Clinicopathological features and evaluation of microsatellite stability of colorectal carcinoma with cribriform comedo pattern.

BACKGROUND: Cribriform comedo-type adenocarcinoma (CCA) was a colon cancer subtype defined in the 2009 World Health Organization (WHO) classification. In the 2018 classification, it was a colon cancer subtype included in the adenocarcinoma, Not otherwise specified (NOS) group. A few studies have reported that colon cancers with a cribriform pattern have worse overall survival, and most of them are microsatellite stable (MSS). In this study, we evaluated CCAs based on their clinicopathologic features and microsatellite stability. We aimed to answer whether these tumors could be defined as a distinct morphologic subtype with prognostic significance. MATERIALS AND METHODS: Pathology reports and specimens from 449 patients with colorectal adenocarcinoma (CRA) were re-evaluated. All subtypes were determined. To evaluate MSS status, the CCA cases were immunohistochemically stained with anti-MLH1, MSH2, MSH6, and PMS2 antibodies. RESULTS: CCA was present in 40.5% of cases. These cases were found to have higher rates of lymph node metastasis, lymphovascular-perineural invasion, metastasis, and advanced stage ( P < 0.05). Also, 2.7% of CCA cases were microsatellite instable (MSI). However, no statistically significant result was found regarding overall survival and progression-free survival of CCA cases with MSI. CONCLUSION: According to the findings, CRAs with comedo cribriform patterns are tumors with more aggressive features. It can be said that these tumors have a specific molecular feature related to MSS. Because this feature is important for planning adjuvant chemotherapy, it may be useful to identify cases, particularly with a cribriform comedo pattern >90%. However, because no significant difference in survival rates was found, CCAs may not need to be defined as distinct subtypes.

Can daily bathing with 4% chlorhexidine + daily chlorhexidine wipe for 1 week be effective in decolonizing Candida auris colonization?

BACKGROUND: Herein, it is aimed to present the decolonizing rates of Candida auris colonized cases after daily bathing with 4% chlorhexidine plus daily cleaning with 4% chlorhexidine wipe for 1 week (will be mentioned as DCHX). METHODS: The study period was from October, 2021, to November, 2022. Inclusion criteria were (i) age > 18, (ii) receiving DCHX, (iii) proven C. auris carrier on auricular, or axillar or inguinal swab surveillance cultures up to 5-day period before DCHX. Cases with three consecutive negative surveillance cultures 3 days apart were considered to be decolonized. RESULTS: A total of 38 cases [14 female, aged 61.8 ± 15.5 years] fulfilled the inclusion criteria. Six (15.8%), 23 (60.1%), and 22 cases (57.8%) were postauricular, inguinal, and axillary culture positive, respectively. Only three cases (7.9%) were triple culture positive. Nine cases (23.7%) had three consequent negative surveillance cultures after DCHX and were considered to be decolonized. There was no significant difference in decolonization rates of concomitant only antibiotic receiving cohort vs. concomitant antifungal + antibiotic receiving cohort (5/16 vs. 2/8, p = 1) were decolonized similarly. Of the nine C. auris decolonized cases, two developed C. auris infection in 30 days follow-up after decolonization. However, 10 (34.5%) of 29 non-decolonized cases developed C. auris infection (p: 0.450) within 30 days after surveillance culture positivity. Over all cohorts, day 30 mortality was 23.7% (9/38). CONCLUSION: In conclusion, based on our observational and relatively small uncontrolled series, it appears that DCHX is not very effective in decolonizing C. auris carriers (especially in cases who are C. auris colonized in > 1 areas), although it is not completely ineffective.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. PATIENTS AND METHODS: In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. RESULTS: The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 ≥) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. CONCLUSIONS: This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. OBJECTIVE: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. RESULTS AND LIMITATIONS: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. CONCLUSIONS: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. PATIENT SUMMARY: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma.

AIMS: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. SUBJECTS AND METHODS: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. RESULTS: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. CONCLUSIONS: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies.

Prognostic role of inflammatory biomarkers in metastatic breast cancer.

