Benign Papilloma of the Breast.
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ABSTRACT:
SUBMITTER: Sadofsky M
PROVIDER: S-EPMC5528917 | biostudies-other | 2017 Jan-Dec
REPOSITORIES: biostudies-other
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Project description:PURPOSE:Human papillomaviruses (HPV) may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i) confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii) evidence of HPV infections in benign breast tissues prior to the development of HPV-positive breast cancer in the same patients, (iii) evidence that HPVs are biologically active and not harmless passengers in breast cancer. METHODS:RNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR) analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active,?the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC). RESULTS:Thirty (3.5%) low-risk and 20 (2.3%) high-risk HPV types were identified in 855 breast cancers from the TCGA database. The high risk types were HPV 18 (48%), HPV 113 (24%), HPV 16 (10%), HPV 52 (10%). Data from the PCR cohort study indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens) followed by HPV 16 (13%). The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens. CONCLUSION:There were four observations of particular interest: (i) confirmation by both NGS and PCR of the presence of high-risk HPV gene sequences in breast cancers, (ii) a correlation between high-risk HPV in benign breast specimens and subsequent HPV-positive breast cancer in the same patient, (iii) HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of HPV E7 proteins), (iv) HPV oncogenic influences may occur early in the development of breast cancer.
| S-EPMC4679879 | biostudies-literature
Project description:Intraductal papillomatous lesions in the breast may be manifestations of different histological types of tumors, including papillomas and intraductal papillary carcinomas. Intraductal papillomas are relatively rare, with an incidence of 2-3%. They are benign tumors that arise from the mammary duct epithelium. We observed a tumor of this type in a 51-year-old woman who had noted bloody discharge from her right nipple. She was referred for breast sonography a few days later.The sonographic examination revealed a dilated duct enclosing a mass, which was surgically removed. Histological examination revealed that the lesion was benign (intraductal papilloma).This case illustrates the role of imaging in confirming clinical diagnoses of papillomatous lesions. Histological confirmation is always necessary, however, to rule out the presence of intraductal papillary carcinoma.
| S-EPMC3558092 | biostudies-literature
Project description:Benign breast diseases constitute a heterogeneous group of lesions arising in the mammary epithelium or in other mammary tissues, and they may also be linked to vascular, inflammatory or traumatic pathologies. Most lesions found in women consulting a physician are benign. Ultrasound (US) diagnostic criteria indicating a benign lesion are described as well as US findings in the most frequent benign breast lesions.
| S-EPMC3558101 | biostudies-literature
Project description:BackgroundHuman papilloma viruses (HPVs) may act early in breast oncogenesis ("hit-and-run" phenomena).MethodsThe authors used immunohistochemistry for the identification of HPV E7 oncogenic protein expression in 32 sets of benign and subsequent breast cancer specimens from the same Australian patients.ResultsHPV E7 oncoprotein was clearly expressed in the nuclei of 23 (72%) of the 32 benign specimens and 20 (62.5%) of the subsequent 32 breast cancer specimens in the same patients. There was no HPV E7 protein expression in seven (30%) of the 23 breast cancer specimens that had prior HPV E7 protein-positive benign breast biopsies in the same patients.ConclusionsThis observation suggests that HPV oncogenic influences occur early in some breast cancers. This finding confirms the previous observations. This early influence of HPVs may be the reason why there is no increase in the prevalence of HPV-associated breast cancer in immunocompromised patients as compared to HPV-associated cervical cancer.
