Breast cancer surgery during the Covid-19 pandemic: a monocentre experience from the Regina Elena National Cancer Institute of Rome.

The Covid-19 pandemic has challenged hard the national health systems worldwide. According to the national policy issued in March 2020 in response to the evolving Covid-19 pandemic, several hospitals were re-configured as Covid-19 centers and elective surgery procedures were rescheduled according to the most recent recommendations. In addition, Covid-19 protected cancer hubs were established, including the Regina Elena National Cancer Institute of Rome, Central Italy. At our Institute, the Breast Surgery Department continued working under the sign of a multidisciplinary approach. The number of professional figures involved in case evaluation was reduced to a minimum and interactions took place in the full respect of the required safety measures. Treatments for benign disease, pure prophylactic surgery and elective reconstructive procedures were all postponed and priority was assigned to the histologically-proven malignant breast tumors and highly suspicious lesions. From March 15th though April 30th 2020, we treated a total of 79 patients. This number is fully consistent with the average quantitative standards reached by our Department under ordinary circumstances. Patients were mostly discharged the day after surgery and none was readmitted due to surgery-related late complications. More generally, post-operative complications rates were unexpectedly low, particularly in light of the relatively high number of reconstructive procedures performed in this emergency situation. A strict follow up was performed based on the close contact with the surgical staff by telephone, messaging apps and telemedicine.Patients ascertainment for their Covid-19 status prior to hospital admission and hospital discharge allowed to maintain the "no-Covid-19" status at our Institution. In addition, during the aforementioned time window, none of the care providers developed SARS-CoV-2 infection or disease, as shown by the results of anti-SARS-CoV-2 immunoglobulin M and G profiling. In conclusions, elective breast cancer surgery procedures were successfully performed in a lockdown situation due to a novel viral pandemic. The well-coordinated regional and hospital efforts in terms of medical resource re-allocation and definition of clinical priorities allowed to maintain high quality standards of breast cancer care while ensuring safety to the cancer patients and care providers involved.

Prevalence of Epstein-Barr virus (EBV) in Iranian Breast Carcinoma Patients.

INTRODUCTION: Breast cancer (BC) is the most common malignancy affecting females worldwide. Various risk factors play a role in the developing of BC. Infectious agents like viruses have been proposed for this cancer and Epstein-Barr virus (EBV) is a widely researched candidate virus. This study detects the presence of EBV-DNA in breast cancer patients. METHODS: The study was conducted on 59 formalin-fixed paraffin-embedded (FFPE) tissue blocks samples of women with breast carcinoma and 11 non-neoplastic breast controls. The DNA was extracted for all the samples. Then detection of EBNA1 EBV was done by polymerase chain reaction (PCR). RESULTS: EBV was detected in 6.7% (4/59) of patients while all breast control samples were negative. All patients with positive EBV-DNA were high tumor grades (II, and III). Also, they had a low level of educations. CONCLUSIONS: According to our findings, it can be suggested that EBV may have a potential role in breast cancer development. However, this study provides substantial but not conclusive evidence for the involvement of viruses in BC disease development. Therefore, future investigations are needed to elucidate the exact role of EBV in breast cancer.
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Human Cytomegalovirus DNA among Women with Breast Cancer.

Breast cancer is the most common cause of death among women worldwide. Although there are many known risk factors in breast cancer development, infectious diseases have appeared as one of the important key to contribute to carcinogenesis formation. The effects of Human Cytomegalovirus (HCMV) on women with breast cancer has been recently studied and reported. To contribute to this research trend, this study was conducted to evaluate the association between HCMV and the women with breast cancer. Objective: This experiment aimed to evaluate HCMV DNA in women with breast cancer in Ahvaz city, Iran. Materials and Methods: A total of 37 formalin fixed paraffin embedded tissues of the patients with ductal breast carcinoma and 35 paraffin embedded tissues of the patients with fibro adenoma as control group were collected. The deparaffinization of all the samples were carried out and the DNA was extracted. Initially, the PCR test was carried out to detect beta ­globulin DNA as an internal control. For those samples positive for beta ­globulin DNA, Polymerase Chain reaction (PCR) was used to detect HCMV for the tests and control samples. Results: Among 37 ductal breast carcinoma, 20 (54.04%) cases were proved positive for HCMV DNA by PCR. While among the 35 control group (fibroadenoma), 10 (28.57%) cases were positive for HCMV DNA (P >0.028). The prevalences of HCMV DNA among the age groups 30-39, 40-49 and >50 years were 7 (72.22%), 9 (69.23%), 4 (57.14%), respectively (P=0.066). A high frequency of HCMV DNA was detected in tumor grade III, 13/18 (58.33%) compared with tumor grade II, 7/19 (36.84%) (p=0.044). A high frequency of 16/24 (66.66%) of HCMV DNA was found in invasive ductal breast cancer compared with 4/13 (30.76%) HCMV DNA in situ (P<0.028). Conclusion: A high prevalence of 54.05% HCMV was found among the patients with ductal carcinoma. The percentages of the high prevalence of HCMV among age group (40-49) years, tumors grades, and invasive stage were (69.23%), (58.33%), (66.66%), respectively. Further study of HCMV in the latency phase in patients with ductal carcinoma would be necessary to extend our knowledge.

