Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.
Surgical repair of hip fractures within the first 48 hours was associated with better health outcomes in a nationally representative sample, as observed in an acute care facility, irrespective of comorbid conditions.
A retrospective study was performed to document the uptake and extent of surgical intervention in patients with a known mutation in the BRCA1/2 genes and associated outcomes. Data were collected retrospectively on BRCA-positive patients with and without cancer at the time of genetic testing. Our findings were compared to those published in the current literature. Of patients with cancer at testing, 61% chose bilateral mastectomies. Of patients without cancer, 54% chose risk-reducing surgery (RRS) including risk-reducing mastectomy (RRM), risk-reducing salpingo-oophorectomy (RRSO), or both. Time to surgery was significantly shorter to RRSO than to RRM. The literature suggests and our data support that acceptance of RRM in the BRCA-positive population has gradually increased over time. Consistently high rates of RRSO uptake and short intervals from time-of-testing to RRSO demonstrate that RRSO is still more acceptable to this population than RRM.
Patient: Female, 67Final Diagnosis: Breast angiosarcomaSymptoms: Skin lesionMedication: —Clinical Procedure: SurgerySpecialty: OncologyObjective:Unusual clinical courseBackground:Radiation-associated breast angiosarcoma is a rare clinical entity that is thought to be increasing in incidence.Case Report:Here we present the case of a 67-year-old female with a history of left breast invasive ductal carcinoma who received breast conserving surgery and radiation therapy eight years ago. She then presented with a painless mild skin discoloration of the left breast that had been present for over one year. Mammograms and ultra-sounds were normal. A punch biopsy and a subsequent excisional biopsy revealed the diagnosis of angiosarcoma. The patient was treated with mastectomy and had no subsequent recurrences.Conclusions:The long-term clinical surveillance for all patients who receive breast conservation surgery is recommended and a high degree of suspicion should be exercised in view of potential atypical presentations of this disease.
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