| S-EPMC4676430 | biostudies-literature
Project description:BackgroundMammographic breast density (MBD) and benign breast disease (BBD) are two of the strongest risk factors for breast cancer. Understanding trends in MBD by age and parity in women with BBD is essential to the clinical management and prevention of breast cancer.MethodsUsing data from the Early Determinants of Mammographic Density (EDMD) study, a prospective follow-up study of women born in 1959-1967, we evaluated MBD in 676 women. We used linear regression with generalized estimating equations to examine associations between self-reported BBD and MBD (percent density, dense area, and non-dense area), assessed through a computer-assisted method.ResultsA prior BBD diagnosis (median age at diagnosis 32 years) was reported by 18% of our cohort. The median time from BBD diagnosis to first available study mammogram was 9.4 years (range 1.1-27.6 years). Women with BBD had a 3.44% higher percent MBD (standard error (SE) = 1.56, p-value = 0.03) on their first available mammogram than women without BBD. Compared with parous women without BBD, nulliparous women with BBD and women with a BBD diagnosis prior to first birth had 7-8% higher percent MBD (β = 7.25, SE = 2.43, p-value< 0.01 and β = 7.84, SE = 2.98, p-value = 0.01, respectively), while there was no difference in MBD in women with a BBD diagnosis after the first birth (β = -0.22, SE = 2.40, p-value = 0.93).ConclusionWomen with self-reported BBD had higher mammographic breast density than women without BBD; the association was limited to women with BBD diagnosed before their first birth.
| S-EPMC8074418 | biostudies-literature
Project description:BackgroundAlthough high risk HPVs are associated with an increased risk of prostate cancer it is not known if they have a causal role. The purpose of this study is to investigate the potential role of human papilloma viruses (HPVs) in prostate cancer. The aims are (i) to investigate the presence and confirm the identity of high risk HPVs in benign prostate tissues prior to the development of HPV positive prostate cancer in the same patients, and (ii) to determine if HPVs are biologically active.MethodsWe used polymerase chain reaction (PCR) to identify HPVs in specimens from 52 Australian men with benign prostate biopsies who 1 to 10 years later developed prostate cancer. Immunohistochemistry (IHC) was used to assess the expression of HPV E7 oncoproteins, cytokeratin and prostate specific antigen (PSA). We used RNASeq data from The Cancer Genome Atlas (TCGA) to identify possible HPV RNA sequences in prostate cancer.ResultsHPV screening using standard PCR was conducted on 28 of the 52 sets of benign and later prostate cancers. HPV L1 genes were identified in 13 (46%) benign and 8 (29%) of 28 later prostate cancers in the same patients. HPV E7 genes were identified in 23 (82%) benign and 19 (68%) of 28 subsequent prostate cancers in the same patients. The same HPV types were present in both the benign and subsequent prostate cancers in 9 sets of specimens. HPV type 16 was identified in 15% of benign and 3% of prostate cancers. HPV type 18 was identified in 26% of benign and 16% of prostate cancers. Small numbers of HPV types 45, 47, 76 and 115 were also identified. High confidence RNA-Seq evidence for high risk HPV types 16 and 18 was identified in 12 (2%) of the 502 TCGA prostate cancer transcriptomes. High risk HPV E7 oncoprotein was positively expressed in 23 (82%) of 28 benign prostate specimens but only in 8 (29%) of 28 of the later prostate cancer specimens. This difference is statistically significant (p = 0.001). Prostate specific antigen (PSA) was more highly expressed in 26 (50%) of 52 prostate cancer specimens as compared to prior benign prostate specimens in the same patients.ConclusionsHigh risk HPVs are present in benign prostate tissues prior to the development of HPV positive prostate cancer. There is a significantly higher expression of HPV E7 oncoproteins in benign prostate tissues as compared to late prostate cancer that subsequently developed in the same patients. This observation suggests that HPV oncogenic activity is an early phenomenon in a majority of prostate oncogenesis. TCGA RNA-Seq data suggests that HPV is biologically active in some prostate tumour samples.
