Management of breast cancer in elderly individuals: recommendations of the International Society of Geriatric Oncology.

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality in women worldwide. Elderly individuals make up a large part of the breast cancer population, and there are important specific considerations for this population. The International Society of Geriatric Oncology created a task force to assess the available evidence on breast cancer in elderly individuals, and to provide evidence-based recommendations for the diagnosis and treatment of breast cancer in such individuals. A review of the published work was done with the results of a search on Medline for English-language articles published between 1990 and 2007 and of abstracts from key international conferences. Recommendations are given on the topics of screening, surgery, radiotherapy, (neo)adjuvant hormone treatment and chemotherapy, and metastatic disease. Since large randomised trials in elderly patients with breast cancer are scarce, there is little level I evidence for the treatment of such patients. The available evidence was reviewed and synthesised to provide consensus recommendations regarding the care of breast cancer in older adults.

Mechanoregulation of monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells.

The authors have previously shown that arterial wall strain mediates the development of vessel wall inflammation in experimental hypertension. The current studies explore the mechanoregulation of monocyte chemoattractant protein-1 (MCP-1), a potent pro-inflammatory chemokine, by mitogen-activated protein kinases (MAPK) and oxidative stress. Rat aortic smooth muscle (RASM) cells were subjected to cyclic strain on a uniform biaxial strain device. Strain rapidly activated both ERK1/2(MAPK) and p38(MAPK), with peak activation at 5 min. Strain induced a twofold increase in MCP-1 mRNA, which was attenuated by PD 98059, a specific ERK1/2(MAPK) inhibitor, and SB 203580, a specific p38(MAPK) inhibitor. Cyclic strain also increased production of superoxide anion via an NADPH oxidase-dependent mechanism. To assess the potential role of reactive oxygen species in MAPK activation, cells were stretched in the presence of N-acetylcysteine, which had no effect on p38(MAPK) activation, but significantly inhibited ERK1/2(MAPK) activation and MCP-1 expression. In conclusion, redox-sensitive activation of ERK1/2(MAPK) and redox-insensitive activation of p38(MAPK) regulate straininduced MCP-1 expression in RASM cells. These findings define a role for MAPK signal transduction in establishing a pro-inflammatory state in the arterial wall, and thus implicate a potential molecular link between arterial wall strain and atherosclerosis.

Lymphedema following axillary lymph node dissection for breast cancer.

Lymphedema is a relatively common, potentially serious and unpleased complication after axillary lymph node dissection (ALND) for breast cancer. It may be associated with functional, esthetic, and psychological problems, thereby affecting the quality-of-life (QOL) of breast cancer survivors. Objective measurements (preferentially by measuring arm volumes or arm circumferences at predetermined sites) are required to identify lymphedema, but also subjective assessment can help to determine the clinical significance of any volume/circumference differences. Lymphedema per se predisposes to the development of other secondary complications, such as infections of the upper limb, psychological sequelae, development of malignant tumors, alterations of the QOL, etc. The risk of lymphedema is associated with the extent of ALND and the addition of axillary radiation therapy. Treatment involves the application of therapeutic measures of the so-called decongestive lymphatic therapy. Prevention is of key importance to avoid lymphedema formation. The application of the sentinel lymph node biopsy in the management of breast cancer has been associated with a reduced incidence of lymphedema formation.

Effects of hydration on blood rheology.

This study investigated the impact of oral fluid intake on blood rheology of 17 healthy adults following a 12-14 hour overnight fast from food and drink. An oral fluid load of 500 ml was consumed every 30 minutes for 2 hours. Blood viscosity values at shear rates of 1, 10 and 100 s(-1) were reduced (p<0.05 to p<0.01) at 30 and 120 minutes following hydration; however, these differences were not significant after hematocrit correction. With fluid intake, both uncorrected and corrected viscous component of blood viscoelasticity at oscillatory shear rate of 1 s(-1) and at a constant frequency of 2 Hz were reduced (p<0.05 to p<0.001) at all time points as compared to fasting values. The corrected elastic component of blood viscoelasticity increased 90 minutes after hydration (p<0.05). An overnight fast is accompanied by rheological abnormalities that are altered by fluid intake.

Multicentric mammary carcinoma: evidence of monoclonal proliferation.

BACKGROUND: Both the widespread use of screening mammography and emphasis on breast conservation have raised many questions regarding the clinical and therapeutic management of multicentric mammary carcinoma (MMC). MMC has been postulated to be either a clonal proliferation of a single mammary carcinoma or multiple independent synchronous primary tumors in the same breast. The goal of the current study was to evaluate the histologic features and immunohistochemical profile of MMC. We also compared the clinical outcomes of the patients in the current study with stage-matched and treatment-matched groups of patients with unicentric mammary carcinoma. METHODS: The authors studied 32 patients with T1-T2, N0-1, M0 multicentric invasive mammary carcinomas diagnosed between 1983-1988 and treated at The University of Texas M. D. Anderson Cancer Center. The histologic features of each tumor (including tumor type, nuclear grade, presence of in situ carcinoma, pattern of in situ carcinoma, and lymphovascular invasion) were evaluated. The authors performed immunohistochemical analysis of estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, and Ki-67 in 25 cases, including 14 from which > 1 tumor was available to perform comparative immunohistochemical analysis. The clinical parameters of each case were compared with those of the unicentric breast carcinoma controls. RESULTS: The median age of the patients with MMC was 45 years (range, 28-69 years). Twelve patients had a family history of breast carcinoma (37.5%). The maximum tumor dimension ranged from 0.2-3.2 cm in the index lesion (median, 2.0 cm) and 0.1-2.5 cm in the second lesion (median, 0.9 cm). Twelve patients were clinically classified as having Stage I disease and 20 patients were considered to have Stage II disease at the time of presentation. Follow-up data were available for all the patients and follow-up ranged from 4.5-16 years (median, 6 years). The disease-free survival was 84% at 5 years and 73% at 10 years in the MMC patients and 78% and 70%, respectively, in patients with unicentric breast carcinoma (P = 0.4368). Histologically, 24 of the multicentric tumors were found to be infiltrating ductal tumors and 8 were found to be infiltrating lobular carcinomas. The nipple was involved in 10 cases. The histology of the multicentric invasive tumor was nearly identical in 31 cases (97%). Approximately 72% of the cases had in situ carcinoma in both tumors and 44% had lymphovascular invasion. Comparative immunohistochemical analysis of separate tumors was equivalent with regard to ER, PR, and HER-2/neu. The quantitative immunohistochemical staining for the proliferative marker Ki-67 differed between tumors in two cases. CONCLUSIONS: The near-identical morphologic and immunohistochemical patterns in the MMC cases in the current study support the hypothesis that early-stage synchronous tumors are a clonal proliferation of a single mammary carcinoma. Furthermore, the results of the current study support evaluating prognostic markers in only one tumor per MMC patient. There was no appreciable difference in the disease-free survival of patients with unicentric and multicentric breast carcinoma.