Browsing by Author "Oktay E."
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Item The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG)(Humana Press Inc., 2014) Tanriverdi O.; Kaytan-Saglam E.; Ulger S.; Bayoglu I.V.; Turker I.; Ozturk-Topcu T.; Cokmert S.; Turhal S.; Oktay E.; Karabulut B.; Kilic D.; Kucukzeybek Y.; Oksuzoglu B.; Meydan N.; Kaya V.; Akman T.; Ibis K.; Saynak M.; Sen C.A.; Uysal-Sonmez O.; Pilancı K.N.; Demir G.; Saglam S.; Kocar M.; Menekse S.; Goksel G.; Yapar-Taskoylu B.; Yaren A.; Uyeturk U.; Avci N.; Denizli B.; Ilis-Temiz E.Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5–92), and the mean survival was 25.8 months (95 % CI 20.4–29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27–4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities. © 2014, Springer Science+Business Media New York.Item Prognostic significance of the baseline serum uric acid level in non-small cell lung cancer patients treated with first-line chemotherapy: a study of the Turkish Descriptive Oncological Researches Group(Humana Press Inc., 2014) Tanriverdi O.; Cokmert S.; Oktay E.; Pilanci K.N.; Menekse S.; Kocar M.; Sen C.A.; Avci N.; Akman T.; Ordu C.; Goksel G.; Meydan N.Non-small cell lung cancer (NSCLC) is one of the most common cancers. Most of the patients are inoperable at the time of diagnosis, and the prognosis is poor. Many prognostic factors have been identified in prior studies. However, it is not clear which factor is more useful. In this study, we investigated whether uric acid, the last breakdown product of purine metabolism in humans, has a prognostic significance in advanced NSCLC. A total of 384 NSCLC patients at stage IIIB/IV and who did not meet exclusion criteria were included in this retrospective cross-sectional study. The patients’ serum uric acid levels before first-line chemotherapy and demographic (age, gender, smoking), clinical (performance status, weight loss, disease stage, first-line treatment regimen), laboratory (hemoglobin, lactate dehydrogenase), and histologic (histologic type, tumor grade) characteristics were recorded. First, a cut-off value was determined for serum uric acid level. Then, the patients were stratified into four groups (quartiles) based on their serum uric acid levels. Descriptive statistics, univariate and multivariate analyses, and survival analyses were used. Majority of the patients were males, smokers and metastatic at time of diagnosis and had history of weight loss and adenocarcinoma upon pathological examination. The serum uric acid levels of all patients were determined as 4.9 ± 2.9 (range 1.9–11.3). The patients were stratified according to quartiles of serum uric acid concentration with cutoff values defined as <3.08 mg/dL (lowest quartile, Group 1), 3.09–5.91 mg/dL (Group 2), 5.92–7.48 mg/dL (Group 3), and >7.49 mg/dL (highest quartile, Group 4). Among the patients who had serum uric acid levels over 7.49, it was observed that those who also had squamous cell carcinoma had a greater rate of brain metastasis, a shorter time lapse until brain metastasis, and lower overall survival rate. It can be assumed that NSCLC patients who had histologically shown squamous cell carcinoma display brain metastasis and poor prognosis. It can be recommended to repeat this study with larger patient series including immunohistochemical, molecular, and wider laboratory investigations. © 2014, Springer Science+Business Media New York.Item Pretreatment serum albumin level is an independent prognostic factor in patients with stage IIIB non-small cell lung cancer: A study of the Turkish descriptive oncological researches group(Asian Pacific Organization for Cancer Prevention, 2015) Tanriverdi O.; Avci N.; Oktay E.; Kalemci S.; Pilanci K.N.; Cokmert S.; Menekse S.; Kocar M.; Sen C.A.; Akman T.; Ordu C.; Goksel G.; Meydan N.; Barutca S.Background: Several prognostic factors have been studied in NSCLC, although it is unknown which is most useful. In this study, we aimed to investigate whether