Discordance between core needle biopsy (CNB) and excisional biopsy (EB) for estrogen receptor (ER), progesterone receptor (PgR) and HER2 status in early breast cancer (EBC)
ABSTRACT Analysis of estrogen receptor (ER), progesterone receptor (PgR) and HER2 status in early breast cancer (EBC) is increasingly being conducted in core needle biopsies (CNBs) taken at diagnosis but the concordance with the excisional biopsy (EB) is poorly documented.
Patients with EBC presenting to The Royal Marsden Hospital from June 2005 to September 2007 who had CNB and subsequent EB were included. ER and PgR were determined by immunohistochemistry (IHC) and graded from 0 to 8 (Allred score). HER2 was determined by IHC and scored from 0 to 3+. FISH analysis was carried out in HER2 2+ cases and in discordant cases.
In all, 336 pairs of samples were compared. ER was positive in 253 CNBs (75%) for 255 EBs (76%) and was discordant in six patients (1.8%). PgR was positive in 221 CNBs (66%) and 227 (67.6%) EBs being discordant in 52 cases (15%). HER2 was positive in 41 (12.4%) of the 331 CNBs in which it was determined compared with 44 (13.3%) EBs and discordant in four cases (1.2%).
CNB can be used with confidence for ER and HER2 determination. For PgR, due to a substantial discordance between CNB and EB, results from CNB should be used with caution.
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ABSTRACT: The insulin-like growth factor 1 receptor (IGF-1R) may be involved in the development of resistance against conventional cancer treatment. The aim of this study was to assess whether IGF-1R expression of breast tumors changes during neoadjuvant therapy and to study whether these changes were associated with survival. Paraffin embedded tumor tissue was collected from pretreatment biopsies and surgical resections of 62 breast cancer patients who were treated with neoadjuvant chemotherapy or endocrine therapy. IGF-1R expression was determined immunohistochemically and compared before and after treatment. High membranous IGF-1R expression at diagnosis correlated significantly with ER positivity, low tumor stage (stage I/II) and longer overall survival (p < 0.05). After neoadjuvant treatment, membranous IGF-1R expression remained the same in 41 (65%) tumors, was upregulated in 11 (18%) tumors and downregulated in 11 (18%) tumors. Changes in membranous IGF-1R expression were associated with overall survival (log-rank test: p = 0.013, multivariate cox-regression: p = 0.086). Mean overall survival time for upregulation, no change, and downregulation in IGF-1R expression was 3.0 ± 0.5 years, 7.3 ± 1.0 years and 15.0 ± 1.8 years, respectively. Changes in other parameters were not significantly associated with survival. Neoadjuvant therapy can induce changes in IGF-1R expression. Upregulation of IGF-1R expression after neoadjuvant treatment is a poor prognostic factor in breast cancer patients, providing a rationale for incorporating anti-IGF-1R drugs in the management of these patients.PLoS ONE 02/2015; 10(2):e0117745. DOI:10.1371/journal.pone.0117745 · 3.53 Impact Factor
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ABSTRACT: Purpose: To investigate whether longitudinal functional PET imaging of mammary tumors using the radiopharmaceuticals [18F]FDG (to measure glucose uptake), [18F]FES (to measure estrogen receptor (ER) levels), or [18F]FFNP (to measure progesterone receptor (PgR) levels) is predictive of response to estrogen deprivation therapy. Experimental Design: [18F]FDG, [18F]FES and [18F]FFNP uptake in endocrine-sensitive and -resistant mammary tumors was quantified serially by PET before ovariectomy or estrogen withdrawal in mice, and on days 3 and 4 after estrogen deprivation therapy. Specificity of [18F]FFNP uptake in ERα+ mammary tumors was determined by competition assay using unlabeled ligands for PgR or glucocorticoid receptor (GR). PgR expression was also assayed by immunohistochemistry (IHC). Results: The levels of [18F]FES and [18F]FDG tumor uptake remained unchanged in endocrine-sensitive tumors after estrogen deprivation therapy compared to those at pre-treatment. In contrast, estrogen deprivation therapy led to a reduction in PgR expression and [18F]FFNP uptake in endocrine-sensitive tumors, but not in endocrine-resistant tumors, as early as 3 days post-treatment; the changes in PgR levels were confirmed by IHC. Unlabeled PgR ligand R5020 but not GR ligand dexamethasone blocked [18F]FFNP tumor uptake, indicating that [18F]FFNP bound specifically to PgR. Therefore, a reduction in FFNP tumor to muscle ratio in mammary tumors predicts sensitivity to estrogen deprivation therapy. Conclusions: Monitoring the acute changes in ERα activity by measuring [18F]FFNP uptake in mammary tumors predicts tumor response to estrogen deprivation therapy. Longitudinal noninvasive PET imaging using [18F]FFNP is a robust and effective approach to predict tumor responsiveness to endocrine treatment. Copyright © 2014, American Association for Cancer Research.Clinical Cancer Research 12/2014; 21(5). DOI:10.1158/1078-0432.CCR-14-1715 · 8.19 Impact Factor
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ABSTRACT: Background and aim: Core needle biopsies (CNB) are now routinely performed for the clinical approach of patients with suspected breast cancer (BC). We explored the degree of concordance between CNB and surgical excised specimens (SES) regarding histological type, grade and immunohistochemistry (IHC) status. Patients and methods: We included 162 patients who underwent CNB before surgical resection. Immunohistochemistry for ER, PR, HER2 and Ki-67 was performed. Kappa test was used to obtain the concordance rate between CNB and SES regarding their histological type, grade and IHC profile. Sensitivity, specificity, PPV and NPV were calculated for CNB, considering SES as gold standard. Results: The concordance rate for histological type was 82.76% (κ = 0.49; p < 0.00). The general agreement for ER was 87.3% (κ = 0.71; p < 0.00). Nine cases were positive to PR in CNB and negative in SES, while the opposite occurred in 15 cases. We detected the highest concordance rate for HER2 expression (91.6%, κ = 0.74; p < 0.00). The calculated NPV was 98.5% for HER2 expression. Conclusions: We demonstrate that a CNB is a reliable tool for the diagnostic work-up of BC patients. A HER2 negative result should be reassuring for the clinician; however every hormone receptor negative in CNB should be regularly re-tested.