Person: KAYA, HANDAN
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KAYA
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HANDAN
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Publication Metadata only Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values(CHURCHILL LIVINGSTONE, 2014) KAYA, HANDAN; Cserni, Gabor; Voeroes, Andras; Liepniece-Karele, Inta; Bianchi, Simonetta; Vezzosi, Vania; Grabau, Dorthe; Sapino, Anna; Castellano, Isabella; Regitnig, Peter; Foschini, Maria Pia; Zolota, Vassiliki; Varga, Zsuzsanna; Figueiredo, Paulo; Decker, Thomas; Focke, Cornelia; Kulka, Janina; Kaya, Handan; Reiner-Concin, Angelika; Amendoeira, Isabel; Callagy, Grace; Caffrey, Emer; Wesseling, Jelle; Wells, CliveThe Ki67 labelling index (LI - proportion of staining cells) is widely used to reflect proliferation in breast carcinomas. Several cut-off values have been suggested to distinguish between tumours with low and high proliferative activity. The aim of the current study was to evaluate the distribution of Ki67 LIs in breast carcinomas diagnosed at different institutions by different pathologists using the method reflecting their daily practice. Pathologists using Ki67 were asked to provide data (including the LI, type of the specimen, receptor status, grade) on 100 consecutively stained cases, as well as details of their evaluation. A full dataset of 1709 carcinomas was collected from 19 departments. The median Ki67 LI was 17% for all tumours and 14% for oestrogen receptor-positive and HER2-negative carcinomas. Tumours with higher mitotic counts were associated with higher Ki67 LIs. Ki67 LIs tended to cluster around values ending with 5 or 0 both in cases where the values were obtained by counting the proportion of stained tumour cell nuclei and those where the values were obtained by estimation. On the basis of the distribution pattern described, some currently used Ki67 LI cut off values are not realistic, and it is proposed to select more realistic values ending with 0 or 5. (C) 2014 Elsevier Ltd. All rights reserved.Publication Metadata only Neonatal Nav1.5 protein expression in normal adult human tissues and breast cancer(ELSEVIER GMBH, 2017) KAYA, HANDAN; Yamaci, Rezan Fahrioglu; Fraser, Scott P.; Battaloglu, Esra; Kaya, Handan; Erguler, Kamil; Foster, Christopher S.; Djamgoz, Mustafa B. A.Expression of the neonatal splice variant of the voltage-gated sodium channel alpha-subunit (VGSC) subtype Nav1.5 (nNav1.5), encoded by the gene SCN5A, was shown earlier to be upregulated in human breast cancer (BCa), both in vitro and in vivo. Channel activity promoted BCa invasion of Matrigel (R) in vitro and metastasis in vivo. Consequently, expression of nNav1.5 has been proposed as a functional biomarker of BCa cells with metastatic potential. Here, we have determined immunohistochemically both nNav1.5 and total VGSC (tVGSC) protein expression in a range of adult human tissues. Some VGSC protein was expressed in normal colon, small intestine, stomach, prostate, bladder and breast. As expected, high levels of VGSC protein were expressed in brain, skeletal muscle and cardiac muscle. On the other hand, nNav1.5 protein was not expressed in any of the normal tissues tested except breast where a low-level of protein was present. In comparison to normal breast, nNav1.5 protein expression in BCa was consistently widespread and occurred at a significantly higher level. We also questioned whether there was any relationship between the nNav1.5 protein expression and the estrogen receptor (ER alpha) status of BCa and obtained the following results. First, all cases lacking nNav1.5 were positive for ERa. SOecond, in all ER alpha-negative tissues, nNav1.5 protein was expressed in plasma membrane. Third, however, in ER alpha-positive cases, nNav1.5 protein expression was observed in both plasma membrane and cytoplasm. In conclusion, nNav1.5 protein has a restricted expression pattern among human tissues. High level expression occurs in BCa and associates with ERa status. These results further support the proposition that nNav1.5 is a novel biomarker of metastatic BCa. (C) 2017 Elsevier GmbH. All rights reserved.Publication Metadata only Outcomes of unconventional utilization of BI-RADS category 3 assessment at opportunistic screening(SAGE PUBLICATIONS LTD, 2016) TÜRELİ, DERYA; Altas, Hilal; Tureli, Derya; Cengic, Ismet; Kucukkaya, Fikret; Aribal, Erkin; Kaya, HandanBackground An important difficulty regarding the Breast Imaging Reporting and Data System (BI-RADS) category 3 assessment is the need for extensive diagnostic workup and an additional 6-month follow-up study. Purpose To evaluate the