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Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation

Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with... Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2013, Article ID 234391, 4 pages http://dx.doi.org/10.1155/2013/234391 Case Report Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation Esin Oktay, Özlem Yersal, Nezih Meydan, Mehmet SaLJroLlu, Ömer UyanJk, and Sabri Barutca Department of Medical Oncology, Faculty of Medicine, Adnan Menderes University, 09010 Aydın, Turkey Correspondence should be addressed to Esin Oktay; esin oktay@hotmail.com Received 13 July 2013; Accepted 2 September 2013 Academic Editors: L. Beex, J. I. Mayordomo, and O. Ozyilkan Copyright © 2013 Esin Oktay et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an eeff ctive treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine. 1. Introduction An invasive ductal carcinoma was diagnosed by core needle biopsy of the lesion and the tumor was estrogen receptor HER-2 overexpression is associated with poorer disease-free (ER)-negative, progesterone receptor (PgR)-negative, human and overall survival in breast cancer patients and with a epidermal growth factor receptor 2 (Her2)-positive (+++), tendency for visceral site metastasis [1]. Despite the positive and Ki-67 50%. After the modified radical mastectomy eeff ctonresponserateand overallsurvival, onethird of the operation, the pathological examination revealed that an patients treated with trastuzumab develop brain metastasis. invasive tumor was 5 cm in diameter and that 39 out of 40 Trastuzumab is a highly selective monoclonal antibody which lymph nodes were metastatic. targets the extracellular domain of the HER2 receptor and She received four cycles of EC (90/600 mg/m doses, does not fully cross the blood-brain barrier (BBB). resp.) chemotherapy regimen followed by weekly pacli- Lapatinib is an oral small molecule tyrosine kinase taxel and trastuzumab combination (paclitaxel 80 mg/m ; inhibitor which targets the C-terminus domain of both the trastuzumab 2 mg/kg aeft r the loading dose of 4 mg/kg) for HER2 and EGFR receptors. Due to its small size, it can be 12 weeks. At the end of the paclitaxel treatment, trastuzumab across the BBB more eecti ff ve than the larger trastuzumab was planned 6 mg/kg maintenance dose every 21 days for molecule [2]. Here, we report a patient with HER-2 over- totally one year. expressing breast cancer where brain metastases were suc- However, after the rst fi course of the maintenance cessfully treated with lapatinib and capecitabine combination trastuzumab, she complained of dizziness and progressive regimen. imbalance. Magnetic resonance imaging (MRI) of the brain revealed multiple brain lesions in cerebellum, periventricular, and supraventricular white matter accompanied by promi- 2. Case Presentation nent vasogenic edema (Figure 1). The patient received whole brain radiation therapy with a total dose of 3000 cGy which A forty-three-years old female patient was admitted to our hospital duetothe rightbreastmass. Bilateralmammography was administered in 10 fractions of 300 cGy. Aeft r the comple- revealed an ill-defined 15 mm mass lesion in the right breast. tion of radiotherapy, lapatinib and capecitabine combination 2 Case Reports in Oncological Medicine Figure 1: Magnetic resonance imaging scans demonstrating multiple brain lesions. (1250 mg/day and 1500 mg twice daily, 14/21 days, resp.) was Several retrospective analyses of HER2 positive meta- started. Control MRI showed stable brain metastases one static BC patients treated with trastuzumab-based therapies month later. A partial CNS response was documented with showed that about 30% of these patients develop BMs [2], adecreaseofabout 30%inher brainmetastasesaeft rtwo andinmorethan50% of thesecases,BMs occurinpatients cycles of chemotherapy. Metastatic lesions kept regressing till with either responsive or stable disease at extracranial sites. sixth month of treatment and there were no masses except This patient developed brain metastases under treatment with milimetric cerebellar metastases on MRI (Figure 2). They are trastuzumab in the adjuvant setting. stable at eighteen months of therapy while there are no other Trastuzumab has limited penetration through the blood visseral metastases. brain barrier. eTh ratio of trastuzumab level in serum to cerebrospinal uid fl is found to be 430 : 1, thus making the brain vulnerable for the development of metastases [1]. 