Papel de los bisfosfonatos en el tratamiento adyuvante del cáncer de mama / The role of bisphosphonates of adjuvant therapy in breast cancer

El cáncer de mama es la neoplasia maligna más frecuente en las mujeres. El hueso es la localización más común de diseminación mestastásica del cáncer de mama precoz y es además la causa de dolor, fracturas e hipercalcemia en estas mujeres. Esta diseminación depende de la liberación de sustancias osteolíticas por parte de las células tumorales. La consecuente activación de los osteoclastos produce, a su vez, la liberación de factores de crecimiento que estimulan la proliferación de las células neoplásicas. Los bisfosfonatos, agentes antiosteolíticos, han demostrado su capacidad para reducir la progresión de metástasis óseas ya establecida. Pero éste no es el único mecanismo por el que los bisfosfonatos ejercen su acción antitumoral. Su capacidad de interferir en la vía de la angiogénesis tumoral o de modular el sistema inmunitario son algunos de los mecanismos que han llevado al desarrollo de estudios con el objetivo de establecer su papel como tratamiento adyuvante adicional en mujeres con cáncer de mama temprano. El bisfosfonato oral clodronato (1,600mg/día) es eficaz para el tratamiento de pacientes con metástasis óseas. Cuando se usa como tratamiento adyuvante durante 2 años en mujeres operadas de cáncer de mama precoz demuestra una reducción significativa del riesgo de metástasis óseas durante este período, con una significativa reducción de la mortalidad. Este beneficio, junto con su baja toxicidad y seguridad, apoyan su uso como tratamiento adyuvante adicional en mujeres con cáncer de mama precoz. El zoledronato, un potente bisfosfonato nitrogenado de tercera generación y uso parenteral, ha demostrado mantener o incluso mejorar la densidad mineral ósea en mujeres con cáncer de mama precoz en tratamiento hormonal adyuvante, así como en mujeres posmenopáusicas con pérdidas de masa ósea. Estudios más recientes llevados a cabo con este bisfosfonato en el contexto de la (neo)adyuvancia del cáncer de mama precoz otorgan al zoledronato un beneficio en la mejoría de la supervivencia libre de recaída, una reducción de la mortalidad y efecto antitumoral directo basado en la capacidad de inducir regresión del tamaño tumoral y mejoría de la tasa de respuestas patológicas (AU)

Breast cancer is the most common neoplasm in women. Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. Biphosphonates, antiosteolytic agents, have been shown to reduce the progression of established bone metastases. Emerging evidence suggests that biphosphonates also have antitumor and antimetastatic properties, including the inhibition of angiogenesis, tumor-cell invasion, and adhesion in bone; the induction of apoptosis; antitumor sinergy with cytotoxic chemotherapy; and immunomodulatory effects through induction of γ/δ T cells. These findings were the background and rationale for ongoing clinical trials, in order to establish their role as a part of adjuvant treatment for early breast cancer. The oral biphosphonate clodronate (1600mg/d) is effective in patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for two years, clodronate has been reported to reduce the risk of bone metastases during a 2-year study period with a significant reduction in mortality. This benefit supports its use as additional adjuvant therapy for patients with operable breast cancer. Zoledronic acid, a potent nitrogen-containing biphosphonate, has been shown to maintain or increase bone mineral density (BMD) in premenopausal women with early-stage breast cancer receiving adjuvant hormone therapies as well as healthy postmenopausal women with low BMD. Recent large clinical trials with biphosphonates in the (neo)adjuvant setting for early-breast cancer, demonstrate an improvement of disease-free and overall survival as well as increased pathologic rate responses (AU)

[The role of bisphosphonates of adjuvant therapy in breast cancer]. / Papel de los bisfosfonatos en el tratamiento adyuvante del cáncer de mama.

Breast cancer is the most common neoplasm in women. Bone is the most common site of metastatic spread from primary operable breast cancer, causing pain, fractures and hypercalcemia. This spread depends on the release of osteolytic substances by the cancer cells. The osteoclasts also release growth factors that can act back on the cancer cells to activate growth. Biphosphonates, antiosteolytic agents, have been shown to reduce the progression of established bone metastases. Emerging evidence suggests that biphosphonates also have antitumor and antimetastatic properties, including the inhibition of angiogenesis, tumor-cell invasion, and adhesion in bone; the induction of apoptosis; antitumor sinergy with cytotoxic chemotherapy; and immunomodulatory effects through induction of γ/δ T cells. These findings were the background and rationale for ongoing clinical trials, in order to establish their role as a part of adjuvant treatment for early breast cancer. The oral biphosphonate clodronate (1600mg/d) is effective in patients with bone metastases. When used as adjuvant therapy, given to patients with operable breast cancer for two years, clodronate has been reported to reduce the risk of bone metastases during a 2-year study period with a significant reduction in mortality. This benefit supports its use as additional adjuvant therapy for patients with operable breast cancer. Zoledronic acid, a potent nitrogen-containing biphosphonate, has been shown to maintain or increase bone mineral density (BMD) in premenopausal women with early-stage breast cancer receiving adjuvant hormone therapies as well as healthy postmenopausal women with low BMD. Recent large clinical trials with biphosphonates in the (neo)adjuvant setting for early-breast cancer, demonstrate an improvement of disease-free and overall survival as well as increased pathologic rate responses.

Hepatoid adenocarcinoma of the stomach - a different histology for not so different gastric adenocarcinoma: a case report.

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.