pre-treatment serum albumin level has prognostic value in patients with Stage IIIB NSCLC. Materials and Methods: This cross-sectional study included a total of 204 patients with Stage IIIB NSCLC who met the inclusion criteria. Pre-treatment serum albumin levels and demographic, clinical, and histological characteristics, as well as laboratory variables were recorded. A cut-off value was defined for serum albumin level and the patients were stratified into four groups on thios basis. Results: The majority of the patients was males and smokers, with a history of weight loss, and squamous histological type of lung cancer. The mean serum albumin level was 3.2±1.7 g/dL (range, 2.11-4.36 g/dL). A cut-off value 3.11 g/dL was set and among the patients with a lower level, 68% had adenocarcinoma and 82% were smokers. The patients with low serum albumin levels had a lower response rate to e first-line chemotherapy with a shorter progression-free survival and overall survival. Multivariate analysis showed that low serum albumin level was an independent poor prognostic factor for NSCLC. Conclusions: This study results suggest that low serum albumin level is an independent poor prognostic factor in patients with Stage IIIB NSCLC, associated with reduction in the response rate to first-line therapy and survival rates.Item The mean platelet volume may predict the development of isolated bone metastases in patients with breast cancer: A retrospective study of the Young Researchers Committee of the Turkish Oncology Group (TOG)(Zerbinis Publications, 2016) Tanriverdi O.; Menekse S.; Teker F.; Oktay E.; Pilanci K.N.; Gunaldi M.; Kocar M.; Kacan T.; Bahceci A.; Avci N.; Akman T.; Cokmert S.; Yesil-Cinkir H.; Yanmaz M.T.Purpose: To determine the predictive value of the mean platelet volume (MPV) and the MPV/platelet count ratio on the development of isolated bone metastasis in patients with breast cancer. Methods: A total of 121 previously untreatedfemale patients with isolated bone metastases from breast cancer (group 1) were included in this retrospective cohort study. The patients enrolled in this study had similar age, biological subtypes, and duration of follow-up after diagnosis. Group 1 was compared with both 71 previously untreated women with breast cancer with no metastases at all (group 2) and 39 healthy women (group 3). Demographic data, laboratory tests and histological features of all of the patients in groups 1 and 2 were recorded and the study variables from each of the three groups were compared. Results: In group 1, the cut-off value (9.2 fL) for the MPV was determined and patients were stratified into 4 subgroups. The MPV was higher in group 1 than in either group 2 or group 3. Group 1 patients had a MPV of 8.8±3.1 fL (mean 5.1, range: 6.1-15.6) and the cut-off value for MPV was 9.2 fl. For patients in group 1, the MPV distribution was stratified into 4 groups as follows: group A included MPV values <6.08 fL, in group B values ranged from 6.09 to 8.46 fL, group C included values from 8.47 to 10.05 fL, and group D included patients with MPV values >10.06fL MPV and the presence of lymphovascular invasion were found to be independent risk factors for the development of isolated bone metastases. Conclusion: We concluded that MPV can be used to predict the development of isolated bone metastases.Item Role of increased mean platelet volume (MPV) and decreased MPV/platelet count ratio as poor prognostic factors in lung cancer(Blackwell Publishing Ltd, 2018) Omar M.; Tanriverdi O.; Cokmert S.; Oktay E.; Yersal O.; Pilancı K.N.; Menekse S.; Kocar M.; Sen C.A.; Ordu C.; Goksel G.; Meydan N.; Barutca S.Objectives: In this study, they investigated whether mean thrombocyte volume (MPV) and MPV/platelet count ratio have a prognostic significance in advanced NSCLC or not. Methods: A total of 496 NSCLC patients at stage IIIB/IV and did not meet exclusion criteria were included in the study. The demographic features (age, gender, smoking habit), clinical characteristics (performance status, weight loss, disease stage, first-line treatment regimen), laboratory tests (levels of hemoglobin, lactate dehydrogenase and calcium as well as MPV, MPV/platelet count ratio and counts of white blood cell, platelet), and histological features (histologic type, tumor grade) were recorded. Results: The MPV levels of all patients were determined as 10.2 {plus minus} 3.4 (range, 6.4-14.1 fL). With ROC curve analysis, the MPV/PC ratio was associated with a sensitivity of 67.8% and a specificity of 84.8% at a cutoff value of 0.47424 for presence of brain metastasis at the time of diagnosis. Univariate analysis showed that OS was significantly shorter in the group with an increased MPV level than in the other group (median OS time 6.8 months vs. 11.5 months, log-rank, P =.032). Multivariate analysis confirmed that an increased MPV level was an independent poor prognostic factor for OS (HR: 1.704, 95% CI: 1.274-3.415, P =.014). Conclusions: Unlike results of previous studies, the study showed that increased MPV was an important prognostic factor in patients with NSCLC. Hence, an increased MPV level may be used as a prognostic biomarker to estimate for poor overall survival in patients with NSCLC. © 2017 John Wiley & Sons LtdItem Programmed cell death ligand-1 expression in gastroenteropancreatic neuroendocrine tumors(Zerbinis Publications, 2019) Oktay E.; Yalcin G.D.; Ekmekci S.; Kahraman D.S.; Yalcin A.; Degirmenci M.; Dirican A.; Altin Z.; Ozdemir O.; Surmeli Z.; Diniz G.; Ayhan S.; Bulut G.; Erdogan A.; Uslu R.Purpose: Gastroenteropancreatic tumors (GEPNETs) is a heterogeneous disease with variable clinical course. While promising therapeutic options exist for other adult cancers, there are no new molecular-based treatments developed for GEPNETs. One of the main targets of cancer immunotherapy is the Programmed Cell Death Ligand-1 (PD-L1) pathway. Our purpose was to investigate the profile of PD-L1 expression in different organs of GEPNETs and compare the conventional immunohistochemistry (IHC) with the RNA expression analysis via real time polymerase chain reaction (RT-PCR) in order to determine which patients might be appropriate for immune check point-targeted therapy. Methods: A total of 59 surgically or endoscopically resected GEPNET tissues were retrospectively collected. The expression of PD-L1 and mRNA was evaluated with IHC. Results: The expression of PD-L1 was significantly associated with the high-grade classification (p=0.012). PD-L1 mRNA expression in tumor samples appeared to be higher compared to the corresponding normal tissues. In appendix, stomach and small intestine, the expression of PD-L1 mRNA was higher in the tumor tissues compared to the respective controls. In pancreas and colon, control tissues tend to have a higher PD-L1 mRNA expression compared to tumor tissues. PD-L1 mRNA expression was higher in GEP carcinomas (p=0.0031). Conclusion: RT-PCR was found to be more sensitive in detecting PD-L1 expression than conventional IHC. This study may provide an important starting point and useful background information for future research about immunotherapy for appendix, stomach and small intestine neuroendocrine carcinomas. © 2019 Zerbinis Publications. All rights reserved.Item A retrospective analysis on first-line bevacizumab, cetuximab, and panitumumab-containing regimens in patients with ras-wild metastatic colorectal cancer: A collaborative study by Turkish oncology group (tog)(Zerbinis Publications, 2019) Degirmencioglu S.; Tanriverdi O.; Menekse S.; Dogan M.; Hacioglu B.; Oktay E.; Erdem D.; Arpaci E.; Uluc B.O.; Turhal S.; Yilmaz M.; Pilanci K.N.; Sakin A.; Araz M.; Cokmert S.; Ozdemir O.; Sen E.; Nayir E.Purpose: To compare the efficacy and adverse effect profiles of the first-line treatment of patients with KRAS wild type metastatic colorectal cancer (CRC) in Turkey who were treated based on regimens including bevacizumab, cetuximab and panitumumab. Methods: This retrospective multicenter observational