Clinical Characteristics of Breast Cancers in African‐American Women with Benign Breast Disease: A Comparison to the Surveillance, Epidemiology, and End Results Program

Benign breast disease ( BBD ) is a very common condition, diagnosed in approximately half of all A merican women throughout their lifecourse. White women with BBD are known to be at substantially increased risk of subsequent breast cancer; however, nothing is known about breast cancer characteristics that develop after a BBD diagnosis in A frican‐ A merican women. Here, we compared 109 breast cancers that developed in a population of A frican‐ A merican women with a history of BBD to 10,601 breast cancers that developed in a general population of A frican‐ A merican women whose cancers were recorded by the M etropolitan D etroit C ancer S urveillance S ystem ( MDCSS population). Demographic and clinical characteristics of the BBD population were compared to the MDCSS population, using chi‐squared tests, F isher's exact tests, t ‐tests, and W ilcoxon tests where appropriate. K aplan– M eier curves and Cox regression models were used to examine survival. Women in the BBD population were diagnosed with lower grade (p = 0.02), earlier stage cancers (p = 0.003) that were more likely to be hormone receptor‐positive (p = 0.03) compared to the general metropolitan Detroit A frican‐ A merican population. In situ cancers were more common among women in the BBD cohort (36.7%) compared to the MDCSS population (22.1%, p < 0.001). Overall, women in the BBD population were less likely to die from breast cancer after 10 years of follow‐up (p = 0.05), but this association was not seen when analyses were limited to invasive breast cancers. These results suggest that breast cancers occurring after a BBD diagnosis may have more favorable clinical parameters, but the majority of cancers are still invasive, with survival rates similar to the general A frican‐ A merican population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109284/1/tbj12331.pd

Breast Cancer Presenting as Unilateral Arm Edema

CONTEXT: Symptomatic arm lymphedema as the presenting symptom of invasive breast carcinoma is a rare occurrence. DESIGN: We report a case of invasive breast cancer presenting with unilateral arm swelling. The patient was initially thought to have venous thrombosis. A thorough physical examination and a mammogram revealed the presence of breast cancer and associated subclinical axillary lymphadenopathy. CONCLUSION: Failure to recognize this presentation can lead to misdiagnosis or a significant delay in diagnosis and treatment

Aurora-A Mitotic Kinase Induces Endocrine Resistance through Down-Regulation of ERα Expression in Initially ERα+ Breast Cancer Cells

Development of endocrine resistance during tumor progression represents a major challenge in the management of estrogen receptor alpha (ERα) positive breast tumors and is an area under intense investigation. Although the underlying mechanisms are still poorly understood, many studies point towards the ‘cross-talk’ between ERα and MAPK signaling pathways as a key oncogenic axis responsible for the development of estrogen-independent growth of breast cancer cells that are initially ERα+ and hormone sensitive. In this study we employed a metastatic breast cancer xenograft model harboring constitutive activation of Raf-1 oncogenic signaling to investigate the mechanistic linkage between aberrant MAPK activity and development of endocrine resistance through abrogation of the ERα signaling axis. We demonstrate for the first time the causal role of the Aurora-A mitotic kinase in the development of endocrine resistance through activation of SMAD5 nuclear signaling and down-regulation of ERα expression in initially ERα+ breast cancer cells. This contribution is highly significant for the treatment of endocrine refractory breast carcinomas, because it may lead to the development of novel molecular therapies targeting the Aurora-A/SMAD5 oncogenic axis. We postulate such therapy to result in the selective eradication of endocrine resistant ERαlow/− cancer cells from the bulk tumor with consequent benefits for breast cancer patients

Clinicopathologic Features Associated With Having Four or More Metastatic Axillary Nodes in Breast Cancer Patients With a Positive Sentinel Lymph Node

The survival benefit of a completion axillary lymph node dissection (ALND) in patients after removal of a metastatic sentinel lymph node (SLN) is uncertain and is under study in ongoing clinical trials. The completion ALND remains necessary, however, for the identification of cases with at least four metastatic lymph nodes, in which extended-field locoregional and/or postmastectomy radiation will be recommended. Our goal was evaluate clinicopathologic features that might serve as surrogates for determining which patients with a positive SLN are likely or unlikely to belong to this high-risk subset.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41409/1/10434_2006_Article_9251.pd

Diagnostic utility of snail in metaplastic breast carcinoma

Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer characterized by coexistence of carcinomatous and sarcomatous components. Snail is a nuclear transcription factor incriminated in the transition of epithelial to mesenchymal differentiation of breast cancer. Aberrant Snail expression results in lost expression of the cell adhesion molecule E-cadherin, an event associated with changes in epithelial architecture and invasive growth. We aimed to identify the utility of Snail, and of traditional immunohistochemical markers, in accurate MBC classification and to evaluate clinicopathologic characteristics and outcome

Microenvironmental Influences that Drive Progression from Benign Breast Disease to Invasive Breast Cancer

Invasive breast cancer represents the endpoint of a developmental process that originates in the terminal duct lobular units and is believed to progress through stages of increasing proliferation, atypical hyperplasia, and carcinoma in situ before the cancer acquires invasive and metastatic capabilities. By comparison with invasive breast cancer, which has been studied extensively, the preceding stages of benign breast disease are more poorly understood. Much less is known about the molecular changes underlying benign breast disease development and progression, as well as the transition from in situ into invasive disease. Even less focus has been given to the specific role of stroma in this progression. The reasons for lack of knowledge about these lesions often come from their small size and limited sample availability. More challenges are posed by limitations of the models used to investigate the lesions preceding invasive breast cancer. However, recent studies have identified alterations in stromal cell function that may be critical for disease progression from benign disease to invasive cancer: key functions of myoepithelial cells that maintain tissue structure are lost, while tissue fibroblasts become activated to produce proteases that degrade the extracellular matrix and trigger the invasive cellular phenotype. Gene expression profiling of stromal alterations associated with disease progression has also identified key transcriptional changes that occur early in disease development. In this review, we will summarize recent studies showing how stromal factors can facilitate progression of ductal carcinoma in situ to invasive disease. We also suggest approaches to identify processes that control earlier stages of disease progression

Is Blue Dye Indicated for Sentinel Lymph Node Biopsy in Breast Cancer Patients With a Positive Lymphoscintigram?

The use of isosulfan blue dye in sentinel node biopsy for breast cancer has been questioned because of its risk of allergic reaction. We hypothesized that blue dye could be safely omitted in the subgroup of patients who have evidence of successful sentinel node localization by lymphoscintigraphy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41406/1/10434_2005_Article_6556.pd