3. Discussion Lapatinib is a small molecule and reversible inhibitor of both HER1 and HER2. Its molecular weight is very low (<1 kDa). It Human epidermal growth factor receptor 2 (HER2/ErbB2) is has theoretical ability to cross the BBB. Preclinically this has a member of the ErbB family of tyrosine kinase receptors. been demonstrated in mice with HER-2 overexpressing brain Activation of HER2 regulates normal cell growth; dysregu- metastases. Treatment with lapatinib resulted in a significant lated HER2 activation supports tumorigenesis via cell pro- decrease in tumor volume which was attributed to a decrease liferation, migration, survival, and angiogenesis [3]. HER2- in HER-2 phosphorylation and cell proliferation [5]. A positive tumors occur in 25% of all breast cancers [1]. phaseIIstudy with single agentlapatinib 750mgbid was Overexpression of HER2 indicates poor prognostic factor undertaken in patients with HER2-positive CNS metastases foroverall anddisease-freesurvival, anditisarisk factor for who had shown progression in CNS lesions aer ft whole-brain thedevelopment of brainmetastases. Gabosetal. followed radiotherapy, and clinical and radiological responses were up 301 Her2-positive and 363 Her2-negative breast cancer observed [6]. patients during 3.9 years. Brain metastasis was found to be 9% in Her2-positive cases and 1.9% in those with negative Her2 Most clinical or preclinical data showed that lapatinib [4]. and capacitabine combination therapy is more effective than Case Reports in Oncological Medicine 3 Figure 2: Magnetic resonance imaging scans demonstrating near complete resolution of brain metastases aer ft lapatinib plus capecitabine treatment. lapatinib or capacitabine monotherapy in breast cancer with metastases as site of rfi st progression, the combination of brain metastases. In a phase II trial, HER2 positive metastatic lapatinib plus capecitabine achieved a significant reduction breast cancer patients who developed brain metastases aeft r in the incidence of brain metastases as site of rfi st progression trastuzumab therapy were treated with lapatinib monother- (2% versus 6%;𝑃=0.045 )[10]. apy. Seven % of patients had >50% reduction in brain In the Lapatinib Expanded Acces Program (LEAP), 138 metastasis volume, 6% had a partial response, and 42% had patients with progresive CNS metastases (patients received stable diseaseinmorethan8weeks[7]. Patients whose CNS prior capacitabine therapy) were enrolled, and the CNS disease was progresssed on lapatinib treatment, capecitabine objective response rate was 18% with combined lapatinib plus and lapatinib was administered. Twenty % of patients had capacitabine [11]. 50% reduction in tumor volume, 20% of patients had partial In some studies, other agents were used instead of cape- CNS response, 39% had stable disease in more than 8 weeks citabine. A phase II study tested lapatinib plus capecitabine [8]. versus lapatinib plus topotecan in patients with HER2+ This case report describes the near complete resolution breast cancer with brain metastases. The primary end point of brain metastases in a 43-year-old woman with HER2- was CNS objective response. No response was observed in positive metastatic breast cancer who was treated with a lapatinibplustopotecan arm. eTh objectiveresponseratein combination of lapatinib plus capecitabine. This result is the lapatinib plus capacitabine arm was 38% [12]. in agreement with previous reports that this combination In conclusion, trastuzumab treatment does not prevent is more eecti ff ve in treatment of brain metastases. In the intracranial seeding and is largely ineffective for established LANDSCAPE trial, 45 patients with brain metastases from CNS disease. Today, women with HER2-positive BM are HER2+ breast cancer received lapatinib plus capecitabine surviving longer. Most clinical studies show that LC is an prior to radiation therapy, reported a CNS objective response active combination aeft r the development of BMs and may of 67%, with a median time to tumor progression of 5.5 further improve the prognosis of patients with BMs from months [9]. HER2+ BC compared with the trastuzumab-based therapies. In