 (n = 1771, 30.0%), larger proportion of patients underwent breast conservation surgery in the “30-34” group (p = .027), and more patients were found with family history in the “25-29” group than in other groups (p = .029). No significant difference was found in OS (p = .059), clinicopathological stage, lymph node status, ER/PR status, HER2 status, or Ki-67 status among those five groups. For patients above 45 (n = 4813, 70.0%), differences were found in OS (p = .001) and significant differences with clinicopathological features (lymph node status, ER/PR status, HER2 status and Ki-67 status) were shown between younger and the older age groups (p = .001) among the six groups, except for family history (p = .066). Conclusions: Clinicopathological characteristics and survival status are similar among breast cancer patients under 45 years and vitiate among older patients. Age 45 is an appropriate cut-off for clinical grouping of breast cancer patients by age .


Breast Care ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. 406-410 ◽  
Author(s):  
Nina Fokter Dovnik ◽  
Andraž Dovnik ◽  
Nina Čas Sikošek ◽  
Maja Ravnik ◽  
Darja Arko ◽  
...  

Background: The natural course of traditionally prognostically unfavorable human epidermal growth factor receptor 2 (HER2)-positive breast cancer has been changed by anti-HER2 therapy. It is not clear whether the prognosis for HER2-positive patients treated with adjuvant trastuzumab differs from that of HER2-negative patients. Methods: We performed a retrospective study including patients with lymph node-negative invasive breast cancer treated at our institution in the period 2000-2009. Disease-free (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The Cox proportional hazards model was applied to control for other clinically important variables. Results: Median follow-up was 90-109 months. The 5-year DFS rates for HER2-negative patients, HER2-positive patients without adjuvant trastuzumab and trastuzumab-treated HER2-positive patients were 88.1% (95% confidence interval (CI) 85.6-90.6%), 73.1% (95% CI 64.3-81.9%) and 90.7% (95% CI 83.1-98.3%), respectively. No significant difference in DFS was observed between trastuzumab-treated HER2-positive patients and HER2-negative patients in multivariate analysis (hazard ratio 1.15; 95% CI 0.53-2.46; p = 0.728). There were no differences in OS among the 3 groups. Conclusion: Based on our results, the negative prognostic effect of HER2 positivity seen before targeted anti-HER2 treatment has completely disappeared in the era of routine trastuzumab administration in the adjuvant setting.


2009 ◽  
Vol 121 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Einar Gudlaugsson ◽  
Ivar Skaland ◽  
Emiel A. M. Janssen ◽  
Paul J. van Diest ◽  
Feja J. Voorhorst ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tatiana S. Kalinina ◽  
Vladislav V. Kononchuk ◽  
Alisa K. Yakovleva ◽  
Efim Y. Alekseenok ◽  
Sergey V. Sidorov ◽  
...  

Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs’ expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases. Thus, to identify novel metastatic markers, we evaluated the expression levels of AR; miR-185 and miR-205, both of which have been confirmed to target AR; and miR-21, transcription of which is regulated by AR, in breast cancer samples (n=89). Here, we show that the molecular subtypes of breast cancer differ in the expression profiles of AR and AR-associated microRNAs. In addition, the expression of AR and these microRNAs may depend on the expression of PR, ER, and HER2 receptors. Our results show that the possibility of using AR and microRNAs as markers depends on the tumor subtype: a decrease in AR expression may be the marker for the presence of lymph node metastases in patients with HER2-positive subtypes of breast cancer, and disturbance of miR-205, miR-185, and miR-21 expressions may be the marker in patients with a luminal B HER2-positive subtype. Cases with metastases in this type of breast cancer are characterized by a higher level of miR-205 and a lower level of miR-185 and miR-21 in tumor tissues compared to nonmetastatic cases. A decrease in the miR-185 level is also associated with lymph node metastasis in luminal B HER2-negative breast cancer. Thus, the expression levels of AR, miR-185, miR-205, and miR-21 can serve as markers to predict cancer spread to the lymph node in luminal B- and HER2-positive subtypes of breast cancer.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3057-3057
Author(s):  
P. J. Perik ◽  
M. N. Lub-De Hooge ◽  
P. L. Jager ◽  
M. A. De Korte ◽  
J. A. Gietema ◽  
...  

