Hanne M. Jensen

Mammographic densities and the prevalence and incidence of histological types of benign breast disease

There is now a large amount of evidence indicating that women with extensive areas of mammographic densities are 4–6 times more likely to develop breast cancer than those with little or no density in the mammogram. We have examined one potential biological explanation for this association by estimating the incidence of various histological types of benign breast disease in relation to mammographic density. We studied the large cohort of women taking part in the National Breast Screening Study (NBSS), a randomized trial of screening with mammography. Mammograms from subjects with biopsies (n =423) and from a comparison group of subjects randomly selected from the NBSS (n = 465) were included. Histological slides from biopsied subjects (n = 353) were classified independently by the pathologists of the NBSS and by a review pathologist (H.M.J.). Mammographic density in more than 75% of the breast area was associated with an increased risk of incidence of hyperplasia without atypia, and of atypical hyperplasia and/or carcinoma in situ. The classifications of the review pathologist showed that, compared to women with no density, the relative risk of incident lesions for women with density in more than 75% of breast was 13.85 (95% CI 2.65–72.49) for hyperplasia, and 9.23 (95% CI 1.66–51.48) for atypical hyperplasia and/or carcinoma in situ. These findings suggest that the association between extensive mammographic density and breast cancer risk may, at least in part, be attributable to biological processes in the breast that give rise to these histological features that are known to be related to breast cancer risk.

Norovirus binds to blood group A-like antigens in oyster gastrointestinal cells

Aims:  To determine if histo‐blood group antigens (HBGA) present in oyster gastrointestinal (GI) cells mediate accumulation of human noroviruses (NoV) in oyster GI cells.

Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control Study

Background Age, reproductive history, hormones, genetics, and lifestyle are known risk factors for breast cancer, but the agents that initiate cellular changes from normal to malignant are not understood. We previously detected bovine leukemia virus (BLV), a common oncogenic virus of cattle, in the breast epithelium of humans. The objective of this study was to determine whether the presence of BLV DNA in human mammary epithelium is associated with breast cancer. Methods This was a case-control study of archival formalin fixed paraffin embedded breast tissues from 239 donors, received 2002–2008 from the Cooperative Human Tissue Network. Case definition as breast cancer versus normal (women with no history of breast cancer) was established through medical records and examination of tissues by an anatomical pathologist. Breast exposure to BLV was determined by in situ-PCR detection of a biomarker, BLV DNA, localized within mammary epithelium. Results The frequency of BLV DNA in mammary epithelium from women with breast cancer (59%) was significantly higher than in normal controls (29%) (multiply- adjusted odds ratio = 3.07, confidence interval = 1.66–5.69, p = .0004, attributable risk = 37%). In women with premalignant breast changes the frequency of BLV DNA was intermediate (38%) between that of women with breast cancer and normal controls (p for trend < .001). Conclusions Among the specimens in this study, the presence of amplified BLV DNA was significantly associated with breast cancer. The odds ratio magnitude was comparable to those of well-established breast cancer risk factors related to reproductive history, hormones, and lifestyle and was exceeded only by risk factors related to genetics (familial breast cancer), high dose ionizing radiation, and age. These findings have the potential for primary and secondary prevention of breast cancer.

Bovine Leukemia Virus DNA in Human Breast Tissue

Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease.

Preliminary Results for Shear Wave Speed of Sound and Attenuation Coefficients from Excised Specimens of Human Breast Tissue

A pilot study involving 53 specimens of excised human female breast tissue was performed to provide preliminary estimates of the acoustic shear wave speed of sound and linear attenuation coefficient associated with high risk for development of invasive breast cancer. The measured shear wave properties were studied as a function of: 1. whether the tissue was presented as a 2.0 to 4.0 gram mass biopsy sample or a 2.0 to 4.0 gram mass subsample taken from a larger mastectomy source; 2. the time post-excision prior to shear wave characterization; 3. the risk factor associated with the number and types of lesions found in the specimen; and 4. the percent by volume of fat or collagen present in the sample. The shear speed of sound was found to range between 20 and 900 m/s with a tendency for lower speeds as a function of time post excision. The results for shear attenuation coefficients ranged from 300 to 9000 cm-1 and did not show a marked time dependence. Average results from mastectomy specimens differed from those for biopsies, but the difference may have been due to variations in tissue composition and time post excision before shear wave characterization.

Preliminary investigation of ultrasound scattering analysis to identify women at risk for later invasive cancer. I: Motivation and experimental technique for characterization of isolated breast tissue lobules

A new experimental technique is described that allows the characterization of the angle-dependent ultrasonic scattering properties of isolated breast tissue lobules. A review of breast tissue micro-architecture is presented as background material. Measured estimates of the scatter angle-dependent differential scatter cross-sections (DSC) from 31 excised lobules (14 cancer in situ, 17 noncancer) were examined, and dominant trends described by statistical factors. Three factors were extracted, using principal component factor analysis, which collectively accounted for over 70% of the scatter angle-dependent variation exhibited by the measured data.