| S-EPMC5553674 | biostudies-literature
Project description:BackgroundBenign breast disease and high breast density are prevalent, strong risk factors for breast cancer. Women with both risk factors may be at very high risk.MethodsWe included 42818 women participating in the Breast Cancer Surveillance Consortium who had no prior diagnosis of breast cancer and had undergone at least one benign breast biopsy and mammogram; 1359 women developed incident breast cancer in 6.1 years of follow-up (78.1% invasive, 21.9% ductal carcinoma in situ). We calculated hazard ratios (HRs) using Cox regression analysis. The referent group was women with nonproliferative changes and average density. All P values are two-sided.ResultsBenign breast disease and breast density were independently associated with breast cancer. The combination of atypical hyperplasia and very high density was uncommon (0.6% of biopsies) but was associated with the highest risk for breast cancer (HR = 5.34; 95% confidence interval [CI] = 3.52 to 8.09, P < .001). Proliferative disease without atypia (25.6% of biopsies) was associated with elevated risk that varied little across levels of density: average (HR = 1.37; 95% CI = 1.11 to 1.69, P = .003), high (HR = 2.02; 95% CI = 1.68 to 2.44, P < .001), or very high (HR = 2.05; 95% CI = 1.54 to 2.72, P < .001). Low breast density (4.5% of biopsies) was associated with low risk (HRs <1) for all benign pathology diagnoses.ConclusionsWomen with high breast density and proliferative benign breast disease are at very high risk for future breast cancer. Women with low breast density are at low risk, regardless of their benign pathologic diagnosis.
| S-EPMC3714021 | biostudies-literature
Project description:PurposeWomen with human papilloma virus (HPV)-associated cervical neoplasia have a higher risk of developing breast cancer than the general female population. The purpose of this study was to (i) identify high-risk HPVs in cervical neoplasia and subsequent HPV positive breast cancers which developed in the same patients and (ii) determine if these HPVs were biologically active.MethodsA range of polymerase chain reaction and immunohistochemical techniques were used to conduct a retrospective cohort study of cervical precancers and subsequent breast cancers in the same patients.ResultsThe same high-risk HPV types were identified in both the cervical and breast specimens in 13 (46%) of 28 patients. HPV type 18 was the most prevalent. HPVs appeared to be biologically active as demonstrated by the expression of HPV E7 proteins and the presence of HPV-associated koilocytes. The average age of these patients diagnosed with breast cancer following prior cervical precancer was 51 years, as compared to 60 years for all women with breast cancer (p for difference = 0.001).ConclusionThese findings indicate that high-risk HPVs can be associated with cervical neoplasia and subsequent young age breast cancer. However, these associations are unusual and are a very small proportion of breast cancers. These outcomes confirm and extend the observations of two similar previous studies and offer one explanation for the increased prevalence of serious invasive breast cancer among young women.
| S-EPMC4705232 | biostudies-literature
Project description:Using prospective data from the Early Determinants of Mammographic Density study (United States, 1959-2008, n = 1121), we examined the associations between maternal body size, birth size, and infant and early childhood growth during 3 time periods (0-4 months, 4-12 months, and 1-4 years) and benign breast disease (BBD) using multivariable logistic regression with generalized estimating equations. A total of 197 women (17.6%) reported receiving a diagnosis of BBD by a physician. Higher body mass index at age 7 years was inversely associated with BBD risk. Rapid weight gain from age 1 year to 4 years, defined as an increase of least 2 major percentiles (e.g., 5th, 10th, 25th, 50th, 75th, and 95th) relative to stable growth, defined as remaining within 2 percentiles, was also inversely associated with BBD (odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.23, 1.15). In contrast, rapid weight gain in infancy was positively associated with BBD relative to stable growth (from 0 to 4 months, OR = 1.65, 95% CI: 1.04, 2.62; from 4 to 12 months, 1.85, 95% CI: 0.89, 3.85), independent of birth weight, which was not associated with BBD. Our results suggest that patterns of early-life weight gain are important to BBD risk. Thus, susceptibility to BBD, like susceptibility to breast cancer, might start in early life.
| S-EPMC6736448 | biostudies-literature
Project description:BACKGROUND: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection. METHODS: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins. RESULTS: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs). INTERPRETATION: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.
| S-EPMC2768439 | biostudies-other