PURPOSE: The effects of inflammation on the prognosis, life expectancy and several parameters such as response to treatment of breast cancer have been previously studied. The purpose of this study was to investigate the effect of inflammatory markers on prognosis in patients with metastatic breast cancer. METHODS: This study was conducted on 81 patients with metastatic breast cancer who have been followed up at the Department of Medical Oncology, Hacettepe University Institute of Oncology, between December, 2009 and March, 2014. For all studied parameters Kaplan-Meier survival estimates and p values computed by log-rank test were calculated. A p value < 0.05 was considered statistically significant. RESULTS: Median follow-up time was 26 months. There were 38 deaths due to disease progression during the follow up. The levels of serum albumin, and erythrocyte sedimentation rate (ESR) were not associated with a significant effect on overall survival (OS). Among patients with a higher serum C-reactive protein (CRP), the estimated mean survival was 84±36 months, compared to 278±113 months among patients with a normal serum CRP (p=0.032). When patients with higher and normal lactate dehydrogenase (LDH) levels were compared, their 2-year OS survival rates were 68.2 and 87.7%, respectively (p=0.034). Among patients with higher serum ferritin levels, the estimated mean survival was 29±10 months, compared to 212±113 months for normal serum ferritin (p=0.01). Among patients with higher serum beta-2 microglobulin (ß2-M), the estimated mean OS survival was 28±8 months, compared to 84±57 months for those with normal levels (p<0.01). CONCLUSION: Serum CRP, ferritin and ß2-M can be useful prognostic factors for OS in patients with metastatic breast cancer.

The lymph node ratio as an independent prognostic factor for non-metastatic node-positive breast cancer recurrence and mortality.

PURPOSE: To examine the prognostic value of lymph node ratio (LNR) in pathological nodal (pN) stage breast cancer patients. Also, to analyse additional clinical and pathologic prognostic factors and the impact of LNR among molecular subtypes. METHODS: Among a total of 3088 patients, 1004 women with non-metastatic lymph node-positive breast cancer were analysed. The patients were classified into low (≤0.20), intermediate (0.20 to 0.65) and high-risk (>0.65) LNR groups. Univariate and multivariate Cox proportional hazards regression model for disease-free survival (DFS), and overall survival (OS) were performed to evaluate the prognostic value of LNR. RESULTS: The median LNR was 0.17 (range 0.02-1.00). Of the patients, 55.7% were in low, 32.1% in intermediate, and 12.3% in high risk group. When compared with low risk group, high risk group had more often large tumor size and high grade tumor with lymphovascular invasion. The median follow-up period was 46.8 months. The 5-year breast cancer-specific OS and DFS rates for patients with low, intermediate, and high were 88%-67%, 65%-48% and 53%-24%, respectively (both plog-rank<0.0001). On multivariate analysis, pN stage and LNR were both independent predictors of survival, however, an overlapping between N1 (250 months, 95% confidence interval [CI] 88.15-413.21) and N2 (176 months, 95% CI 129.51-222.93) curves in pN staging was determined. We also observed clear prognostic separation for triple negative breast cancer with LNR survival over pN staging. CONCLUSION: The LNR predicts survival more accurately than pN staging in node-positive breast cancer patients. The use of LNR may standardize the staging and guide decisions for adjuvant treatments.

Molecular subtypes in patients with inflammatory breast cancer; a single center experience.

PURPOSE: The purpose of this study was to investigate the frequency and prognosis of inflammatory breast cancer (IBC) according to molecular subtypes. METHODS: Demographic data were examined for 78 patients diagnosed with IBC among breast cancer patients monitored in our clinic. Patients were staged according to the 2010 AJCC guidelines. Physical examination and radiographic findings classified on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) guidelines were employed in the evaluation of clinical response to systemic therapy. Subtype analysis was performed in patients with IBC and subtypes were compared. Patients were divided on the basis of metastatic or non metastatic status and survival analysis was performed on the basis of molecular subtypes. RESULTS: Distribution analysis of molecular subtypes revealed a lower incidence of luminal A and a higher incidence of both HER 2 (+) and triple negative breast cancer in IBC. Molecular subtypes had no effect on survival in the non metastatic (p=0.61) and metastatic patient group (p=0.08). CONCLUSION: This study showed that IBC frequency is higher in HER2 overexpressing and triple negative subtypes. No survival differences were noticed in relation to molecular subtypes in IBC patients.

Comparison of three different induction regimens for nasopharyngeal cancer.