feasibility of the BI-RADS category 3 assessments at opportunistic screening. Material and Methods Mammography charts of 9062 screening patients in a major teaching hospital situated in an urban setting of a developing country were evaluated retrospectively (1997-2010). BI-RADS category 3 patients, called for a 6-month follow-up, which comprised a single-view spot or magnification mammogram. The length of follow-up period, compliance to periodic mammographic surveillance, cancer detection rate, and negative predictive values of category 3 assessments were calculated. Results Of the screened population, 9.2% were assigned BI-RADS category 3, and 31.2% of these cases were lost to follow-up. The mean follow-up period for 606 patients was 36.9 months. The negative predictive values for 6-month, 12-month, and final control studies were 90.9%, 87.5%, and 100%, respectively. Patient compliance for 6 months, 12 months, and any control evaluations beyond 12 months was low (50.0%, 29.8%, and 47.5%, respectively). Cancer detection rate was 0.8%. Conclusion Results of the study supports the feasibility of the BI-RADS category 3 assessments at opportunistic screening without any additional diagnostic workup. The practice of category 3 assessment following screening mammograms may be a more cost-effective method for developing countries with high recall rates and low resources in eliminating the maximum risk with minimum cost within the limits of available resources.Publication Open Access Is Regression after Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer Different in Sentinel and Non-sentinel Nodes?(SPRINGER, 2018-01) KAYA, HANDAN; Cserni, Gabor; Zombori, Tamas; Andreu, Xavier; Bianchi, Simonetta; Regitnig, Peter; Amendoeira, Isabel; Balmativola, Davide; Kovacs, Aniko; Cordoba, Alicia; Reiner, Angelika; Kulka, Janina; Kaya, Handan; Liepniece-Karele, Inta; Quinn, Cecily; Kovari, BenceTumor draining sentinel lymph nodes (SLNs) are the sites of selective changes as compared to non-SLNs. They show features of tumor-reactive lymphadenopathy, including increased total number of functional blood vessels, but a relative immunosuppressed status has also been described in them. We explored the hypothesis of a selective regression or non-regression in SLNs versus non-SLNs in 142 patients with 110 estrogen receptor-positive and 32 estrogen receptor-negative tumors undergoing both SLN biopsy and axillary lymph node dissection after neoadjuvant therapy by assessing the tumoral (metastatic) and regression statuses of SLNs and non-SLNs separately. Of the 89 cases with signs of nodal regression, 22 cases (25%) were in favor of a selective non-regression in SLNs, 18 cases (20%) were supportive of a selective and more pronounced regression in the SLNs and the remaining showed equal degrees of regression or non-regression in SLNs and non-SLNs. The results indicate that there is no obvious difference in the degree of regressive histological changes shown by SLNs and NSLNs. Therefore, this phenomenon may not be a major contributor to the higher false negative rate of SLN biopsy after neoadjuvant treatment.Publication Metadata only Clinical outcome of breast cancer patients with N3a (>= 10 positive lymph nodes) disease: has it changed over years?(HUMANA PRESS INC, 2011) DANE, FAYSAL; Basaran, Gul; Devrim, Cabuk; Caglar, Hale B.; Gulluoglu, Bahadir; Kaya, Handan; Seber, Selcuk; Korkmaz, Taner; Telli, Ferhat; Kocak, Muharrem; Dane, Faysal; Yumuk, Fulden P.; Turhal, Serdar N.It has been shown that breast cancer patients with N3a (10 positive lymph nodes) had a poor prognosis. We planned to investigate the clinical outcome BC patients who presented with N3a disease and had no evidence of systemic metastasis at the time of diagnosis. We made a retrospective chart review of breast cancer patients who had a parts per thousand yen10 positive lymph nodes and received adjuvant systemic therapy in Marmara University Hospital between 1998 and 2008. We recorded clinical, pathologic and treatment characteristics of the patients and analyzed the survival outcome. We identified 73 patients with N3a disease who were treated in Marmara University Hospital between 1998 and 2008. The median age was 52. Most (75%) of the patients had invasive ductal histology, 75% had T2/T3 tumors, 36% had grade 3 tumors. The median number of metastatic lymph nodes was 15. Estrogen and progesterone receptors were both positive in 61% and both negative in 16+ tumors. Her-2/neu status was assessed in 68% of the tumors; 18% of patients had 3+ and 50% had negative scores. Six patients had triple negative tumors. All patients except one received adjuvant chemotherapy