randomized phase III trial (EGF100151) lapatinib This patient had nearly complete response with this com- plus capacitabine versus capacitabine for incidence of brain bination therapy. She has been alive without any complaint 4 Case Reports in Oncological Medicine for eighteen months. There is no progresion in CNS lessions alone in women with advanced breast cancer that has pro- gressed on trastuzumab: updated efficacy and biomarker anal- and there is no other visseral metastases. Based on our single yses,” Breast Cancer Research and Treatment,vol.112,no. 3, pp. case observation, capacitabine and lapatinib combination 533–543, 2008. therapy seems as the best choice for breast cancer patients [11] R. Greil, S. Borˇstnar, K. Petrak ´ ova´ et al., “Combination therapy with only CNS metastases. of lapatinib and capecitabine for ErbB2-positive metastatic On the other hand, prevention from BM is important or locally advanced breastcancer: results from the lapatinib too. Many risk factors are associated with the development of expanded accessprogram (LEAP) in central and Eastern BM, such as young age, hormone receptor-negative primary Europe,” Onkologie,vol.34, no.5,pp. 233–238, 2011. tumors, HER2+ tumors, and heavy burden of disease (large [12] N. U. Lin, W. Eierman, R. Greil et al., “Randomized phase II primary tumors, lymph node involvement, prior lung, liver, study of lapatinib plus capecitabine or lapatinib plus topotecan or bone metastases, increased number of metastatic sites, and for patients with HER2-positive breast cancer brain metastases,” elevated lactate dehydrogenase [LDH] levels) [1]. In breast Journal of Neuro-Oncology,vol.105,no. 3, pp.613–620,2011. cancer patients with high risk of brain metastasis, whole- brain irradiation may be studied in controlled clinical trials. References [1] G. Tomasello, P. L. Bedard, E. de Azambuja, D. Lossignol, D. Devriendt, and M. J. Piccart-Gebhart, “Brain metastases in HER2-positive breast cancer: the evolving role of lapatinib,” Critical Reviews in Oncology/Hematology,vol.75, no.2,pp. 110– 121, 2010. [2] G. Metro, J. Foglietta, M. Russillo et al., “Clinical outcome of patients with brain metastases from HER2-positive breast can- cer treated with lapatinib and capecitabine,” Annals of Oncology, vol. 22, no. 3, pp. 625–630, 2011. [3] Y. Yarden, “eTh EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities,” Euro- pean Journal of Cancer, vol. 37, supplement 4, pp. S3–S8, 2001. [4] Z. Gabos, R. Sinha, J. Hanson et al., “Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis aer ft newly diagnosed breast cancer,” Journal of Clinical Oncology, vol. 24, no. 36, pp. 5658– 5663, 2006. [5] B.Gril,D.Palmieri,J.L.Bronderetal.,“Eeff ctoflapatinibonthe outgrowth of metastatic breast cancer cells to the brain,” Journal of the National Cancer Institute,vol.100,no. 15,pp. 1092–1103, [6] N. U. Lin, L. A. Carey, M. C. Liu et al., “Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer,” Journal of Clinical Oncology,vol.26, no.12, pp.1993–1999,2008. [7] N. U. Lin, V. Dieras, D. Paul et al., “EGF105084, a phase II study of lapatinib for brain metastases in patients with HER2+ breast cancer following trastuzumab based systemic therapy and cranial radiotherapy,” Journal of Clinical Oncology,vol.25, supplement, no. 18, 2007. [8] N. U. Lin, D. Paul, V. Dieras et al., “Lapatinib and capecitabine for the treatment of brain metastases in patients with HER2+ breast cancer: an updated analysis from EGF105084,” in Pro- ceedings of the 30th Annual San Antonio Breast Cancer Sympo- sium (SABCS ’07),San Antonio,Tex,USA,December2007. [9] T. Bachelot, G. Romieu, M. Campone et al., “Lapatinib plus capecitabine in patients with previously untreated brain metas- tases from HER2-positive metastatic breast cancer (LAND- SCAPE): a single-group phase 2 study,” The Lancet Oncology , vol. 14,no. 1, pp.64–71,2013. [10] D. Cameron, M. Casey, M. Press et al., “A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Case Reports in Oncological Medicine Hindawi Publishing Corporation

Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation

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Copyright © 2013 Esin Oktay et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract

Hindawi Publishing Corporation Case Reports in Oncological Medicine Volume 2013, Article ID 234391, 4 pages http://dx.doi.org/10.1155/2013/234391 Case Report Nearly Complete Response of Brain Metastases from HER2 Overexpressing Breast Cancer with Lapatinib and Capecitabine after Whole Brain Irradiation Esin Oktay, Özlem Yersal, Nezih Meydan, Mehmet SaLJroLlu, Ömer UyanJk, and Sabri Barutca Department of Medical Oncology, Faculty of Medicine, Adnan Menderes University, 09010 Aydın, Turkey Correspondence should be addressed to Esin Oktay; esin oktay@hotmail.com Received 13 July 2013; Accepted 2 September 2013 Academic Editors: L. Beex, J. I. Mayordomo, and O. Ozyilkan Copyright © 2013 Esin Oktay et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Trastuzumab treatment does not prevent intracranial seeding and is largely ineffective for established central nervous system metastasis in HER2 overexpressing breast cancer patients. Combination therapy of lapatinib and capecitabine may be an eeff ctive treatment option for brain metastasis of HER2-positive breast cancer. We report a patient with breast cancer overexpressing HER-2 where brain metastases were successfully treated with radiation and a combination of lapatinib and capecitabine. 1. Introduction An invasive ductal carcinoma was diagnosed by core needle biopsy of the lesion and the tumor was estrogen receptor HER-2 overexpression is associated with poorer disease-free (ER)-negative, progesterone receptor (PgR)-negative, human and overall survival in breast cancer patients and with a epidermal growth factor receptor 2 (Her2)-positive (+++), tendency for visceral site metastasis [1]. Despite the positive and Ki-67 50%. After the modified radical mastectomy eeff ctonresponserateand overallsurvival, onethird of the operation, the pathological examination revealed that an patients treated with trastuzumab develop brain metastasis. invasive tumor was 5 cm in diameter and that 39 out of 40 Trastuzumab is a highly selective monoclonal antibody which lymph nodes were metastatic. targets the extracellular domain of the HER2 receptor and She received four cycles of EC (90/600 mg/m doses, does not fully cross the blood-brain barrier (BBB). resp.) chemotherapy regimen followed by weekly pacli- Lapatinib is an oral small molecule tyrosine kinase taxel and trastuzumab combination (paclitaxel 80 mg/m ; inhibitor which targets the C-terminus domain of both the trastuzumab 2 mg/kg aeft r the loading dose of 4 mg/kg) for HER2 and EGFR receptors. Due to its small size, it can be 12 weeks. At the end of the paclitaxel treatment, trastuzumab across the BBB more eecti ff ve than the larger trastuzumab was planned 6 mg/kg maintenance dose every 21 days for molecule [2]. Here, we report a patient with HER-2 over- totally one year. expressing breast cancer where brain metastases were suc- However, after the rst fi course of the maintenance cessfully treated with lapatinib and capecitabine combination trastuzumab, she complained of dizziness and progressive regimen. imbalance. Magnetic resonance imaging (MRI) of the brain revealed multiple brain lesions in cerebellum, periventricular, and supraventricular white matter accompanied by promi- 2. Case Presentation nent vasogenic edema (Figure 1). The patient received whole brain radiation therapy with a total dose of 3000 cGy which A forty-three-years old female patient was admitted to our hospital duetothe rightbreastmass. Bilateralmammography was administered in 10 fractions of 300 cGy. Aeft r the comple- revealed an ill-defined 15 mm mass lesion in the right breast. tion of radiotherapy, lapatinib and capecitabine combination 2 Case Reports in Oncological Medicine Figure 1: Magnetic resonance imaging scans demonstrating multiple brain lesions. (1250 mg/day and 1500 mg twice daily, 14/21 days, resp.) was Several retrospective analyses of HER2 positive meta- started. Control MRI showed stable brain metastases one static BC patients treated with trastuzumab-based therapies month later. A partial CNS response was documented with showed that about 30% of these patients develop BMs [2], adecreaseofabout 30%inher brainmetastasesaeft rtwo andinmorethan50% of thesecases,BMs occurinpatients cycles of chemotherapy. Metastatic lesions kept regressing till with either responsive or stable disease at extracranial sites. sixth month of treatment and there were no masses except This patient developed brain metastases under treatment with milimetric cerebellar metastases on MRI (Figure 2). They are trastuzumab in the adjuvant setting. stable at eighteen months of therapy while there are no other Trastuzumab has limited penetration through the blood visseral metastases. brain barrier. eTh ratio of trastuzumab level in serum to cerebrospinal uid fl is found to be 430 : 1, thus making the brain vulnerable for the development of metastases [1]. 