BACKGROUND: The standard treatment of local advanced nasopharyngeal cancer is chemoradiotherapy. There is a lack of data concerning induction therapy. In this study we retrospectively examined patients treated with induction therapy and chemoradiotherapy. MATERIALS AND METHODS: Locally advanced nasopharyngeal cancer patients treated between 1996 and 2013 in our clinic were included in the study. Three different induction regimens were administered to our patients in different time periods. The regimen dosages were: CF regimen, cisplatin 50mg/m2 1-2 days, fluorouracil 500mg/m2 1-5 days; DC, docetaxel 75mg/m2 1 day, cisplatin 75mg/m2 1 day; and DCF, docetaxel 75mg/m2 1 day, cisplatin 75mg/m2 1 day, 5-Fu 750mg/m2 1-5 days. Most of the patients were stage III (36.4%) and stage IV (51.7%). RESULTS: Median follow-up time was 50 months (2-201 months). Three-year progression-free survival (PFS) was 79.3%, and 5-year PFS 72.4% in all patients. Three-year overall survival (OS) was 87.4% and 5-year OS 76% in all patients. In terms of induction therapies, 3-year OS was 96.5% in the DCF group, 86.6% in the DC group and 76.3% in the CF group (p=0.03). CONCLUSIONS: There was no significant differences in response rate and PFS between the three regimens. OS in the DCF group was significantly higher than in the other groups. However, this study was retrospective and limited toxicity data were available; the findings therefore need to be interpreted with care.

Which sequence best protects the heart against trastuzumab and anthracycline toxicity? An electron microscopy study in rats.

BACKGROUND/AIM: Two effective cytotoxic agents, doxorubicin and trastuzumab, are associated with potentially life-threatening cardiotoxicity. The present study was designed to investigate cardiotoxicity aggravated by the timing of administration of trastuzumab and doxorubicin in rats. MATERIALS AND METHODS: Twenty-four rats were randomly assigned to one of four groups. These received one of the following treatment drug regimens administered via intraperitoneal injection: (i) 0.9% saline control (n=6); (ii) doxorubicin (5 mg/kg) on day 1 then trastuzumab 10 mg/kg on day 15 (n=6); (iii) trastuzumab 10 mg/ kg on day 1 then doxorubicin (5 mg/kg) on day 15 (n=6) or (iv) doxorubicin (5 mg/kg) on day 1 and trastuzumab 10 mg/ kg on day 1 (n=6). On the 30th day, the hearts were processed for pathological analysis by electron microscopy. RESULTS: Electron microscopy revealed an ultrastructurally normal heart tissue in the control group. At electron microscopic examination of the tissue samples in the second and fourth group, a mild degree of dilation was observed in the peri-nuclear cisternae of some heart muscle cells. In the third group, pathological changes were detected in mitochondria. These exhibited prominent cristae, which also showed a mild degree of ultrastructural pathology in mitochondria. CONCLUSION: Based on electron microscopy findings, sequential administration of anthracycline first, followed by trastuzumab is safer in terms of cardiotoxicity, while the most toxic schedule for the rat heart was trastuzumab first, followed by anthracycline.

A review of the use of somatostatin analogs in oncology.

Somatostatin is a neuropeptide produced by paracrine cells that are located throughout the gastrointestinal tract, lung, and pancreas, and is also found in various locations of the nervous system. It exerts neural control over many physiological functions including inhibition of gastrointestinal endocrine secretion through its receptors. Potent and biologically stable analogs of somatostatin have been developed. These somatostatin analogs show different efficacy on different receptors, and receptors are varyingly concentrated in specific tissues. Antitumor and antisecretory effects of somatostatin analogs in cancer have been shown in several in vivo and in vitro studies. However, these activities have not always yielded into clinically relevant patient outcome benefit. Somatostatin analogs are of clinical benefit in treating symptoms of ectopic hormone secretion (adrenocorticotropic hormone, growth hormone-releasing hormone) in lung cancer, without inducing a significant tumor response. They have also been shown to induce a statistically significant decrease in bone pain and increase in Karnofsky performance status in patients with metastatic prostate cancer. Somatostatin analogs alone or in combination with other agents have only limited antitumoral effect in breast cancer. In gastrointestinal cancers, studies have not shown an objective tumor response to somatostatin analogs except in endocrine tumors of the liver with symptomatic and biochemical improvement. In neuroendocrine tumors of the gastrointestinal system and pancreas, very high symptomatic and biochemical response rates have been achieved with somatostatin analogs. Antiproliferative activity has been clearly shown in metastatic midgut neuroendocrine tumors.

Association between common risk factors and molecular subtypes in breast cancer patients.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer. METHODS: This cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis. RESULTS: Thousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15-1.74; p=0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01-2.25; p=0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03-2.13; p=0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83-1.88; p=0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47-0.97; p=0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53-1.04; p=0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93-5.17; p=0.04) and luminal A (OR 1.87, 95% CI 0.93-3.90, p=0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06-3.37; p=0.04 and OR 1.90 95% CI 1.00-3.61; p=0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43-0.95; p=0.02 and OR 0.50 95% CI 0.32-0.76; p=0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands. CONCLUSIONS: Reproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.