study involved a total of 238 patients who received chemotherapy in combination with either bevacizumab or cetuximab or panitumumab as first-line therapy for KRAS wild-type metastatic colorectal cancer. Patients with full medical records having pathological diagnosis of CRC adenocarcinoma were included in the study. The demographic, laboratory, histopathological and clinical characteristics of the patients were determined, and three groups were compared based on the study variables. Results: The mean age of the entire sample (n=238) was 58±11 years, 64% of which were male. The most frequent tumor localization was the rectum (37%) and G2 was the most common tumor grade (59.7%). About 63% of the patients had metastatic disease at diagnosis, with the most common site of metastasis being lung (14.7%) and liver (52.5%). Overall survival (OS) was 63.9%, while 1-, 3- And 5-year survival rates were 91.7, 56.6 and 36.9%, respectively. The expected mean survival was 49.1 months (95% CI, 42.9-55.3). The 1-, 3- And 5-year progression-free survival (PFS) rates following first-line treatment were 65.3, 26.1 and 5.6%, respectively, while disease free survival (DFS) in patients without metastasis at diagnosis was 68.5%. An analysis carried out disregarding which treatment the patients received (FOLFOX or FOLFIRI) revealed that a panitumumab-containing combination resulted in poorer prognosis compared to bevacizumab or cetuximab-containing combination (p<0.001). With regard to the adverse effect profile, the most common adverse effects were neuropathy and neutropenia in patients receiving FOLFOX-bevacizumab; neutropenia and perforation in patients receiving FOLFIRI-bevacizumab; rash and pustular infection in patients receiving FOLFIRI-cetuximab; and diarrhea in patients who received FOLFIRI-panitumumab combination. Conclusion: is the first multicenter study performed in Turkey evaluating the response to treatment and adverse effects in patients with KRAS wild-type metastatic colorectal cancer. © 2019 Zerbinis Publications. All Rights Reserved.Item HALP Score as a New Prognostic Index in Metastatic Renal Cell Cancer(College of Physicians and Surgeons Pakistan, 2022) Ekinci F.; Balcik O.Y.; Oktay E.; Erdogan A.P.Objective: To evaluate prognostic significance of the new index, designed by formulating hemoglobin, albumin, lymphocyte, and platelet (HALP) counts in patients with metastatic renal cell carcinoma (RCC). Study Design: Descriptive study. Place and Duration of Study: Department of Medical Oncology, Celal Bayar University, Manisa, Turkey and Adnan Menderes University, Aydin, Turkey, from January 2014 to April 2020. Methodology: Patients with metastatic RCC and sufficient follow-up data were included in the study as a retrospective cohort. HALP score was calculated as hemoglobin (g/L) × albumin (g/L) levels × lymphocyte count (/L)/platelet count (/L). The cut-off value was determined by examining the area under the ROC curve for the HALP value. The endpoints of this study included overall survival (OS) and progression-free survival (PFS). Results: The mean overall survival (OS) of the patients with low HALP score was 17.7 months (95% CI, 2.21 - 33.18), while the OS of the patients with high HALP score was 89.7 months (95% CI, 55.62 - 123.77) and reached statistical significance (p=0.001). The results of univariate (p = 0.009) and multivariate (p=0.012) analyses were statistically significant as well. Conclusion: The HALP score in metastatic RCC patients was closely related to the prognosis. Worse OS was found in patients with a low HALP score. © 2022 College of Physicians and Surgeons Pakistan. All rights reserved.Item Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy(BioMed Central Ltd, 2023) Karacin C.; Oksuzoglu B.; Demirci A.; Keskinkılıç M.; Baytemür N.K.; Yılmaz F.; Selvi O.; Erdem D.; Avşar E.; Paksoy N.; Demir N.; Göksu S.S.; Türker S.; Bayram E.; Çelebi A.; Yılmaz H.; Kuzu Ö.F.; Kahraman S.; Gökmen İ.; Sakin A.; Alkan A.; Nayır E.; Uğraklı M.; Acar Ö.; Ertürk İ.; Demir H.; Aslan F.; Sönmez Ö.; Korkmaz T.; Celayir Ö.M.; Karadağ İ.; Kayıkçıoğlu E.; Şakalar T.; Öktem İ.N.; Eren T.; Urul E.; Mocan E.E.; Kalkan Z.; Yıldırım N.; Ergün Y.; Akagündüz B.; Karakaya S.; Kut E.; Teker F.; Demirel B.