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While some clinics have adopted abbreviated neoadjuvant treatment for HER2-positive breast cancer, there remains a shortage of comprehensive clinical data to support this practice. This is a retrospective, multicenter study. A total of 142 patients were included in the study who are HER2-positive breast cancer, aged ≤ 65 years, with left ventricular ejection fraction ≥ 50%, received neoadjuvant chemotherapy and underwent surgery at 10 different oncology centers in Türkiye between October 2016 and December 2022. The treatment arms were divided into 4-6 cycles of docetaxel/trastuzumab/pertuzumab for arm A, 4 cycles of adriamycin/cyclophosphamide followed by 4 cycles of taxane/TP for arm B. There were 50 patients (35.2%) in arm A and 92 patients (64.8%) in arm B. The median follow-up of all of the patients was 19.9 months (95% CI 17.5-22.3). The 3-year DFS rates for treatment arms A and B were 90.0% and 83.8%, respectively, and the survival outcomes between the groups were similar (p = 0.34). Furthermore, the pathologic complete response rates were similar in both treatment arms, at 50.0% and 51.1%, respectively (p = 0.90). This study supports shortened neoadjuvant treatment of HER2-positive breast cancer, a common practice in some clinics., (© 2024. The Author(s).)

Purpose: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings., Methods: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed., Results: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response ( p  = 0.035) and PFS ( p  = 0.024). The presence of bone-only metastasis was associated with better treatment response ( p  = 0.002), PFS ( p  < 0.001), and OS ( p  = 0.001)., Conclusion: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Objectives: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis., Results: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p less than 0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p less than 0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p greater than 0.05).  Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates.

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 untreated female 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 >10.06 fL. 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.

Purpose: The clinical value of HER4 - a cell surface receptor that belongs to the human epidermal growth factor receptor family - for predicting survival outcomes in patients with breast cancer remains controversial. Herein, we sought to investigate the prognostic significance of HER4 immunohistochemical expression with respect to progression-free survival (PFS) and overall survival (OS) in Turkish patients with metastatic breast cancer (MBC)., Methods: MBC patients (N=45; mean age=50.5±12.7 years) were consecutively enrolled between 2000 and 2006 in the Department of Oncology at the Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections. The predictive value of HER4 expression was investigated by multivariate analysis after allowance for potential confounders., Results: The mean PFS in the study participants was 11.35 months (range:1-50), whereas the median OS was 22.18 months (range:1-76). The mean PFS in patients with a HER4 immunohistochemical score of 0, 1+, 2+, and 3+ was 11.0 ± 4.8, 11.3 ± 7.7, 11.7 ± 8.1, and 10.4 ± 7.4 months, respectively (p=0.99) . The mean OS in patients with a HER4 score of 0, 1+, 2+, and 3+ was 13.3 ± 6.8, 25.6 ± 10.8, 22.9 ± 10.7, and 13.5 ± 9.9, months, respectively (p=0.44). The results of multivariate Cox regression analysis indicated that the presence of visceral metastases was the only independent prognostic factor for both OS (HR=3.01, 95% CI=1.56-3.99, p <0.01) and PFS (HR=2.91, 95% CI=1.51-3.78, p <0.01)., Conclusion: HER4 immunohistochemical expression is not an independent predictor of OS and PFS in Turkish MBC patients.

Purpose: The presence of a pronounced tumor lymphocytic infiltrate (TLI) is deemed to reflect the presence of an immunoinflammatory response against the tumor and may thus have prognostic significance. We investigated the prognostic value of TLI detected in pathological specimens collected following neoadjuvant chemotherapy (NACT) in patients with breast cancer., Methods: 100 consecutive patients with breast cancer (mean age 47.8±11.4 years) who were scheduled to undergo anthracycline-and/or taxane-containing NACT were enrolled. Specimens collected after NACT were scored with the 4-point Klintrup scoring criteria for the presence of TLI., Results: 60 patients had low-grade TLI and 40 high-grade TLI. Comparison of the patient population according to low-grade vs high-grade TLI revealed statistically significant difference both in terms of disease-free survival (DFS) (log rank-4.28, p<0.05) and overall survival (OS) (log rank=3.96, p<0.05), with high-grade TLI patients showing a better prognosis. Multivariate Cox regression analysis identified postoperative tumor size and low-grade TLI as the two main independent adverse prognostic factors., Conclusion: High-grade TLI may interfer with tumor growth and can represent a favorable prognostic factor in women with breast cancer undergoing NACT.

