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Survival breast cancer brain metastases hemorrhage,communication skills lab non technical topics,gardening soil in pots - PDF 2016

Metastatic lesions to the brain occur commonly in oncology patients and portend a very poor outcome, as they often occur in the setting of progressive systemic metastatic disease and can result in neurologic deterioration that may preclude therapy.
The development of brain metastases is an unfortunate and common complication in oncology patients. Patients with brain metastases have a very poor prognosis—the median survival of untreated patients is approximately 1 month.[1] Death can be attributed to neurologic complications in around half of all patients, and to progression of systemic metastases in the rest. The exact population incidence of brain metastases is unknown, and the studies done to assess this issue are fraught with methodologic issues that make identification of time trends difficult. Patients with brain metastases typically present with signs of focal neurologic dysfunction. The treatment of patients with brain metastases is almost always administered with palliative intent, given the small likelihood of achieving long-term survival. Appropriate management of brain metastases requires a multidisciplinary approach, with input from several medical and ancillary specialties such as radiology, radiation and medical oncology, neurosurgery, neurology, psychiatry, and physical therapy. Optimal supportive care of a patient with brain metastases involves the use of steroids for cerebral edema (which occurs in almost all patients) and anticonvulsants for those who develop seizures (which occur in 20% to 30% of patients). The most common steroid used is dexamethasone—the choice of this particular agent is empiric, and other corticosteroids can be used effectively in this situation as well. Patients who present with or develop seizures require therapy with anticonvulsant drugs to control symptoms.
ABSTRACT: Small cell lung cancer (SCLC) accounts for approximately 20% of all cases of lung cancer.
Patients with SCLC are classified as having either limited- or extensive-stage disease according to the system developed by the Veteran's Administration Lung Cancer Study Group.[4] Patients with tumors that can easily be encompassed within an acceptable radiation portal (historically defined as a hemithorax) are classified as having limited disease, and they represent approximately one-third of all new SCLC cases.
The purpose of this paper is to provide an overview of the clinical presentation, diagnosis, and treatment of brain metastases in patients with SCLC, with a focus on current trends and developments in the treatment of this disease. Brain metastases most frequently arise at the junction between the white and grey matter, or the so called "watershed area" of the brain.[8] The signs and symptoms are not specific to the disease but rather reflect the location and number of metastatic lesions. The diagnosis of brain metastases is based on patient history, neurologic examination, and diagnostic imaging. In fact, SCLC is the most common histologic type of cancer associated with neurologic paraneoplastic syndromes.[ 9] These syndromes are thought to be related to an autoimmune process in which the tumor produces substances that are similar to those normally expressed by the nervous system.
Although patients with brain metastases have a poor prognosis overall, certain factors have been identified that are predictive for an improved outcome. Brain metastases require prompt intervention to minimize progressive neurologic injury.[10] The aim of initial management is to control increased intracranial pressure if it is present. Although brain metastases from SCLC can cause significant morbidity, it is rarely the sole cause of death.
The largest series documenting the role of WBRT in SCLC was reported in 1988 by Carmichael et al, who performed a retrospective review of 59 patients with proven brain metastases from SCLC treated with therapeutic irradiation from 1977 through 1983.[18] Although patients were treated with varying chemotherapy regimens, all those with brain metastases at presentation were given induction chemotherapy.
The European Organization for Research and Treatment of Cancer (EORTC) conducted a prospective, phase II study between 1989 and 1995 that accrued 22 patients with SCLC and brain-only metastases to evaluate the efficacy of WBRT as a single treatment modality.[23] Radiation consisted of 30 Gy in 10 fractions to the whole brain.
Many prospective trials have been conducted to identify the optimal dose and fractionation schedule in the treatment of patients with brain metastases. RTOG 9104 was a phase III study comparing accelerated hyperfractionation with standard accelerated fractionation in 429 patients with unresected brain metastases.[29] In this study, 39 patients had SCLC. Wong et al reported on the Mayo Clinic experience with reirradiation for brain metastases.[30] From 1975 through 1993, 86 patients were reirradiated because their neurologic function had deteriorated or findings on imaging studies were consistent with progressive disease after an initial course of WBRT, or both.