TRALI is due to pulmonary venule damage from leucocytes with cholesterol crystal formation

Background  There are two presumed mechanisms for the pulmonary oedema in transfusion‐related acute lung injury (TRALI). One is antibodies to leucocytes while the other is biologically active lipids. We evaluated the vascular injury due to the former.

Neutrophils contain cholesterol crystals in transfusion-related acute lung injury (TRALI).

OBJECTIVES Intracellular components of transfusion-related acute lung injury (TRALI) were investigated by transmission electron microscopy. METHODS The lungs from 2 fatal TRALI cases and 2 controls, previously studied by scanning electron microscopy, were studied by transmission electron microscopy. Morphologic data by light and phase microscopy, along with scanning and transmission electron microscopic observations, were collated. RESULTS The 2 fatal TRALI cases exhibited dense laminated material within capillaries and postcapillary venules, similar to material identified within their neutrophils when viewed by transmission electron microscopy. This material polarized light and is presumed to be cholesterol crystals. CONCLUSIONS The damage to the pulmonary vascular endothelium in TRALI is related to formation of cholesterol crystals originating within neutrophils.

Preliminary investigation of ultrasound scattering analysis to identify women at risk for later invasive cancer. II: Extraction of dominant scattering angle-dependent trends from excised breast tissue

Normalized estimates of the scattering angle-dependent differential scattering cross-section (DSC) at 1.0 MHz were measured from 278 samples of excised breast tissue taken from 66 women. A comparison of results for samples that contained tissue structures previously associated with an increased probability of developing breast cancer to those that did not contain high-risk structures showed that the average magnitude of DSC estimates was insufficient to identify samples with high-risk lesions. Principal component factor analysis (PCFA) was applied to extract scattering angle-dependent trends common to the entire data base. The normalized estimates of the measured DSCs (NDSC) from tissue samples are compared to estimates previously obtained from isolated breast tissue lobules as well as with results from the PCFA. Results are presented that indicate that the dominant angle-dependent trends in the NDSC results are independent of the age of the patient and are similar to trends extracted from isolated breast tissue lobules. The breast tissue structure common to all of these specimens is the terminal duct.

Abstract 892: Survey of human cancer tissues for the presence of bovine leukemia virus

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Bovine leukemia virus (BLV) is an oncogenic retrovirus that causes B cell leukemia/lymphoma in 5% of infected cattle. Infection is widespread in the USA: 24% of beef herds, 84% of dairy herds, and 100% of large dairy operations. BLV has been detected in T cells, B cells, endothelium, and mammary epithelium, and infected cells may be present in the blood and milk of cattle. Previously we found IgG antibodies to BLV in 39% of humans sampled, and BLV-related DNA in 60% (67/112) of malignant human breast tissues. Presence of BLV-related DNA in human mammary epithelium was significantly associated with breast cancer risk (odds ratio = 3.4, confidence interval = 1.77-6.44; P≪ .0002). The purpose of this study was to test other types of human cancers for BLV-related DNA as a first step in exploring whether BLV might be involved in malignancies of tissues other than breast. Specimens were surgical pathology archival material collected from 1992-2003. We performed PCR-in-situ hybridization (PCR-ISH) on formalin-fixed tissue sections, targeting the highly conserved tax region, which codes for the oncogenic protein of BLV. This method is not subject to molecular contamination, and can localize the signal to a particular cell type in the intact tissue. Our survey included the following malignancies: stomach, colon, pancreas, prostate, seminoma, ovary, endometrium, sarcoma (1 liposarcoma, 3 fibrosarcoma, 4 fibrohistiocytoma, 1 Ewing sarcoma), lymphoma (10 B cell, 2 T cell, 3 Hodgkin), squamous cell skin carcinoma, lung, thyroid, and brain (3 astrocytoma, 4 meningioma, 3 glioblastoma). BLV-related amplicons were detected in the following cancer types: stomach (5/10), colon (1/11), brain (2/10 [1 astrocytoma and 1 glioblastoma]), lymphoma (1/15 [T cell lymphoma]), sarcoma (1/9 [poorly differentiated high grade sarcoma]), and squamous cell skin carcinoma (2/10). No tissue type we tested showed a frequency of BLV-related DNA as great as we previously detected in breast cancer (60%). Sample sizes in this pilot survey were too small to provide an accurate estimate of overall frequency in the population or to make any conclusions about the association of BLV-related DNA with the malignancies studied. However, the data do provide some interesting leads for further research with an increased number of specimens and normal control tissue, especially for the cancer types exhibiting at least one positive specimen. This research was supported by a seed grant to HM Jensen from the Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 892. doi:10.1158/1538-7445.AM2011-892