Cem Boruban

Biological Subtypes and Survival Outcomes in Breast Cancer Patients with Brain Metastases (Study of the Anatolian Society of Medical Oncology)

Background: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients.

Lapatinib plus Capecitabine for HER2-Positive Advanced-Stage Breast Cancer in Elderly Women: Review of the Anatolian Society of Medical Oncology (ASMO) Experience.

Background: The efficacy and safety of the lapatinib and capecitabine combination remain elusive in elderly patients with metastatic breast cancer (MBC), who progress after trastuzumab-based therapy. Patients and Methods: A total of 26 patients with HER2-positive MBC were included in this retrospective multicenter study. Median age was 69 years (range 65-82 years). All patients were treated with the combination of lapatinib (1,250 mg/day, continuously) and capecitabine (2,000 mg/m2 on days 1-14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. Results: The median follow-up was 10 months (range 2-31 months). An overall response rate of 33.4% was achieved, including 1 complete response (3.8%), and 8 partial responses (30.8%). Median progression-free survival was 7 months (95% confidence interval (CI) 5-8), and the median overall survival was 15 months (95% CI 11-19). Most common side effects were fatigue (53.8%), diarrhea (46%), vomiting (36.3%), hand-foot syndrome (34.5%), and anorexia (34.6%). Grade 3-4 toxicities were identified as hand-foot syndrome (3.8%), diarrhea (7.6%), and fatigue (11.5%). There were no symptomatic cardiac events. Conclusion: Lapatinib and capecitabine combination therapy was effective and well tolerated in elderly patients with MBC, who had progressive disease after trastuzumab-based therapy.

Lapatinib plus Capecitabine for Brain Metastases in Patients with Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: A Review of the Anatolian Society of Medical Oncology (ASMO) Experience

Background: We investigated the clinical outcome of patients with brain metastases (BMs) from human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) treated with lapatinib and capecitabine (LC). Patients and Methods: A total of 203 patients with HER2+ MBC, who had progressed after trastuzumab-containing chemotherapy, were retrospectively evaluated in 11 centers between September 2009 and May 2011. 85 patients who had developed BMs before the initiation of treatment with LC were included. All patients had received prior cranial radiotherapy. All patients were treated with the combination of lapatinib (1,250 mg/day continuously) and capecitabine (2,000 mg/m2 on days 1–14 of a 21-day cycle). Results: The median follow-up was 10.5 months (range 1–38 months). An overall response rate of 27.1% was achieved, including complete response in 2 (2.4%) and partial response in 21 (24.7%) patients. Median progression-free survival was 7 months (95% confidence interval (CI) 5–9), with a median overall survival of 13 months (95% Cl 9–17). The most common side effects were hand-foot syndrome (58.8%), nausea (55.3%), fatigue (48.9%), anorexia (45.9%), rash (36.5%), and diarrhea (35.4%). Grade 3–4 toxicities were hand-foot syndrome (9.4%), diarrhea (8.3%), fatigue (5.9%), and rash (4.7%). There were no symptomatic cardiac events. Conclusion: LC combination therapy was effective and well-tolerated in patients with HER2+ MBC with BMs, who had progressive disease after trastuzumab-containing therapy.

Lapatinib plus capecitabine for HER2-positive advanced breast cancer: a multicentre study of Anatolian Society of Medical Oncology (ASMO)

Abstract Lapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR). The present study evaluated the efficacy and tolerability of the combination of lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total of 203 patients with a median age of 48 years (range: 25–82 years) were evaluated retrospectively in 11 centres between September 2007 and May 2011. All the patients had HER2-positive MBC progressing after trastuzumab and chemotherapy including an anthracycline and/or taxane. All patients were treated with the combination of lapatinib (1250 mg/day, continuously) and capecitabine (2000 mg/m2 on days 1 through 14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. The median follow-up was 10·7 months (range: 1–40 months). An overall response rate (ORR) of 33·4% was achieved including 7 complete responses (CR, 3·4%), 61 partial responses (PR, 30·0%), and 44 stable disease (37·9%). Clinical benefit rate of 71·3% was achieved. Median progression-free survival (PFS) was 7 months (95% CI: 6–10 months), with a median overall survival (OS) of 15 months (95% CI: 12–18 months). The most common side effects were hand–foot syndrome (46·8%), nausea (42·3%), fatigue (42·2%), anorexia (38·5%), diarrhea (31·5%), and rash (29·6%). Grade 3–4 toxicities were identified as hand foot syndrome (7·9%), diarrhea (6·9%), fatigue (5·9%), and rash (5·4%). There were no symptomatic cardiac events. Lapatinib and capecitabine combination therapy is effective and well tolerated in patients with MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline therapy, as evidenced by this retrospective evaluation. Toxicity was mild to moderate with low grade 3–4 toxicity.