3. Discussion Lapatinib is a small molecule and reversible inhibitor of both HER1 and HER2. Its molecular weight is very low (<1 kDa). It Human epidermal growth factor receptor 2 (HER2/ErbB2) is has theoretical ability to cross the BBB. Preclinically this has a member of the ErbB family of tyrosine kinase receptors. been demonstrated in mice with HER-2 overexpressing brain Activation of HER2 regulates normal cell growth; dysregu- metastases. Treatment with lapatinib resulted in a significant lated HER2 activation supports tumorigenesis via cell pro- decrease in tumor volume which was attributed to a decrease liferation, migration, survival, and angiogenesis [3]. HER2- in HER-2 phosphorylation and cell proliferation [5]. A positive tumors occur in 25% of all breast cancers [1]. phaseIIstudy with single agentlapatinib 750mgbid was Overexpression of HER2 indicates poor prognostic factor undertaken in patients with HER2-positive CNS metastases foroverall anddisease-freesurvival, anditisarisk factor for who had shown progression in CNS lesions aer ft whole-brain thedevelopment of brainmetastases. Gabosetal. followed radiotherapy, and clinical and radiological responses were up 301 Her2-positive and 363 Her2-negative breast cancer observed [6]. patients during 3.9 years. Brain metastasis was found to be 9% in Her2-positive cases and 1.9% in those with negative Her2 Most clinical or preclinical data showed that lapatinib [4]. and capacitabine combination therapy is more effective than Case Reports in Oncological Medicine 3 Figure 2: Magnetic resonance imaging scans demonstrating near complete resolution of brain metastases aer ft lapatinib plus capecitabine treatment. lapatinib or capacitabine monotherapy in breast cancer with metastases as site of rfi st progression, the combination of brain metastases. In a phase II trial, HER2 positive metastatic lapatinib plus capecitabine achieved a significant reduction breast cancer patients who developed brain metastases aeft r in the incidence of brain metastases as site of rfi st progression trastuzumab therapy were treated with lapatinib monother- (2% versus 6%;𝑃=0.045 )[10]. apy. Seven % of patients had >50% reduction in brain In the Lapatinib Expanded Acces Program (LEAP), 138 metastasis volume, 6% had a partial response, and 42% had patients with progresive CNS metastases (patients received stable diseaseinmorethan8weeks[7]. Patients whose CNS prior capacitabine therapy) were enrolled, and the CNS disease was progresssed on lapatinib treatment, capecitabine objective response rate was 18% with combined lapatinib plus and lapatinib was administered. Twenty % of patients had capacitabine [11]. 50% reduction in tumor volume, 20% of patients had partial In some studies, other agents were used instead of cape- CNS response, 39% had stable disease in more than 8 weeks citabine. A phase II study tested lapatinib plus capecitabine [8]. versus lapatinib plus topotecan in patients with HER2+ This case report describes the near complete resolution breast cancer with brain metastases. The primary end point of brain metastases in a 43-year-old woman with HER2- was CNS objective response. No response was observed in positive metastatic breast cancer who was treated with a lapatinibplustopotecan arm. eTh objectiveresponseratein combination of lapatinib plus capecitabine. This result is the lapatinib plus capacitabine arm was 38% [12]. in agreement with previous reports that this combination In conclusion, trastuzumab treatment does not prevent is more eecti ff ve in treatment of brain metastases. In the intracranial seeding and is largely ineffective for established LANDSCAPE trial, 45 patients with brain metastases from CNS disease. Today, women with HER2-positive BM are HER2+ breast cancer received lapatinib plus capecitabine surviving longer. Most clinical studies show that LC is an prior to radiation therapy, reported a CNS