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Breast Cancers with Brain Metastases

Introduction Breast cancer is the most common carcinoma in women, accounting for 23% of all female cancers globally ( ). The etiology of breast cancer is multifactorial, involving diet, reproductive factors, and hormones. The overall incidence is higher in developed countries. Breast carcinoma usually presents with a palpable mass, but less commonly, skin retraction, nipple inversion, nipple discharge, change in the size or shape of the…

New Targeted Therapies for Brain Metastases from Breast and Lung Cancer and Melanoma

Introduction Brain metastases (BM) are an important cause of morbidity and mortality and represent the most common intracranial tumors in adults, occurring in ∼20–30% of cancer patients ( ; ). With advances in diagnostic techniques and improvements in the treatment of systemic disease, the incidence of BM is increasing ( ). Regardless of the treatment, the outcome of patients with BM remains poor. The latter provides…

Brain Metastasis from Breast Cancer: Molecular Mechanisms

Introduction Breast cancer is a frequent source of systemic metastatic disease. The spread of cancer cells, from a primary location to multiple sites in the body, was first labeled as “metastasis” (Greek: displacement, μɛτα′ = next + στα′σιζ = placement) by Jean Claude Recamier in 1829. The dissemination of breast cancer to the central nervous system has been reported by to occur in approximately 30% of patients with invasive breast cancer. Consequently,…

Brain Metastasis in Patients with Non-Small Cell Lung Cancer: Immunohistochemical Markers

Introduction Lung cancer is the leading cause of cancer death in the United States ( ) and NSCLC comprises approximately 85% of lung cancer cases. It is estimated that 25% of patients present with Stage I and II disease ( ) typically managed with surgery with or without adjuvant chemotherapy ( ; ). However, despite having early-stage disease, approximately 50% of these patients will relapse (…

Brain Metastases from Non-Small Cell Lung Cancer: Current Evidence in Management Using Tyrosine Kinase Inhibitor and Whole-Brain Radiation Therapy

Introduction The annual incidence of lung cancer in 2012 in the United States was 226 160 patients (14% of all cancer patients), and an estimated 160 340 patients (28% of cancer mortality) will die of the disease ( ). About 20–44% of patients with lung cancer will develop brain metastases ( ; ). Patients with non-small cell lung cancer (NSCLC) presenting with single or oligometastatic disease can be…

Brain Metastasis from Non-Small Cell Lung Cancer: Use of Epidermal Growth Factor Receptor and HER2 Status for Targeted Therapy

Introduction The most common origins of brain metastases in adults are lung (50–60%) and breast cancers (15–20%) ( ). Lung cancers are divided into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma subtypes. Because SCLCs have a high tendency of brain metastases at first diagnosis, central nervous system (CNS) prophylaxis is the classic standard…

Brain Metastasis in Patients with Non-Small Cell Lung Cancer: Response to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

Introduction The development of brain metastases occurs in up to 44% of patients with advanced non-small cell lung cancer (NSCLC), particularly in patients with adenocarcinoma ( ). Brain metastases are associated with a poor prognosis, with a median overall survival of 4–11 weeks in untreated patients and 4–15 months in treated patients ( ; ). Treatment of brain metastases remains a challenge. The blood–brain barrier is…

Whole-Brain Radiotherapy for Brain Metastases: Is the Therapeutic Window Enlarging?

Introduction Whole-brain radiotherapy (WBRT) has been an integral part of the treatment of brain metastases for the last several decades. It has been shown to improve neurologic symptoms and quality of life, and decreases death from neurologic causes. Since its introduction more than 50 years ago, it has been used for palliative benefit, primary treatment, and adjuvant therapy to both surgical resection and stereotactic radiosurgery (SRS), as…

The Role of Surgical Resection for Metastatic Brain Tumors

Introduction Brain metastases are 10 times more common than any primary brain neoplasm. Approximately 20–40% of patients suffering from systemic cancer develop symptomatic brain metastases, translating into a huge disease burden annually ( ). In adults, lung cancer is the most common source of brain metastases (50–60%), followed by breast cancer (15–20%) and melanoma (5–10%) ( ). The optimal management of brain metastases remains controversial. Whole-brain…

Brain Metastasis from Solid Tumors

Introduction Brain metastasis is common in patients with advanced solid tumors, occurring in roughly 15% of all cancer patients. According to autopsy analyses, the incidence of brain metastasis is as high as 30% in patients with breast cancer, 40% in patients with lung cancer, and 75% in patients with melanoma ( ). With 170 000 new cases diagnosed annually in the United Sates alone, brain metastases are…