Neurologic symptoms were resolved in 27% of patients, 43% experienced a partial improvement, and 29% had either no change or their condition worsened after reirradiation.
Imanaka et al used reirradiation therapy in three patients with recurrent brain metastases from SCLC.[31] The initial therapy varied among the three patients.
Numerous retrospective studies have evaluated the effectiveness of stereotactic radiosurgery in the treatment of brain metastases. Sanghavi et al performed a retrospective review of 502 patients with brain metastases treated with radiosurgery and external beam radiation therapy at 10 institutions from January 1988 through May 1998.[33] Patients with brain metastases from any primary tumor treated with WBRT and a stereotactic radiosurgery boost to all visible lesions were included in this analysis.
On multivariate analysis, performance status, controlled primary disease, and absence of extracranial metastases were significant predictors of improved survival. RTOG 9508 was a phase III trial comparing WBRT alone vs WBRT followed by stereotactic radiosurgery for patients with one to three unresected brain metastases ? 4 cm from any primary tumor except for leukemia or lymphoma.[35] Patients were not stratified according to histology.
Patients treated with stereotactic radiosurgery were found to have a statistically significant improvement in the 1-year local control rate (82% vs 71%, P = .01). The relatively discrete nature of brain metastases suits the physical dose parameters of brachytherapy. McDermott et al reported on the University of California, San Francisco, experience in 30 patients with a single brain metastasis who underwent temporary I-125 implantation.[ 38] One of the patients included in this study had SCLC.
Breast cancer is the most common cancer in women in both developed and less developed regions in the world.
About 15% to 25% of invasive breast cancers have over-expression of erbB2 (HER2) receptors on the cell surface.
A better understanding of the role of HER2 signalling in breast cancer pathogenesis has led to the development of drugs that specifically target the HER2 receptor resulting in major improvement of outcome for this cancer.
Trastuzumab is an anti-HER2 monoclonal antibody that was shown to significantly increase the Time to Progression (TTP), Overall Survival (OS), and overall Response Rate (RR) when added to chemotherapy as a first-line treatment for HER2+ Metastatic Breast Cancer (MBC).  Trastuzumab was subsequently approved for use in the adjuvant setting for early HER2+ breast cancer. Studies have looked into blocking the HER2 receptor using two targeting agents with the aim of increasing the efficacy of treatment. Pertuzumab is a monoclonal antibody that binds to a different region of the HER2 extracellular domain than trastuzumab and can block dimerisation of HER2 with other HER family receptors. Trastuzumab-DM1 is an antibody-drug conjugate, with trastuzumab delivering the antimicrotubule agent DM1 (emtansine) to HER2-positive tumour cells. HER2 directed therapy has fundamentally changed the natural history of this otherwise aggressive type of breast cancer.
Dr Khoo Kei Siong presently serves as the Censor in the Council of the Academy of Medicine, Singapore. Dr Khoo graduated from the National University of Singapore and received his training in Internal Medicine and Medical Oncology at the Singapore General Hospital.
Data from several studies suggest that up to 40% of patients with certain metastatic cancers (eg, lung cancer) may develop brain metastases over their lifetime. Since brain metastases result in a significant degree of morbidity and mortality, therapy of this complication assumes importance in the overall care of the patient. The annual population incidence of central nervous system (CNS) metastases in Iceland was found to be 2.8 per 100,000 in a survey conducted in the 1950s to 1960s.
Certain commonly occurring cancers (eg, colon cancer) uncommonly metastasize to the brain, whereas some less prevalent cancers (eg, melanoma and renal cell cancer) seem to present with brain metastases relatively commonly.
