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

An optimized five-gene multi-platform predictor of hormone receptor negative and triple negative breast cancer metastatic risk

Abstract Introduction Outcome predictors in use today are prognostic only for hormone receptor-positive (HRpos) breast cancer. Although microarray-derived multigene predictors of hormone receptor-negative (HRneg) and/or triple negative (Tneg) breast cancer recurrence risk are emerging, to date none have been transferred to clinically suitable assay platforms (for example, RT-PCR) or validated against formalin-fixed paraffin-embedded (FFPE) HRneg/Tneg samples. Methods Multiplexed RT-PCR was used to assay two microarray-derived HRneg/Tneg prognostic signatures IR-7 and Buck-4) in a pooled FFPE collection of 139 chemotherapy-naïve HRneg breast cancers. The prognostic value of the RT-PCR measured gene signatures were evaluated as continuous and dichotomous variables, and in conditional risk models incorporating clinical parameters. An optimized five-gene index was derived by evaluating gene combinations from both signatures. Results RT-PCR measured IR-7 and Buck-4 signatures proved prognostic as continuous variables; and conditional risk modeling chose nodal status, the IR-7 signature, and tumor grade as significant predictors of distant recurrence (DR). From the Buck-4 and IR-7 signatures, an optimized five-gene (TNFRSF17, CLIC5, HLA-F, CXCL13, XCL2) predictor was generated, referred to as the Integrated Cytokine Score (ICS) based on its functional pathway linkage through interferon-γ and IL-10. Across all FFPE cases, the ICS was prognostic as either a continuous or dichotomous variable, and conditional risk modeling selected nodal status and ICS as DR predictors. Further dichotomization of node-negative/ICS-low FFPE cases identified a subset of low-grade HRneg tumors with &lt;10% 5-year DR risk. The prognostic value of ICS was reaffirmed in two previously studied microarray assayed cohorts containing 274 node-negative and chemotherapy naive HRneg breast cancers, including 95 Tneg cases where it proved prognostically independent of Tneg molecular subtyping. In additional HRneg/Tneg microarray assayed cohorts, the five-gene ICS also proved prognostic irrespective of primary tumor nodal status and adjuvant chemotherapy intervention. Conclusion We advanced the measurement of two previously reported microarray-derived HRneg/Tneg breast cancer prognostic signatures for use in FFPE samples, and derived an optimized five-gene Integrated Cytokine Score (ICS) with multi-platform capability of predicting metastatic outcome from primary HRneg/Tneg tumors independent of nodal status, adjuvant chemotherapy use, and Tneg molecular subtype

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

Immune cell quantitation in normal breast tissue lobules with and without lobulitis

While the immune microenvironment has been investigated in breast cancers, little is known about its role in non-malignant breast tissues. Here we quantify and localize cellular immune components in normal breast tissue lobules, with and without visible immune infiltrates (lobulitis). Up to ten representative lobules each in eleven normal breast tissue samples were assessed for B cells (CD20), cytotoxic T cells (CD8), helper T cells (CD4), dendritic cells (CD11c), leukocytes (CD45), and monocytes/macrophages (CD68). Using digital image analysis, immune cell densities were measured and compared between lobules with/without lobulitis. 109 lobules in 11 normal breast tissue samples were evaluated; 31 with lobulitis and 78 without. Immune cells showed consistent patterns in all normal samples, predominantly localized to lobules rather than stroma. Regardless of lobulitis status, most lobules demonstrated CD8+, CD11c+, CD45+, and CD68+ cells, with lower densities of CD4+ and CD20+ cells. Both CD11c+ and CD8+ cells were consistently and intimately associated with the basal aspect of lobule epithelium. Significantly higher densities of CD4+, CD8+, CD20+, and CD45+ cells were observed in lobules with lobulitis. In contrast, densities of monocytes/macrophages and dendritic cells did not vary with lobulitis. In normal breast tissue, myeloid and lymphoid cells are present and localized to lobules, with cytotoxic T and dendritic cells directly integrated with epithelium. Lobules with lobulitis have significantly more adaptive immune (B and T) cells, but no increase in dendritic cells or monocytes/macrophages. These findings indicate an active and dynamic mucosal immune system in normal breast tissue

Mammographic breast density and risk of breast cancer in women with atypical hyperplasia: an observational cohort study from the Mayo Clinic Benign Breast Disease (BBD) cohort

BACKGROUND: Atypical hyperplasia (AH) and mammographic breast density (MBD) are established risk factors for breast cancer (BC), but their joint contributions are not well understood. We examine associations of MBD and BC by histologic impression, including AH, in a subcohort of women from the Mayo Clinic Benign Breast Disease Cohort. METHODS: Women with a diagnosis of BBD and mammogram between 1985 and 2001 were eligible. Histologic impression was assessed via pathology review and coded as non-proliferative disease (NP), proliferative disease without atypia (PDWA) and AH. MBD was assessed clinically using parenchymal pattern (PP) or BI-RADS criteria and categorized as low, moderate or high. Percent density (PD) was also available for a subset of women. BC and clinical information were obtained by questionnaires, medical records and the Mayo Clinic Tumor Registry. Women were followed from date of benign biopsy to BC, death or last contact. Standardized incidence ratios (SIRs) compared the observed number of BCs to expected counts. Cox regression estimated multivariate-adjusted MBD hazard ratios. RESULTS: Of the 6271 women included in the study, 1132 (18.0%) had low MBD, 2921 (46.6%) had moderate MBD, and 2218 (35.4%) had high MBD. A total of 3532 women (56.3%) had NP, 2269 (36.2%) had PDWA and 470 (7.5%) had AH. Over a median follow-up of 14.3 years, 528 BCs were observed. The association of MBD and BC risk differed by histologic impression (p-interaction = 0.03), such that there was a strong MBD and BC association among NP (p < 0.001) but non-significant associations for PDWA (p = 0.27) and AH (p = 0.96). MBD and BC associations for AH women were not significant within subsets defined by type of MBD measure (PP vs. BI-RADS), age at biopsy, number of foci of AH, type of AH (lobular vs. ductal) and body mass index, and after adjustment for potential confounding variables. Women with atypia who also had high PD (>50%) demonstrated marginal evidence of increased BC risk (SIR 4.98), but results were not statistically significant. CONCLUSION: We found no evidence of an association between MBD and subsequent BC risk in women with AH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3082-2) contains supplementary material, which is available to authorized users

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