objective response active combination aeft r the development of BMs and may of 67%, with a median time to tumor progression of 5.5 further improve the prognosis of patients with BMs from months [9]. HER2+ BC compared with the trastuzumab-based therapies. In randomized phase III trial (EGF100151) lapatinib This patient had nearly complete response with this com- plus capacitabine versus capacitabine for incidence of brain bination therapy. She has been alive without any complaint 4 Case Reports in Oncological Medicine for eighteen months. There is no progresion in CNS lessions alone in women with advanced breast cancer that has pro- gressed on trastuzumab: updated efficacy and biomarker anal- and there is no other visseral metastases. Based on our single yses,” Breast Cancer Research and Treatment,vol.112,no. 3, pp. case observation, capacitabine and lapatinib combination 533–543, 2008. therapy seems as the best choice for breast cancer patients [11] R. Greil, S. Borˇstnar, K. Petrak ´ ova´ et al., “Combination therapy with only CNS metastases. of lapatinib and capecitabine for ErbB2-positive metastatic On the other hand, prevention from BM is important or locally advanced breastcancer: results from the lapatinib too. Many risk factors are associated with the development of expanded accessprogram (LEAP) in central and Eastern BM, such as young age, hormone receptor-negative primary Europe,” Onkologie,vol.34, no.5,pp. 233–238, 2011. tumors, HER2+ tumors, and heavy burden of disease (large [12] N. U. Lin, W. Eierman, R. Greil et al., “Randomized phase II primary tumors, lymph node involvement, prior lung, liver, study of lapatinib plus capecitabine or lapatinib plus topotecan or bone metastases, increased number of metastatic sites, and for patients with HER2-positive breast cancer brain metastases,” elevated lactate dehydrogenase [LDH] levels) [1]. In breast Journal of Neuro-Oncology,vol.105,no. 3, pp.613–620,2011. cancer patients with high risk of brain metastasis, whole- brain irradiation may be studied in controlled clinical trials. References [1] G. Tomasello, P. L. Bedard, E. de Azambuja, D. Lossignol, D. Devriendt, and M. J. Piccart-Gebhart, “Brain metastases in HER2-positive breast cancer: the evolving role of lapatinib,” Critical Reviews in Oncology/Hematology,vol.75, no.2,pp. 110– 121, 2010. [2] G. Metro, J. Foglietta, M. Russillo et al., “Clinical outcome of patients with brain metastases from HER2-positive breast can- cer treated with lapatinib and capecitabine,” Annals of Oncology, vol. 22, no. 3, pp. 625–630, 2011. [3] Y. Yarden, “eTh EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities,” Euro- pean Journal of Cancer, vol. 37, supplement 4, pp. S3–S8, 2001. [4] Z. Gabos, R. Sinha, J. Hanson et al., “Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis aer ft newly diagnosed breast cancer,” Journal of Clinical Oncology, vol. 24, no. 36, pp. 5658– 5663, 2006. [5] B.Gril,D.Palmieri,J.L.Bronderetal.,“Eeff ctoflapatinibonthe outgrowth of metastatic breast cancer cells to the brain,” Journal of the National Cancer Institute,vol.100,no. 15,pp. 1092–1103, [6] N. U. Lin, L. A. Carey, M. C. Liu et al., “Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer,” Journal of Clinical Oncology,vol.26, no.12, pp.1993–1999,2008. [7] N. U. Lin, V. Dieras, D. Paul et al., “EGF105084, a phase II study of lapatinib for brain metastases in patients with HER2+ breast cancer following trastuzumab based systemic therapy and cranial radiotherapy,” Journal of Clinical Oncology,vol.25, supplement, no. 18, 2007. [8] N. U. Lin, D. Paul, V. Dieras et al., “Lapatinib and capecitabine for the treatment of brain metastases in patients with HER2+ breast cancer: an updated analysis from EGF105084,” in Pro- ceedings of the 30th Annual San Antonio Breast Cancer Sympo- sium (SABCS ’07),San Antonio,Tex,USA,December2007. [9] T. Bachelot, G. Romieu, M. Campone et al., “Lapatinib plus capecitabine in patients with previously untreated brain metas- tases from HER2-positive metastatic breast cancer (LAND- SCAPE): a single-group phase 2 study,” The Lancet Oncology , vol. 14,no. 1, pp.64–71,2013. [10] D. Cameron, M. Casey, M. Press et al., “A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

Journal

Case Reports in Oncological MedicineHindawi Publishing Corporation

Published: Sep 26, 2013

References