For example, invasive procedures may not be required in a patient with known cancer with widespread metastases who presents with neurologic deficits and has characteristic imaging findings. The realistic goals of therapy for most patients with brain metastases are to improve symptoms and quality of life. The availability of systemic therapy options and the likelihood of response to such therapy depends on the nature of the primary tumor (eg, patients with metastatic breast cancer are more likely to have effective treatment options for systemic metastases than are those with metastatic melanoma).
The usual practice is to begin therapy with a total daily dose of 12 to 24 mg of dexamethasone (eg, 4 to 6 mg orally, every 6 hours), and to taper the dose as tolerated. No comparative studies have tested which of the available agents (eg, phenytoin, phenobarbital) is the most effective in this patient population. It tends to disseminate earlier in the course of its natural history than non-small cell lung cancer and is clinically more aggressive. In contrast, two-thirds of patients with SCLC present with extensive-stage disease, with frank distant sites of involvement that cannot be incorporated into a safe and tolerable radiation portal.[4] In that regard, metastases from SCLC have a particular predilection for the brain. Moreover, the severity of these symptoms may be a function of the degree of tumor-related vasogenic edema. Imaging of the brain is very important in patients with SCLC who are suspected of having brain metastases, because these patients often have metabolic abnormalities or paraneoplastic syndromes that can produce symptoms that mimic those caused by intracranial metastases.
These substances lead to the production of autoantibodies that crossreact with neuronal antigens and ultimately damage normal tissue. Gaspar et al performed a recursive partitioning analysis of 18 pretreatment characteristics and three treatment-related variables in three consecutive Radiation Therapy Oncology Group (RTOG) brain metastases trials conducted between 1979 and 1993.[11] The analysis included 1,200 patients, over 50% of whom had NSCLC.
This can be accomplished with the use of corticosteroids such as dexamethasone, which decreases the brain-to-tumor capillary permeability, thereby reducing edema of the brain.[6] Patients are typically prescribed dexamethasone (8 to 16 mg) divided into two to four daily doses. In addition, many of the patients included in these studies were also treated with chemotherapy, either concurrently with radiation or shortly thereafter.
However, the systemic treatment of patients with delayed presentation of brain metastases was individualized. Although these issues have not been addressed in a prospective fashion in the SCLC population alone, these patients were not specifically excluded from participation in these trials. The treatment options for these patients are often limited, and some authors have advocated repeat WBRT for palliation of symptoms.
The most common primary sites were the breasts and lung, but the proportion of patients with SCLC was not identified.
Two patients were treated with 30 Gy in 10 fractions to the whole brain, followed by a boost consisting of 10 Gy in four fractions for one patient and 9 Gy in three fractions for the other patient.

They are also minimally invasive and displace normal brain parenchyma, which reduces the risk of injury to healthy tissue. These studies have suggested that radiosurgery improves both control of intracranial metastases and survival.[33] However, the survival benefit suggested by these studies may have been due to bias because patients with known favorable prognostic factors were selected. Patients in this study were stratified according to their recursive partitioning analysis classification based on the RTOG's phase III brain metastases database reported by Gaspar et al (Table 1).[11] With this stratification system, current results can be compared with prior RTOG results.
Furthermore, all subsets of patients treated with stereotactic radiosurgery were more likely to have a stable or improved performance status than those receiving WBRT alone. Another approach to LDR brachytherapy involves permanent interstitial implants in which iodine (I)-125 sources that are embedded in suture material are inserted or implanted directly into a tumor cavity.
Of the 25 patients treated for recurrence of their metastasis, 4 received brachytherapy as a boost, and 1 had brachytherapy alone after resection without external irradiation. In Singapore, it accounts for 29% of all female cancers with an average of 1,700 new cases diagnosed each year from 2008 to 2012.