Purpose: To investigate whether the pretreatment neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) have any prognostic significance in patients with HER2-positive early breast cancer receiving adjuvant trastuzumab., Methods: 187 patients were retrospectively analyzed. The patients were separated into two groups according to the mean value of NLR and PLR (low NLR≤2.38, high NLR>2.38; and low PLR≤161.28, high PLR>161.28, respectively). The relationship between pretreatment NLR, PLR and clinicopathological factors was investigated. Univariate and multivariate Cox regression analyses were performed. To evaluate survival rates, the Kaplan-Meier method with log rank test were used., Results: The median duration of follow up was 26.0 months (range 6.0-84.0). In high NLR and PLR groups, the mean age was lower, tumor size was larger and the number of hormone receptor positive patients was higher. No statistically significant relationship was found between clinicopathological factors and both NLR and PLR groups. During follow up, the rate of relapse was 12.6% in the low NLR group, 16.2 % in the high NLR group, 12.6% in the low PLR group and 15.8% in the high PLR group (p=non significant). Although median disease free survival (DFS) was shorter in the high NLR than in the low NLR group, the difference was not statistically significant (p=0.45). No statistically significant difference was found between high and low PLR groups with regard to median DFS and overall survival (OS) (p=0.76, p=0.29, respectively)., Conclusion: We conclude that in HER2-positive early breast cancer patients receiving adjuvant trastuzumab with high pretreatment NLR, DFS was shorter. As for PLR, no effect either on DFS or on OS was registered. Prospective studies with larger number of patients are required in order to evaluate the prognostic effect of NLR and PLR in HER2-positive breast cancer patients.

Purpose: The impact of neoadjuvant chemotherapy (NACT) on immunohistochemical markers in breast cancer specimens remains controversial. We designed the current study to investigate the potential changes in estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67 expression before and after NACT in a cohort of Turkish patients with breast cancer., Methods: This research was designed as a prospective, observational study of 100 consecutive patients with breast cancer (mean age 47.8±11.4 years) who were scheduled to undergo anthracycline- and/or taxane-containing NACT before attempting cytoreductive surgery at the Department of Oncology of the Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded specimens., Results: Changes in immunohistochemical markers before and after NACT were only significant for HER-2 and Ki- 67. More specifically, the number of HER-2-positive specimens decreased from 21 before NACT to 8 after NACT (p<0.001). Similarly, the number of tumor samples positive for Ki-67 decreased significantly from 65 to 24 after NACT (p<0.001). Mean pre- and post-treatment tumor grades of differentiation before and after NACT were 2.56 ± 0.67 and 2.37±1.07, respectively (p<0.05). We did not find any significant associations between baseline ER, PR, HER2, and Ki-67 expression with both overall survival (OS) and disease- free survival (DFS)., Conclusion: Our study suggests that NACT reduces the expression of HER2 and Ki-67 in breast cancer specimens. The significance of NACT-induced changes in the immunohistochemical expression of HER2 and Ki-67 in patients with breast cancer should be further studied in future translational and clinical research.

Background: The aim of the present study was to evaluate clinicopathological characteristics of our early stage breast cancer patients who are epidermal growth factor receptor 2 (HER2) overexpressed/ amplified (HER2+), the efficacy of trastuzumab treatment and survival results., Materials and Methods: Patients with HER2- positive early stage breast cancer receiving adjuvant trastuzumab were investigated retrospectively. Clinicopathological features of 210 patients and treatment outcome were analysed. To evaluate survival rates, the Kaplan-Meier method was used. Univariate and multivariate analyses were conducted with the Cox regression model., Results: Mean age of the patients was 51.8, 71.9% being postmenopausal. Some 37.6% of patients were node negative, and 31% had T1 tumor size and 52.4% were positive for estrogen receptor. Of 210 patients, 89.5% completed planned 52 weeks adjuvant trastuzumab treatment. The median follow up was 27.5 months (6.0-86.0 ). Relapse free survival (RFS) was 68.0 months (95% CI: 62.1-74.0) and overall survival (OS) was 74.8 months (95% CI: 69.5-80.1). The 3 year OS for all patients was 92.0% and RFS was 79.6%. During follow up, relapse was detected at the rate of 14.3%. Trastuzumab associated cardiotoxicity was found at the rate of 3.3%. In univariate analyses, larger tumor size and grade III were significantly associated (p<0.05) with RFS. Multivariate analyses of covariates displaying p<0.05 identified grade III as an independent prognostic factor., Conclusions: In the present study, it was established that trastuzumab had a satisfactory safety profile and treatment efficacy as in other clinical studies and that among clinicopathological factors evaluated, only being grade 3 had a significant effect on RFS. The occurrence of relapse with adjuvant trastuzumab makes it necessary to identify molecular predictors, which will define this group better and help explain resistance to anti HER2 based therapies.

