Zeljko Kovac

Factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen — Results from a prospective, single center, case control study

BACKGROUND Estimates of the risk ratio of tamoxifen-associated venous thromboembolism (VTE) in breast cancer patients range from 2.4 to 7.1. The occurrence of thrombosis in patients with breast cancer complicates the clinical condition and causes a change of treatment. Our study was conducted in order to investigate the influence of patient-related risk factors for thrombosis development in breast cancer patients whose treatment included adjuvant tamoxifen. METHODS The prospective, single center, case control study included 150 breast cancer women, 50 whom developed venous thrombosis during adjuvant tamoxifen and 100 whom did not have thrombosis, as a control group. Patient-related risk factors such as: age, body mass index, previous VTE, varicose veins, concomitant diseases, the presence of prothrombotic mutations (FV Leiden, FII G20210A) and FVIII activity were evaluated in both groups. RESULTS In respect of prothrombotic mutations, the FV Leiden mutation was present in a higher number of women from the VTE group (10/50 vs 7/100; P=0.020). Additionally, FVIII activity was significantly higher in the VTE group; median (IQR), of 1.79 (0.69) vs 1.45 (0.55); P<0.001 and more women in this group (24/50 vs 34/100) had increased FVIII activity; P=0.020. In those women with FVIII>1.5IU/ml, who were carriers of prothrombotic mutations, an OR of 3.76 (CI 95% 1.276-11.096; P=0.016) was obtained for VTE. CONCLUSION The results of our study showed that the factor V Leiden mutation and high FVIII are associated with an increased risk of VTE in women with breast cancer during adjuvant tamoxifen.

The oncology treatment of patients who use oral anticoagulants is connected with high risk of bleeding complications

The data about risk for bleeding complications during anticoagulation in cancer patients with different oncology treatment are conflicting. To investigate the rate of bleeding in the course of oral anticoagulants, during treatment of malignant diseases, we conducted a retrospective study including 75 patients on stable anticoagulation prior to commencing their different oncology treatment. All patients were treated according to the consiliar decision, made based on the localization and pathohistological findings of the malignant disease. During their treatment the regular laboratory monitoring of INR was done. Every dose of oral anticoagulants, INR changes, as well as the size and localization of bleeding were recorded. During all the malignancy treatment 22 (30%) of patients were overanticoagulated. In 15 (20%) patients it was associated with bleeding, while 3 (4%) of them had to be transfused with fresh frozen plasma to stop the major bleeding. Most bleeding complications occurred in the group of patients treated with chemotherapy or with analgesics in the group with advanced disease. None of the bleeding complications were observed in patients treated with irradiation and surgery alone, where the bridging of oral anticoagulants with low molecular weight heparin was done before surgery. The oncology treatment of patients who take oral anticoagulants was connected with high risk for bleeding especially if chemotherapy as a therapeutic options was used. Therefore physicians should be aware of this risk and carefully monitor the intensity of anticoagulant therapy, especially during the first treatment weeks when the risk of bleeding is greatest.

Long-term Survival after Cerebellar Metastasis Resection from Her2 3+ Locally Advanced Breast Cancer

We present a patient who first developed a distant metastatic site in the cerebellum during treatment for Her2 3+ locally advanced breast cancer (LABC). LABC was in complete remission at that time and isolated cerebellar metastasis was resected. The patient is still alive more than 135 months after LABC diagnosis, and more than 99 months after neurosurgery, and is still receiving trastuzumab without further progression or any toxicity. To the best of our knowledge, this is first report of such exceptional disease course for a patient with a predicted grave prognosis according to all prognostic parameters.

The risk for brain metastases in HER2 3+ BC five years after primary BC diagnosis.

e11091 Background: More than 30% of HER2 3+ BC develops brain metastases (BM) eventually, usually in the first 2-3 years after BC diagnosis. Risk for distant metastases in HER2 3+ BC remains for many years, but there are no data regarding the long term risk for BM The aim of this analysis is to is to explore whether risk for late BM, defined as BM relapse after 5 years of diagnosis) differs between patients with HER2 3+ and HER2- BC. METHODS Between January 2007-January 2011, 133 consecutive BC BM pts were identified. Patients were evaluated for age, ER/PGR/HER2 status, time to BM and BM as first relapse site according to HER2 status. BM as a first relapse site also includes BM diagnosed within 2 months after metastases in other organs developed. RESULTS Median age was 49 years (range 25-79); HER2 status (HercepTest, Dako) was known for 118 pts (88.7%) and they are considered for this analysis. HER 2 3+ was confirmed in 40 (34 %), HER2 0-2+ (2+ confirmed by CISH) in 78 (66%) and triple negative status in 19 (16 %) pts. Median time to BM in HER2 negative pts was 36 months (range 0-252).Median time to BM in HER2 3+ BC was 25 months (range 0-96); 39/40 (97,5%) HER2 3+ pts developed BM within 0-60 months, and only 1 MBC pt developed BM 96 months after BC diagnosis. That unique MBC patient, treated with trastuzumab for 8 years developed infra-tentorial BM as a terminal event. CONCLUSIONS There is a striking difference in late BM development between HER2 3+ and HER2 negative BC. For some reason, HER2 3+ BC does not or extremely rarely metastasize to the brain 5 yrs after BC diagnosis, even if metastases in the other organ sites are present. It seems that if HER2 3+ pt survive > 5 yrs without metastases, BM development is highly unlikely. Risk for BM in HER2 negative pts is retained for many years (up to 21 yrs), even as a first relapse site. These results could be important for potential future prophylactic BM strategies. [Table: see text].

Comparison of hormone receptor and HER2 status in resected brain metastases and primary breast cancer.

1117 Background: HER2 overexpresion and negative hormone receptors are reported as factors contributing to higher incidence of brain metastases (BM) in metastatic breast carcinoma. Therefore it could be expected that biological marker characteristics (BMC) of BM is consistent with primary breast carcinoma (PBC). Because few patients are eligible for surgery, BMC of BM is usually unknown. Methods: The aim of this analysis is to compare BMC in PBC and completely resected BM. Among 97 breast carcinoma patients with BM, 21 (21.6%) had 1-3 metastases, and underwent BM surgery. Results: All patients had pathologically confirmed BC metastases. BM BMC was known in 10/21 (47.6%). BMC is defined as ER/PR receptors (HR), (Quick score 0-8) and HER2 status (IHC 0-3+/CISH±). The only one HR+ PBC changed to HR – in BM. Among 8 HER2- PBC, 2 (25%) changed to HER2+ BM. All HR-, HER2+, and triple-negative PBC retained these BMC in BM (Table). Conclusions: According to our results, it could be expected that BM BMC profile is...