Multiple phase III trials showed that trastuzumab (in combination or subsequent to chemotherapy) was associated with nearly 50% improvements in disease-free survival and 30% reduction in the odds of death. In a phase III study, lapatinib plus trastuzumab significantly polonged median PFS compared with lapatinib alone in HER2+ MBC patients progressing on prior trastuzumab, although RRs were not significantly different. In preclinical models, T-DM1 has demonstrated inhibition of cellular proliferation and promotion of cell death in trastuzumab-resistant breast cancer cells.
Dr Khoo is a member of the American Society of Clinical Oncology, the European Society of Medical Oncology and a fellow of the Royal College of Physician in Edinburgh. Content and images are meant for practicing medical doctors, allied health care professionals and other establishments in the medical industry.
Materials and Methods: Among the patients who were followed-up and treated for breast cancer between January 2000 and January 2010, the ones with brain metastasis were included to the analysis.
The factors that have an impact on the development of brain metastasis in the patients with breast cancer. Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast. Vascular invasion in breast cancer; an overview of recent prognostic developments and molecular pathophysiological mechanisms.
Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer? Central nervous system metastases in women after multimodality therapy for high risk breast cancer. Human epidermal growth factor receptor 2 overexpression as a prognostic factor in a large tissue microarray series of node-negative breast cancers.
Molecular subtype approximated by quantitative estrogen receptor, progesterone receptor and Her2 can predict the prognosis of breast cancer. Clinical features and survival analysis of different subtypes of patients with breast cancer brain metastases. Identifying breast cancer patients at risk for central nervous system metastases in trials of the International Breast Cancer Study Group (IBCSG). Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer. Clinicopathologic characteristics of invasive lobular carcinoma of the breast: Results of an analysis of 530 cases from a single institution.
Invasive lobular carcinoma classic type: Response to primary chemotherapy and survival outcomes. Neoadjuvant chemotherapy: Not the best option in estrogen receptor-positive, HER2-negative, invasive classical lobular carcinoma of the breast? A comparative analysis of lobular and ductal carcinoma of the breast: Presentation, treatment, and outcomes.
Infiltrating lobular carcinoma of the breast clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns.
Human epidermal growth factor receptor 2 status correlates with lymph node involvement in patients with estrogen receptor (ER) negative, but with grade in those with ER-positive early-stage breast cancer suitable for cytotoxic chemotherapy.
Prognostic factors for skeletal complications from metastatic bone disease in breast cancer.
Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.
Lack of benefit of maintenance paclitaxel in first-line chemotherapy in metastatic breast cancer.
Can patients with metastatic breast cancer be cured after introduction of newer and more effective agents? The status of systemic metastases—their presence and rate of progression—is an important prognostic factor. The diagnosis requires use of imaging studies (magnetic resonance imaging [MRI] is the most sensitive method) and possibly a pathologic confirmation (surgical biopsy or resection), and infrequently involves the need to sample the cerebrospinal fluid (Figure 1). Some of the interventions discussed below have been demonstrated to moderately prolong survival in selected patient subsets. Steroids have multiple adverse effects, of which weight gain, psychosis, infection risk, long-term steroid dependence, and gastrointestinal bleeding are most troubling in this patient population.
Newer anticonvulsants (eg, levetiracetam [Keppra]) are being used more commonly, as they have fewer adverse effects and do not interfere with cytochrome p450-induced drug metabolism (which may be a consideration in some patients). Approximately 10% of patients present with brain metastases at the time of initial diagnosis, and an additional 40% to 50% will develop brain metastases some time during the course of their disease.
One such disorder, Eaton-Lambert myasthenic syndrome, is seen in up to 3% of patients with SCLC and causes proximal muscle weakness, autonomic dysfunction, and paresthesias. Antiepileptic medications such as phenytoin are not used routinely in this setting unless the patient presents with seizures.
As a result, few randomized trials have been conducted to guide the treatment evolution in this group of patients and to challenge the prevailing perspective that WBRT alone is the only effective treatment for brain metastases from SCLC. The radiation dose and fractionation schedules depended on the patient's performance and disease status and whether or not the patient had received previous prophylactic cranial irradiation (PCI).