BRCA1/BRCA2 genes were screened in 117 patients with breast cancer by sequencing. Fourteen percent of patients tested positive for BRCA1/BRCA2 mutations. Four frame shift mutations, four pathogenic missense mutations, and 25 different sequence variations were detected. BRCA mutation positivity was significantly associated with Ki67 (p = .001). BRCA protein expressions were decreased in the patients harboring important mutations and polymorphisms (BRCA1;P508 stop, V1740G, Q1182R, Q1756P and BRCA2;V2466A) related with disease. Our findings contribute significantly to the types of germline BRCA1/BRCA2 mutations and their biological effects in Turkish women. These data could help guide the management of BRCA1/BRCA2 mutation-carrying patients when considering breast-conserving therapy.

Purpose: To determine the prognostic significance of estrogen receptor (ER), progesterone receptor (PR), HER2/neu, Ki-67, and nm23 immunohistochemical expression with respect to progression free survival (PFS) and overall survival (OS) in Turkish patients with invasive breast cancer (IBC)., Methods: Patients with IBC (n = 81; mean age = 51.9 ± 11.1 years) were prospectively enrolled at the Department of Oncology, Uludag University Medical Center, Bursa, Turkey. Immunohistochemistry was performed on formalin- fixed, paraffin-embedded tissue sections., Results: We did not find any significant association between immunohistochemical expression of ER, PR, HER2/ neu, Ki-67, and nm23 and the baseline characteristics of IBC patients. The median patient PFS was 30 months (range 22-45), and the median OS was 32 months (range 23-46). Stratification of the patient population according to nm23 immunohistochemical expression revealed a statistically significant difference in terms of both OS (p < 0.05) and DFS (p < 0.05). Multivariate Cox regression analysis indicated that tumor grade, axillary lymph node status, and nm23 immunohistochemical expression were the 3 main independent prognostic factors for PFS and OS in IBC patients., Conclusion: Reduced nm23 immunohistochemical expression is an independent negative prognostic factor for OS and PFS. Patients with negative nm23 expression may require a more intensive follow-up.

Background: Breast cancer (BC) is the one of the most common cancers in women. It is also a leading cause of death. Unfortunately, some patients initially present with distant metastases and are diagnosed with stage IV disease that is nearly always, by then, incurable. This retrospective analysis investigated the risk factors for stage IV BC that may underlie such late presentation., Materials and Methods: In all, 916 patients with BC who visited the medical oncology polyclinic of eight different centres in Turkeybetween December 2011 and January 2013 were analysed., Results: A total of 115 patients (12.6%) presented with stage IV disease. In univariate analysis; to comparing these with patients at other stages, no statistical difference was found for median diagnosis age or age at menarche (p=0.611 and p=0.820), whereas age at menopause and age at first live birth were significant (p=0.018 and p=0.003). No difference was detected in terms of accompanying diseases, use of oral contraceptives and hormone replacement therapy, smoking, alcohol consumption and the rate of family history of BC between the patients (p=0.655, p=0.389, p=0.762, p=0.813, p=0.229, p=0.737). However, screening methods were employed less often, the rate of illiteracy was higher, and the rate of other cancers was higher in patients with stage IV BC (p=0.022, p=0.022, p=0.018). No statistical difference was observed between the patients in terms of tumour histopathology, and status of oestrogen receptor, progesterone receptor, or human epidermal growth factor-2 receptor (p=0.389, p=0.326, p=0.949, p=0.326). Grade 3 tumours were more frequent in patients with stage IV disease (p<0.001). On multivariate analysis, risk factors for stage IV breast cancer at the time of presentation were found to be age at first live birth and educational level (p=0.003 and p=0.047)., Conclusions: Efforts should be made to perform mammography scans, in particular, at regular intervals through national training programs for all women, particularly those with family histories of breast and other types of cancer, and to establish early diagnosis of BC long before it proceeds to stage IV. Additionally, women's education had better be upgraded. In order to make women aware of BC, national education-programmes must be organised.

Background: Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer., Methods: We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures., Results: The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS., Conclusions: HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results.