Lambert–Eaton Myesthenic Syndrome and Brain Metastasis from Occult Small Cell Lung Carcinoma: A Clinician’s Perspective

Introduction Small cell lung carcinoma (SCLC) is a highly aggressive tumor, with a high proliferative capability, rapid tumor doubling time, and early onset of metastases carrying a poor prognosis. These features make SCLC a systemic disease in most cases, with 70% of SCLC patients presenting with extensive disease (ED) on diagnosis. The median overall survival of treated patients in the ED stage varies between 6 and…

Brain Metastases from Lung Cancer

Introduction Brain metastases from lung cancer represent a significant portion of all brain metastases. Between 10% and 25% of patients with lung cancer have brain metastases at diagnosis, and about 40–50% of all patients with lung cancer will develop brain metastasis during the course of the disease. Some evidence exists to suggest that improved control of locally advanced disease may be associated with increased incidence of…

Brain Metastasis from Small-Cell Lung Cancer with High Levels of Placental Growth Factor

Introduction Small cell lung cancer (SCLC) is the most aggressive histologic subtype of lung cancer, with a strong predilection for metastasizing early. About 10% of patients with SCLC develop brain metastasis at the time of diagnosis, and the majority of these patients will be symptomatic. The progressive growth of metastasis in the brain is often associated with the terminal stage of the disease, and the prognosis…

Brain Metastasis after Prophylactic Cranial Irradiation in Patients with Small Cell Lung Cancer

Introduction Small cell lung cancer (SCLC) accounts for about 15–20% of all lung cancers. It is both chemo- and radiosensitive. The brain is a common site of metastases. Unfortunately, because of the blood–brain barrier, chemotherapy may not be able to achieve a sufficient tumoricidal dose. Some patients achieve a complete response (CR) to treatment in the chest, only to develop brain metastases (BM) later. In 1974,…

Radiation Management of Synchronous Brain Metastases from Non-Small Cell Lung Cancer

Introduction Lung cancer is the leading cause of cancer-related mortality worldwide ( ). The majority of patients with NSCLC present with locally advanced or metastatic disease. The development of brain metastases is a common site of recurrence and spread ( ). The synchronous development of a lung cancer with metastatic disease to the brain without other metastatic foci can frequently occur in routine clinical practice. The…

Intracranial Disease in Patients with Non-Small Cell Lung Cancer: Treatment with Erlotinib

Introduction Lung cancer affects approximately 1.6 million persons a year globally. In the West, it accounts for approximately 10–15% of new cancer cases and 20–30% of cancer deaths ( ). Metastasis to the brain is responsible for death in up to half of cancer patients. Lung cancer is the most frequent primary site of origin, making up 40–50% of cases ( ). Metastasis involving the central…

Bispecific Targeted Toxin DTATEGF Against Metastatic NSCLC Brain Tumors

Introduction Brain metastases affect 25% of patients with systemic cancer and are at least four times more common than primary brain tumors ( ). Nearly half of brain metastases arise from the lung and involve the cerebral hemispheres 80% of the time ( ). Non-small cell lung cancer (NSCLC) constitutes 80% of lung cancer in patients that usually have advanced systemic disease or metastatic spread (…

Brain Metastases from Non-Small Cell Lung Cancer: Clinical Benefits of Erlotinib and Gefitinib

Introduction A 60-year old never-smoker woman presents with left-sided weakness and ataxia due to innumerable metastatic lesions within the brain originating from an advanced adenocarcinoma of the lung. She receives whole brain radiotherapy (WBRT) and systemic chemotherapy and her symptoms temporarily improve. A few months later her disease recurs both clinically and radiographically within the brain. Institution of erlotinib, a small molecule inhibitor of the epidermal…

Solitary Brain Metastasis from Non-Small Cell Lung Cancer: Treatment with Linac-Based Stereotactic Radiosurgery

Introduction Stage IV metastatic disease will be found in approximately 30–40% of patients with non-small cell lung cancer (NSCLC). The brain represents the most common metastatic site for primary lung. The presence of a solitary brain metastasis is a common neurological situation in lung cancer patients ( ). The best treatment approach for solitary brain metastasis is still not well defined. Whether a single brain metastasis…

Metastatic Spread of Lung Cancer to Brain and Liver: Role of CX3CR1

Introduction Lung cancer leads the ranking of cancer-related mortality in both the USA and Europe ( ). Non-small cell lung cancer (NSCLC) shows predominance over small cell histology (SCLC), which accounts for only 15–20% of the incident cases ( ). The biologic behavior of the two histological subgroups is inherently different, with SCLC being characterized by intense proliferative activity, higher propensity to early dissemination and intrinsic…