The median duration of the response was 10 months in patients with a complete response and 5 months in patients with a partial response. For those receiving accelerated hyperfractionation, the entire brain was treated with 1.6 Gy bid to a total dose of 32 Gy in 20 fractions. The median time interval between the first and second courses of irradiation was 7.6 months.
In addition, the recursive partitioning analysis system attempts to remove the potential bias resulting from patient selection. All other smaller brain metastases were treated using the Gamma Knife system, with a mean prescription dose of 21.3 Gy. The radiosurgery doses were based on a previous RTOG trial and depended on the size of the lesion. There was no improvement in survival overall, but it did improve for recursive partitioning analysis class I patients, patients < 50 years of age, and patients with SCLC, any squamous cell cancers, or solitary brain metastases.
HER2 belongs to the human epidermal growth factor family of receptors (HER1 [EGFR], HER2, HER3, HER4). This was hailed as one of greatest breakthrough in breast cancer therapy in the last 20 years. Several phase III studies and a meta-analysis of trastuzumab and lapatinib either alone or in combination in the neoadjuvant setting showed that the pathological complete response rate is consistently the highest with the combination, suggesting that the optimal use of lapatinib may be in conjunction with trastuzumab.
Before he moved to his current practice, Dr Khoo was a Senior Consultant and Head of Department of Medical Oncology at the National Cancer Centre (NCC).
Metastatic breast cancer patients without brain metastasis, which had similar duration of follow-up and median age were included as the control group. Clinical trials are currently underway to define the optimal role of whole-brain radiation and radiosurgery in different subsets of patients. Even when brain metastases are suspected, the detection rate may depend on the availability of appropriate imaging technology.
Therefore, therapy directed toward extracranial metastases is also an essential component of treatment.
Several investigators have speculated that brain metastases have become an increasingly common problem in oncology patients due to improvements in diagnostic techniques as well as improvements in survival as a result of better therapies.[2] Due to the high prevalence of this problem, it is critical for the practicing oncologist to become aware of the issues involved in managing this complication. Once definitive therapy (eg, radiation) for the metastases is delivered, the steroid dose should be reduced as rapidly as tolerated in order to avoid these toxicities.
The prognosis of patients with brain metastases from SCLC is poor despite years of research.
The small number of patients with SCLC did not allow for this histology to be evaluated separately from other primaries.
The median survival of patients presenting with brain metastases was 7 months, compared with 3 months in patients with delayed development of metastatic disease. This trial confirmed a major finding from the previous retrospective studies-that a significant number of patients respond to WBRT, but the response duration and survival are short. The first two trials evaluated different accelerated fractionation regimens, including 40 Gy in 4 weeks, 40 Gy in 3 weeks, 30 Gy in 3 weeks, 30 Gy in 2 weeks, 10 Gy in one fraction, and 12 Gy in two fractions over 3 days.[27,28] The overall response to treatment was equivalent in all arms.

The median dose of the first course of WBRT was 30 Gy, which was usually given in 10 fractions. Radiographic abnormalities consistent with radiation changes appeared in five patients, and one patient developed symptoms of dementia, which was attributed to radiation therapy.
Re-treatment consisted of 20 Gy and was administered to two patients with hyperfractionation (20 fractions) and to one patient with conventional fractionation (10 fractions). New brain metastases detected on follow-up MRI scans were treated with repeat Gamma Knife radiosurgery. Therefore, the results of this study suggest that Gamma Knife radiosurgery appears to be as effective in treating brain metastases from SCLC as for those from NSCLC. The authors concluded that stereotactic radiosurgery can prolong survival in select patients with brain metastases only by 1 to 2 months. Oestrogen Receptor (ER), Progesterone Receptor (PR) and erbB2 (HER2) by immunohistochemistry are now part of routine histological evaluation of breast cancers.