Pathologic and Clinical Characteristics of Elderly Patients With Breast Cancer: A Retrospective Analysis of a Multicenter Study (Anatolian Society of Medical Oncology)

There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.

Synchronous presentation of nasopharyngeal and renal cell carcinomas

We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.

The role of insulin-like growth factor-I receptor in the development of Herceptin resistance.

To the Editor: We read with great interest the article by Tanner et al. regarding development of a novel cell line established from patient with Herceptin-resistant breast cancer ([1][1]). They showed that lack of growth inhibition was rationalized by the unaltered Akt phosphorylation in these

Recent Findings for Anti-Metastatic Potential of Heparin

Low-molecular-weight heparins (LMWHs) have been used in both the prevention and treatment of thromboembolic disease in patients with malignancy. Retrospective analyses of clinical trials in which LMWHs had been used to treat established thrombosis in cancer patients have shown a survival advantage for the treated groups (1–3). More recently, a clinical trial in patients with small-cell lung carcinoma showed improved progression-free and overall survival for patients who received LMWH for 18 weeks (4). In 2005, two additional randomized studies reported on the potential benefits of longer term LMWH therapy for cancer patients. The first, by Lee and colleagues (5) was the longterm follow-up of patients in the comparison of LMWH vs. oral anticoagulant therapy for longterm anticoagulation in cancer patients with venous thromboembolism (CLOT) trial. This trial showed that there is a survival benefit with LMWH therapy in the subgroup of patients without evident metastatic disease at the time of random assignment to treatment. A second study, by Klerk and colleagues (6), showed the value of up to 6 weeks of LMWH therapy compared with placebo in patients with advanced malignant disease. A variety of tumor types were included in this study and for both the overall trial population and for a subgroup of patients with better prognosis at the time of random assignment, LMWH therapy was associated with a significant survival advantage. Currently, the exact mechanisms for a potential antineoplastic effect of low molecular weight heparins remain unknown. These positive outcomes in LMWH therapy arm in all trials above might be explained by its antiangiogenic effect (7). Interestingly, recent studies suggested a new mechanism of its action on tumor cells. Chemokines and their respective receptors expression have recently been demonstrated in the development of primary tumors and metastases (8). In particular chemokine receptors CXR4 and CCR7 are highly expressed in malignant breast tumors and metastases. Their respective ligands stromal cell-derived factor-1 (CXCL12/SDF-1) and CCL21/6Ckine are expressed in organs that represent important sites of breast cancer metastasis such as bone marrow, liver, and lung (9). This mechanism has also been implicated in other cancers. It is well known that chemokines also promote specific leukocyte extravasation at sites of inflammation. It was reported that disaccharides (DS), generated by enzymatic degradation of heparin or heparan sulfate, inhibit T cell–mediated immune reactions in rodents and regulate cytokine (tumor necrosis factor–α, interleukin-8, and interleukin-1β) secretion by T cells, macrophages, or intestinal epithelial cells (10). Recent study showed that DS can regulate inflammation by inhibiting CXCL12-dependent migration in vitro and in vivo and decreasing CXCL12-induced T cell adhesion to the extracellular matrix glycoprotein, fibronectin (11). Furthermore, Harvey and colleagues (12) have investigated the effects of heparins upon an in vitro model of breast cancer. Results provided evidence that heparin completely inhibits chemotaxis of these cancer cells by inhibiting the binding of CXCL12 to its receptor and its subsequent activation. A recent study by Veldkamp and colleagues (13) may give us a clue how heparin inhibits CXCL12. They found that acidic pH promotes the monomeric state of CXCL12 by destabilizing the dimeric structure, while heparin binding promotes CXCL12 dimer formation. Although it is not known whether the monomeric or dimeric structure of CXCL12 is responsible for signaling in vivo, we can speculate that heparin might