and radiotherapy. Seventy-four percent of patients received anthracycline/taxane-based chemotherapy. Fifty-nine patients received adjuvant endocrine therapy, 42% them received aromatase inhibitors. Five of the 13 Her-2 positive patients received adjuvant trastuzumab. With a median follow-up of 47 months, 5-year disease and overall survival rates were 66 and 81%, respectively. Twenty-four patients had relapsed and 14 patients died. Her-2 status and the number of lymph nodes (< 20 vs. a parts per thousand yen20) had significant impact on disease-free survival in the univariate analysis (P = 0.03 and 0.05, respectively) and Her-2 retained its significant impact on disease-free survival in the multivariate analysis (P = 0.05). The prognosis of BC patients with N3a disease has changed favorably in the past decade with the current standards of care.Publication Metadata only Multiparametric breast MRI with 3T: Effectivity of combination of contrast enhanced MRI, DWI and 1H single voxel spectroscopy in differentiation of Breast tumors(ELSEVIER IRELAND LTD, 2016) KAYA, HANDAN; Aribal, Erkin; Asadov, Ruslan; Ramazan, Abdullah; Ugurlu, Mustafa Umit; Kaya, HandanObjectives: To evaluate the diagnostic accuracy of dynamic contrast enhanced breast MRI (DCE-MRI) combined with diffusion weighted imaging (DWI) and 1H single-voxel magnetic resonance spectroscopy (1HMRS) in differentiating malignant from benign breast lesions. Methods: One hundred twenty-nine patients with 138 lesions were included in the study. Multiparametric MRI of the breast was performed with a 3T unit. A DWI is followed by DCE-MRI and 1HMRS. All lesions were biopsied within one week after MRI. Histopathologic findings were accepted as the standard of reference. Probability of malignancy was assessed according to BI-RADS for DCE-MRI. ADC values were measured for DWI and choline peaks were assessed using a semi-quantitative method in 1HMRS. Two blinded radiologists evaluated findings in consensus. Diagnostic performance of DCE-MRI, DWI and 1HMRS alone or in combination for multiparametric imaging were statistically evaluated. Results: Histopathology revealed malignancy in 54.4% of lesions (75/138). DCE-MRI showed the highest AUC (0.978), sensitivity (97.33%) and specificity (88.89%) compared to DWI and 1HMRS. Sensitivity was 100% when a positive result from any one of three techniques was accepted as malignancy, albeit with a trade-off for 65.1% specificity. Highest specificity (98.4%) was attained when all three techniques were required to be positive, though with a lower sensitivity (82.7%) as trade-off. Logistic regression analysis confirmed significant association with DCE-MRI (p < 0.001) and 1H MRS (p = 0.009) but not with DWI (p = 0.127). There was one case of fat necrosis which was false positive in all three techniques. Conclusions: Multiparametric imaging with combination of DCE-MRI, DWI and 1HMRS does not improve, and may even reduce the diagnostic accuracy of breast MRI. Although, the specificity may be improved with a trade-off for lower sensitivity, we have not set a convenient algorithm for the combined use of these techniques. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Publication Metadata only The value of MRI contrast enhancement in biopsy decision of suspicious mammographic microcalcifications: a prospective multicenter study(SPRINGER, 2021) KAYA, HANDAN; Taskin, Fusun; Kalayci, Cem Burak; Tuncbilek, Nermin; Soydemir, Efe; Kurt, Nazmi; Kaya, Handan; Aribal, ErkinObjectives To investigate the inclusion of breast MRI in radiological assessment of suspicious, isolated microcalcifications detected with mammography. Methods In this prospective, multicenter study, cases with isolated microcalcifications in screening mammography were examined with dynamic contrast-enhanced MRI (DCE-MRI) before biopsy, and contrast enhancement of the relevant calcification localization was accepted as a positive finding on MRI. Six experienced breast radiologists evaluated the images and performed the biopsies. Imaging findings and histopathological results were recorded. Sensitivity, specificity, NPV, and PPV of breast MRI were calculated and compared with histopathological findings. Results Suspicious microcalcifications, which were detected by screening mammograms of 444 women, were evaluated. Of these, 276 (62.2%) were diagnosed as benign and 168 (37.8%) as malignant. Contrast enhancement was present in microcalcification localization in 325 (73.2%) of the cases. DCE-MRI was positive in all 102 invasive carcinomas and in 58 (87.9%) of 66 DCIS cases. MRI resulted in false negatives in eight DCIS cases; one was high grade and the other seven were low-to-medium grade. The false-negative rate of DCE-MRI was 4.76%. The sensitivity, specificity, PPV, and NPV for DCE-MRI for mammography-detected suspicious microcalcifications were 95.2%, 40.2%, 49.2%, and 93.3%, respectively. Conclusions In this study, all invasive cancers and all DCIS except eight cases (12.1%) were detected with DCE-MRI. DCE-MRI can be used in the decision-making algorithm to decrease the number of biopsies in mammography-detected suspicious calcifications, with a tradeoff for overlooking a small number of DCIS cases that are of low-to-medium grade.Publication Open Access Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?