Most of these tyrosine kinase receptors can be activated by the pairing of two of the same receptors (homodimerisation) or two different receptors (heterodimerisation) within the plasma membrane resulting in the activation of multiple signal transduction pathways. A year of treatment with trastuzumab given once every three weeks with a course of chemotherapy is now the standard of care for most if not all HER2+ early breast cancer.
A phase III ALTTO study is evaluating lapatinib, trastuzumab, trastuzumab followed by lapatinib, and both together in the adjuvant setting. He was the founding Director of the Division of Clinical Trials and Epidemiological Sciences and was instrumental in setting up the clinical trials capabilities in NCC.
Both group were compared for prognostic and predictive factors in terms of relationship between with or without brain metastasis and survival. In patients with breast cancer, brain involvement is approximately 10%-16% and this percentage increases to 30% in the autopsy series. The standard of care remains appropriate medical management followed by whole brain radiation therapy. Based on this analysis, age, performance status, control of the primary tumor, and the presence or absence of extracranial metastatic disease were found to significantly influence survival. Patients who received radiation doses of more than 40 Gy had longer response durations than those given lower doses. However, 40% of patients who received shortcourse brain irradiation had evidence of extracranial progressive disease at the time of treatment, whereas all patients who received extended-course brain irradiation were in partial or complete remission outside the brain. Median survival was 4.5 months in both arms, with a 1-year overall survival rate of 19% in the accelerated fractionation arm and 16% in the accelerated hyperfractionation arm.
From this review, the authors concluded that reirradiation should be offered to patients who develop progressive brain metastases.
The median survival times were longer in this study for each recursive partitioning analysis class than they were in the RTOG studies. Systemic disease remained the primary cause of death in more than two-thirds of the patients. The cancer stained negative for oestrogen and progesterone receptors but positive for erbB2 (HER2) receptor. HER2 over expression is confirmed by either a strong (3+) staining for erbB2 on immunohistochemistry or demonstration of amplification of erbB2 gene on fluorescence in-situ hybridisation.
In spite of the promise shown in these studies, in a phase III study directly comparing trastuzumab with lapatinib in combination with first-line taxane-based therapy, trastuzumab was shown to be superior with a longer PFS (11.4 vs. The addition of pertuzumab resulted in more diarrhoea and febrile neutropenia, but not cardiac dysfunction. T-DM1 is now approved as a second line treatment for HER2+ MBC patients previously treated with trastuzumab and a taxane. Results: There were a total of 63 female patients with metastatic breast cancer who had brain metastasis and the researchers enrolled the same number of female patients as the control group. In the current review, we discuss recent developments in the management of patients with brain metastases. Current research is evaluating novel agents in an attempt to improve the survival and quality of life in these patients. The authors concluded that the irradiation schedules customarily used to treat brain metastases in SCLC are unlikely to eradicate intracranial tumors in the occasional patient whose systemic cancer has a durable complete response. Given that higher radiation doses and altered fractionation schedules have not been shown to improve outcome in prospective trials, 30 Gy in 10 fractions continues to be one of the most commonly used fractionation schedules in WBRT.
Therefore, this study suggested that radiosurgery may improve survival in all patients with brain metastases regardless of recursive partitioning analysis class. The authors concluded that their experience with interstitial brachytherapy using I-125 implants was favorable and that interstitial brachytherapy is particularly useful in salvaging metastases that recur after prior therapies. Further staging evaluation with a Positron Emission Tomography (PET) scan showed that in addition to the breast tumour and axillary lymph nodes, there were multiple areas of increase uptake in the bones, liver, and lungs consistent with wide spread metastases.
Additionally, molecular profiling has led to classification of breast cancer into five distinct subtypes: Normal like, Luminal A, Luminal B, HER2+ and Basal-like.