Frequency of Epstein­Barr Virus DNA in Formalin-Fixed Paraffin-Embedded Tissue of Patients with Ductal Breast Carcinoma

Background: Ductal carcinoma is one of the most common breast cancer (BrC) among the women in the world. Several factors may involve in establishment of breast cancer. The role of viral infections have been investigated in BrC, Among them the association of Epstein Barr virus have been reported in the patients with breast cancer type ductal carcinoma. Thus this study was conducted to evaluate the rate of Epstein Barr virus in women with breast cancer type ductal carcinoma. Material and methods: A total of 72 formalin-fixed paraffin-embedded tissue blocks samples were collected from 37 (51.38%) women with breast cancer type ductal carcinoma and 35 (48.61%) samples of breast with fibro adenoma as control group. The DNA was extracted for all the samples. The detection of EBNA 3C EBV DNA was done by nested PCR. The results of positive were sequenced to confirm PCR product and determine EBV genotypes. Results: About 10/37 (27.02%) samples of ductal breast carcinoma were showed positive for EBNA 3C EBV DNA while 4/35 (11.42%) of fibro adenoma were positive for EBNA 3C EBV DNA (p= 0.095). Randomly 7 PCR products were sequenced and the results of sequencing EBNA 3C shows, the detected EBVDNA were type 1 EBV type. Conclusion: This study shows high prevalence of 27.02% EBV DNA type 1 was found in formalin-fixed paraffin-embedded tissue of Patients with ductal breast carcinoma. The outcomes of this study suggesting that EBV might have a significant role in breast cancer in Ahvaz city, south west region of Iran. However the expression of EBV oncoproteins ,EBNA1, LMP1, and LMP2 require to be determined with ductal carcinoma cells. About 72.97% breast samples showed negative for EBVDNA. The role other viruses including Human cytomegalovirus, papilloma viruses and Merkel viruses are required to be investigated in further studies.

[Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular profile in a population of West Algeria]. / Virus d'Epstein-Barr et carcinomes mammaires invasifs : EBNA, EBER et profil moléculaire dans une population de l'ouest algérien.

Breast cancer is the common malignancy that affects women worldwide, but conventional risk factors account for only a small proportion of these cases. A possible viral etiology for breast cancer has been proposed and Epstein-Barr virus (EBV) is a widely studied candidate virus. The objective of this study is to determine the association of EBV infection with infiltrating ductal carcinomas (IDC). This descriptive study was carried out in the laboratory of developmental biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the clinicopathological characteristics of the population. Of the 23 cases of IDC, we implemented the techniques Elisa, immunohistochemistry and in situ hybridization. To determine the serological profile, overexpression of onco-proteins EBNA-1, HER2, the mitotic index Ki67 and detection of the presence of the viral genome. The mean age is 57.40±4, SBR II predominates with 70%, pN+ (27%), RE+ (58%), RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1 P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79 serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile (p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in the tumors 43% representing an inverse relationship with the overexpression of Ki67 and a positive relationship with the overexpression of HER2. In our study we found an association with the presence of the EBV virus and the IDC studied.

Bovine leukemia virus linked to breast cancer but not coinfection with human papillomavirus: Case-control study of women in Texas.