Ç.; Karaboyun K.; Almuradova E.; Ünal O.Ü.; Oyman A.; Işık D.; Okutur K.; Öztosun B.; Gülbağcı B.B.; Kalender M.E.; Şahin E.; Seyyar M.; Özdemir Ö.; Selçukbiricik F.; Kanıtez M.; Dede İ.; Gümüş M.; Gökmen E.; Yaren A.; Menekşe S.; Ebinç S.; Aksoy S.; İmamoğlu G.İ.; Altınbaş M.; Çetin B.; Uluç B.O.; Er Ö.; Karadurmuş N.; Erdoğan A.P.; Artaç M.; Tanrıverdi Ö.; Çiçin İ.; Şendur M.A.N.; Oktay E.; Bayoğlu İ.V.; Paydaş S.; Aydıner A.; Salim D.K.; Geredeli Ç.; Yavuzşen T.; Doğan M.; Hacıbekiroğlu İ.Background: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). Methods: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. Results: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0–14.0) months in the ET arm of group A, and 5.3 (3.9–6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8–7.7) months in the ET arm of group B, and 5.7 (4.6–6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5–8.0) months in the ET arm of group C and 4.0 (3.5–4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. Conclusion: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET. © 2023, The Author(s).Item Correction: Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy (BMC Cancer, (2023), 23, 1, (136), 10.1186/s12885-023-10609-8)(BioMed Central Ltd, 2023) Karacin C.; Oksuzoglu B.; Demirci A.; Keskinkılıç M.; Baytemür N.K.; Yılmaz F.; Selvi O.; Erdem D.; Avşar E.; Paksoy N.; Demir N.; Göksu S.S.; Türker S.; Bayram E.; Çelebi A.; Yılmaz H.; Kuzu Ö.F.; Kahraman S.; Gökmen İ.; Sakin A.; Alkan A.; Nayır E.; Uğraklı M.; Acar Ö.; Ertürk İ.; Demir H.; Aslan F.; Sönmez Ö.; Korkmaz T.; Celayir Ö.M.; Karadağ İ.; Kayıkçıoğlu E.; Şakalar T.; Öktem İ.N.; Eren T.; Erul E.; Mocan E.E.; Kalkan Z.; Yıldırım N.; Ergün Y.; Akagündüz B.; Karakaya S.; Kut E.; Teker F.; Demirel B.Ç.; Karaboyun K.; Almuradova E.; Ünal O.Ü.; Oyman A.; Işık D.; Okutur K.; Öztosun B.; Gülbağcı B.B.; Kalender M.E.; Şahin E.; Seyyar M.; Özdemir Ö.; Selçukbiricik F.; Kanıtez M.; Dede İ.; Gümüş M.; Gökmen E.; Yaren A.; Menekşe S.; Ebinç S.; Aksoy S.; İmamoğlu G.İ.; Altınbaş M.; Çetin B.; Uluç B.O.; Er Ö.; Karadurmuş N.; Erdoğan A.P.; Artaç M.; Tanrıverdi Ö.; Çiçin İ.; Şendur M.A.N.; Oktay E.; Bayoğlu İ.V.; Paydaş S.; Aydıner A.; Salim D.K.; Geredeli Ç.; Yavuzşen T.; Doğan M.; Hacıbekiroğlu İ.Following publication of the original article [1], the authors reported an error in the author name of Enes Erul. Incorrect: Enes Urul Correct: Enes Erul, The original article [1] has been corrected. © 2023, The Author(s).Item Treatment efficacy of ribociclib or palbociclib plus letrozole in hormone receptor-positive/HER2-negative metastatic breast cancer(Newlands Press Ltd, 2023) Kahraman S.; Erul E.; Seyyar M.; Gumusay O.; Bayram E.; Demirel B.C.; Acar O.; Aksoy S.; Baytemur N.K.; Sahin E.; Cabuk D.; Basaran G.; Paydas S.; Yaren A.; Guven D.C.; Erdogan A.P.; Demirci U.; Yasar A.; Bayoglu İ.V.; Hizal M.; Gulbagci B.; Paksoy N.; Davarci S.E.; Yilmaz F.; Dogan O.; Orhan S.O.; Kayikcioglu E.; Aytac A.; Keskinkilic M.; Mocan E.E.; Unal O.U.; Aydin E.; Yucel H.; Isik D.; Eren O.; Uluc B.O.; Ozcelik M.; Hacibekiroglu I.; Aydiner A.; Demir H.; Oksuzoglu B.; Cilbir E.; Cubukcu E.; Cetin B.; Oktay E.; Erol C.; Okutur S.K.; Yildirim N.; Alkan A.; Selcukbiricik F.; Aksoy A.; Karakas Y.; Ozkanli G.; Duman B.B.; Aydin D.; Dulgar O.; Er M.M.; Teker F.; Yavuzsen T.; Aykan M.B.; Inal A.; Iriagac Y.; Kalkan N.O.; Keser M.; Sakalar T.; Menekse S.; Kut E.; Bilgin B.; Karaoglanoglu M.; Sunar V.; Ozdemir O.; Turhal N.S.; Karadurmus N.; Yalcin B.; Nahit Sendur M.A.Background: Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods: The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole. Results & conclusion: The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference. © 2023 Future Medicine Ltd.