3057 Background: The monoclonal antibody trastuzumab, apart from antitumor effect, can induce cardiotoxicity, particularly when combined with anthracyclines. Myocardial HER2 upregulation may serve, transiently, as a compensatory mechanism induced by cardiac stress. Previously we showed in a xenograft model that 111In-DTPA-trastuzumab scintigraphy can detect HER2 positive lesions (Br J Pharmacol 2004;143:99–106) but that myocardial 111In-DTPA-trastuzumab uptake was found in only 1 of 17 anthracycline-pretreated HER2-positive metastatic breast cancer patients (ESMO 2004#50). This low number may be related to the long interval between anthracycline administration (median 11 months) and performed scan in these patients. To evaluate whether myocardial HER2 expression is induced by anthracyclines, we performed 111In-DTPA-trastuzumab scans in patients shortly after anthracycline treatment. Methods: Patients who completed 4–6 cycles of anthracycline-based chemotherapy (< 3 weeks after last dose) underwent gammacamera imaging 48 and 96 h after iv administration of 150 MBq 111In-DTPA-trastuzumab (5mg). Results: 10 anthracycline-treated patients, 8 as adjuvant breast cancer treatment and 2 for metastatic sarcoma have been enrolled. Myocardial 111In-DTPA-trastuzumab uptake was observed in 5/10 anthracycline-treated patients who all were without symptomatic cardiac dysfunction. Conclusions: Shortly after completion of anthracycline treatment myocardial HER2 overexpression was detectable in 50% of the patients. This may be a transient phenomenon. 111In-DTPA-trastuzumab scan after anthracycline treatment prior to adjuvant trastuzumab may identify patients more susceptible for trastuzumab-induced cardiotoxicity. This important observation may add to optimal timing of trastuzumab therapy i.e. when HER2/neu expression in the heart is negative (again). [Table: see text]


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 6-6
Author(s):  
G. Von Minckwitz ◽  
S. Darb-Esfahani ◽  
S. Loibl ◽  
J. B. Huober ◽  
H. Tesch ◽  
...  

6 Background: Adjacent ductal carcinoma in situ (DCIS) is in found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Methods: Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Results: Fifty nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (p=0.033). Presence of adjacent DCIS was an independent negative predictor of pCR (odds ratio 0.42 [95% CI 0.2-0.9], p=0.027). Adjacent DCIS area decreased from pre-treatment to surgery (r=0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r=0.892) and after treatment (r=0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (p=0.055). Conclusions: HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11503-e11503
Author(s):  
Kazufumi Hisamatsu

e11503 Background: In breast cancer patients, diagnosis of Axillar lymph node (Ax LN) status is practical use in deciding treatment strategy. But, diagnostic methods are different by different institution. The purpose of this study was to review diagnostic methods of Ax LN status. Methods: From December 2006, 483 cases were underwent breast cancer operation and within 356 (74%) clinical node negative primary breast cancer cases underwent Sentinel Node biopsy (SNB) by indocyanine green (ICG) fluorescence imaging. Dye was injected sub dermal in the areola. After one minute massage, subcutaneous lymphatic channel draining from the areola to the axilla was observed by Image processing and measuring system (PDE C9830, Hamamatsu Photonics Co). Skin incision was done at the point which fluorescence imaging disappeared (ASCO2011, Electronic Publication only). From September 2010, Aspiration Biopsy Cytology (ABC) of Ax LN (LN-ABC), Ultrasonography (US) and CT were done as routine workup in breast cancer patients. Node positive cases were received pre-operative chemotherapy or Ax LN dissection and node negative cases were underwent SNB by ICG fluorescence imaging during operation. Results: From December 2006, SNB were done 356 clinical node negative primary breast cancer cases. SN was detected 342 cases, detective rate was 96 %. This rate was as good as SNB done by radioactive colloid (Phytate radiolabelled by Tc98) with dye (detective rate was 95%, ASCO2011). The lymph node metastasis was detected 48 cases (14%). From Sep 2010 to Oct 2011, LN-ABC was done 49 cases of the 142 primary breast cancer patients. Fourteen cases were LN-ABC positive and 35cases were LN-ABC negative. Positive SNB were detected 3 of the 35 cases (2 cases had micro metastasis and one case had macro metastasis). Within three SNB positive cases, pre-operative US and CT had no positive finding. Positive LN-ABC cases (14 cases) were received pre-operative therapy or Ax LN dissection. Conclusions: These results suggest that LN-ABC was useful procedure detecting positive Ax LN and SNB by ICG fluorescence imaging was useful and easy tool in operative breast cancer patients.


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