A typical HER2+ breast cancer cells has 10 to 10,000 times the number of HER2 receptors on the cell surface compared to a HER2 negative cell. There are also ongoing researches to further refine the selection of patients who may benefit from HER2 directed therapy. In the univariate analysis, as a significant finding, it was found that, the patients with breast cancer who had brain metastasis had vascular invasion positivity, human epidermal growth factor receptor-2 (HER-2) positivity, a rare detection of invasive lobular carcinoma component in the tumor, estrogen receptor negativity, and no bone and liver metastasis and they did not receive chemotherapy due to several reasons after the detection of metastasis in any organ.
However, the most effective treatment for brain metastases from SCLC is the prevention of the development of clinically detectable disease.
They suggested that it may be appropriate to consider treatment with doses greater that 40 Gy. She was offered palliative therapy and was started on a combination of chemotherapy and Trastuzumab. HER2+ breast cancers grow more quickly and are associated with a poorer prognosis compared to their HER2-negative counterparts. Lapatinib is mainly used, in combination with chemotherapy or hormonal therapy, in trastuzumab-resistant patients. A phase III study (APHINITY) of trastuzumab and chemotherapy with or without pertuzumab in the adjuvant setting is ongoing. For patients with a complete response to initial treatment, prophylactic cranial irradiation is an effective method of prevention. Repeat PET scan after four cycles of treatment showed complete resolution of all sites of cancer. Therefore, the authors suggested that whole brain reirradiation is useful and safe for brain recurrence of SCLC. Hormonal therapy is the main stay of systemic therapy and chemotherapy has a lesser role in these tumours.
Currently, data about development of brain metastasis in breast cancer patients are quite inadequate and approaches, such as prophylactic radiotherapy (RT) similar to that used in small cell lung cancer and an established risk classification, are lacking. Therefore, we planned to conduct this study to evaluate the factors that have an impact on the development of brain metastasis in breast cancer patients.
The medical files of the patients were retrospectively examined and prognostic and predictive factors, information about the therapy and survival data were extracted from them.
As control group, patients with metastatic breast cancer without brain metastasis, which had similar duration of follow-up and median age were enrolled.The time from the diagnosis to the first detection of a recurrence in any organ was considered as disease-free survival (DFS), the time from the recurrence to the progression was considered as progression-free survival (PFS) and the time from the diagnosis to the death was considered as overall survival (OS).
The statistical analysis of the data was done using Statistical Package for Social Sciences for Windows (SPSS) Version 15.0 software. The mean of two groups was analyzed using t test, the independent group ratios were compared using chi-square test, the analysis between the predictors or independent variables and dependent variables was performed using logistic regression test, OS were analyzed using Kaplan-Meier method and two survival curves were compared using log-rank test. As control group, 63 patients with metastatic breast cancer without brain metastasis, which had similar duration of follow-up and median age were enrolled.Median ages of the patients were similar in both groups, with 49 (21-76) in the patient group with brain metastasis and 50 (29-72) in the control group. When both groups were compared in terms of CT application after the detection of the first metastasis in any organ, it was seen that the majority of the patients with brain metastasis did not receive CT (P=0.001). In the metastatic stage, of these 31 patients with HER-2 positive with brain metastasis, 17 (54.8) patients had received trastuzumab treatment however in without brain metastasis patients group, all HER-2 positive patients (10 patients, 100%) had received trastuzumab treatment. Survival Median follow-up was 34 (3-212) months in the patient group with brain metastasis and 43 (2-242) months in the control group [Table 1]. The rate of death was more than double in patients with brain metastasis compared to control group and this was statistically significant (P=0.001).
In patients with brain metastasis, brain was the first site of metastasis in 22 (34.9%) patients. Of the patients, 41 (65.1%) showed other organ metastasis, together with the brain metastasis. Multivariate analysis When the multivariate analysis was evaluated, it was seen that, in the patients with brain metastasis, greater number of HER-2 positive patients (P=0,001), without bone metastasis (P=0.035) and higher number of patients who did not receive CT after the occurrence of the first metastasis in any organ were found to be significant [Table 1].

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