(BMC, 2020-12) DANE, FAYSAL; Alan, Ozkan; Akin Telli, Tugba; Aktas, Bilge; Koca, Sinan; Okten, Ilker Nihat; Hasanov, Rahib; Basoglu, Tugba; Arikan, Rukiye; Demircan, Nazim Can; Ercelep, Ozlem; Kaya, Serap; Ugurlu, Mustafa Umit; Kaya, Handan; Akgul Babacan, Nalan; Dane, Faysal; Yumuk, Perran FuldenPurpose Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. Methods Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin x fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. Results Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2),p= 0.01]. Conclusion Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.Publication Metadata only PIK3CA and TP53 MUTATIONS and SALL4, PTEN and PIK3R1 GENE EXPRESSION LEVELS in BREAST CANCER(WALTER DE GRUYTER GMBH, 2020) KAYA, HANDAN; Dirican, Ebubekir; Seven, Ipek Erbarut; Kaya, Handan; Ugurlu, M. Umit; Peker, Irem; Gulluoglu, Bahadir M.; Ozer, Ayse; Akkiprik, MustafaObjective: A high frequency of PI3K signalling pathway abnormalities and TP53 mutations are critical in the development and progression of breast cancer (BCa). We aimed to detect PIK3CA and TP53 mutations via an expression analysis of PIK3R1, PTEN and SALL4 and correlate the expression of these genes with clinical parameters of BCa. Materials and methods: PIK3CA and TP53 mutations in BCa samples were analysed by High-Resolution Melting (HRM) analysis, followed by Sanger sequencing, and the expression levels of PIK3R1, PTEN and SALL4 were evaluated by RT-PCR methods. Results: The frequency of PIK3CA and TP53 mutations was 42% and 38% according to the HRM and Sanger sequencing. There was a significantly high frequency of these mutations in ER(+), N0 and HER2(-) tumour samples. PIK3R1 and PTEN expression levels were high in tumour samples, whereas SALL4 expression was low. In patients with TP53 mutations, PIK3R1 expression was low, and this finding was statistically significant. PIK3R1 and PTEN expression levels showed statistically significant, respectively in G3 grades, ER(+), (PR)(+), HER2(+) and ER(+). Conclusions: We suggest that these candidate genes could be potential prognostic biomarkers of BCa and that they should be considered in the evaluation of clinical parameters of BCa.Publication Open Access Prediction of nipple involvement in breast cancer after neoadjuvant chemotherapy: Should we rely on breast MRI to preserve the nipple(2023-01-01) UĞURLU, MUSTAFA ÜMİT; BUĞDAYCI, ONUR; AKMERCAN, AHMET; KAYA, HANDAN; AKOĞLU, HALDUN; GÜLLÜOĞLU, MAHMUT BAHADIR; UĞURLU M. Ü., BUĞDAYCI O., AKMERCAN A., KAYA H., AKIN TELLİ T., AKOĞLU H., GÜLLÜOĞLU M. B.Background: Indications for nipple sparing mastectomy (NSM) is extending to post-neoadjuvant chemotherapy (NAC) setting. Eligibility for NSM with an optimum tumor-nipple distance (TND) after NAC is unclear. We examined predictive factors for nipple tumor involvement in patients undergoing total mastectomy following NAC. Methods: Clinical and pathological data from prospectively collected medical records of women with invasive breast carcinoma, who were undergone NAC and total mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection were analyzed. PreNAC and postNAC magnetic resonance imaging (MRI) views were examined and a cut-off TND value for predicting the negative nipple tumor status was determined. Results: Among 180 women, the final mastectomy specimen analysis revealed that 12 (7%) had nipple involvement as invasive carcinoma. Patients with nipple involvement had more postNAC multifocal/multicentric tumors (p: 0.03), larger tumors on preNAC and postNAC images (p: 0.002 and p 2mm) on preNAC and postNAC images (p < 0.001 and p: 0.01). The best likelihood ratios (LR) belonged to the postNAC positivity of the < 20 mm TND, with a + LR of 3.40, and − LR of 0.11 for nipple involvement. PreNAC positivity of the < 20 mm TND also had a similar − LR of 0.14. Conclusion: A TND-cut-off ≥ 2 cm on preNAC and postNAC MRI was shown to be highly predictive of negative nipple tumor involvement.