BACKGROUND: Bovine leukemia virus (BLV) and human papillomavirus (HPV) were previously identified in human breast tissue and have been associated with breast cancer in independent studies. The objective of the current study was to test for the presence of BLV and HPV in the same breast tissue specimens to determine whether the viruses were associated with breast cancer either singly or together. METHODS: Archival formalin-fixed paraffin-embedded breast tissue sections from 216 women were received from The University of Texas MD Anderson Cancer Center along with patient diagnosis. In situ polymerase chain reaction and/or DNA hybridization methods were used to detect targeted DNA segments of BLV and HPV. Standard statistical methods were used to calculate age-adjusted odds ratios, attributable risk, and P values for the trend related to the association between presence of a virus and a diagnosis of breast disease. RESULTS: Women diagnosed with breast cancer were significantly more likely to have BLV DNA in their breast tissue compared with women with benign diagnoses and no history of breast cancer. Women with breast pathology classified as premalignant and no history of breast cancer also were found to have an elevated risk of harboring BLV DNA in their breast tissue. HPV status was not associated with malignancy, premalignant breast disease, or the presence of BLV in the breast tissues. CONCLUSIONS: The data from the current study supported previous findings of a significant association between BLV DNA in breast tissue and a diagnosis of breast cancer, but did not demonstrate oncogenic strains of HPV associated with breast cancer or the presence of BLV DNA in breast tissue. The authors believe the findings of the current study contribute to overall knowledge regarding a possible causal role for viruses in human breast cancer. Cancer 2018;124:1342-9. © 2017 American Cancer Society.

Almost Complete Lack of Human Cytomegalovirus and Human papillomaviruses Genome in Benign and Malignant Breast Lesions in Shiraz, Southwest of Iran

Breast cancer ranks as the most common cancer among women worldwide. There have been controversial reports regarding contributions of human papillomaviruses (HPVs) and human cytomegalovirus (HCMV) to its development. The aim of this study was to determine the frequency of HPV and HCMV positivity in benign and malignant breast tumors. Materials and Methods: Formalin fixed paraffin-embedded tissue specimens of 150 breast cancers (invasive ductal and lobular carcinomas) and 150 non-malignant breast lesions (fibroadenomas, fibrocystic disease and adenosis) were examined. All samples were first deparafinized then subjected to commercial DNA extraction. The ß-globin gene fragment was amplified using polymerase chain reaction (PCR) to confirm the quality of extracted DNA. The presence of HPV and HCMV genomic DNA was determined using PCR and Real time PCR techniques, respectively. Results: The mean ages of the test and control groups were 35.2 and 45 years, respectively. For HCMV, none of the malignant lesions were positive and only 2 of the 150 benign samples demonstrated presence of the virus. No HPV genomic DNA was found in either malignant or benign cases. Conclusion: The results of this study indicated no relationship between HCMV or HPV infection with breast cancer development. Whether investigations in larger populations with longer follow-up might demonstrate any role remains unclear.

Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast.

BACKGROUND AND AIMS: The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH). METHODS: One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC). RESULTS: HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731). CONCLUSIONS: HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study.

A new immunization and treatment strategy for mouse mammary tumor virus (MMTV) associated cancers.

Mouse Mammary Tumor Virus (MMTV) causes mammary carcinoma or lymphoma in mice. An increasing body of evidence in recent years supports its involvement also in human sporadic breast cancer. It is thus of importance to develop new strategies to impair the development, growth and metastasis of MMTV-associated cancers. The signal peptide of the envelope precursor protein of this virus: MMTV-p14 (p14) is an excellent target for such strategies, due to unique characteristics distinct from its regular endoplasmic reticulum targeting function. These include cell surface expression in: murine cancer cells that harbor the virus, human breast cancer (MCF-7) cells that ectopically express p14, as well as cultured human cells derived from an invasive ductal breast carcinoma positive for MMTV sequences. These findings support its use in signal peptide-based immune targeting. Indeed, priming and boosting mice with p14 elicits a specific anti-signal peptide immune response sufficient for protective vaccination against MMTV-associated tumors. Furthermore, passive immunization using a combination of anti-p14 monoclonal antibodies or the transfer of T-cells from immunized mice (Adoptive Cell Transfer) is also therapeutically effective. With reports demonstrating involvement of MMTV in human breast cancer, we propose the immune-mediated targeting of p14 as a strategy for prevention, treatment and diagnosis of MMTV-associated cancers.

Inflammatory and Non-inflammatory Breast Cancer: A Potential Role for Detection of Multiple Viral DNAs in Disease Progression.

BACKGROUND: Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. Multiple viral infections in IBC tissues were found to be associated with disease pathogenesis. OBJECTIVE: The aim of the present study was to correlate the incidence of viral DNA with breast cancer progression. MATERIALS AND METHODS: Overall, 135 women diagnosed with breast cancer were enrolled in this study. Using polymerase chain reaction and sequencing assays, we determined the incidence of human papillomavirus types 16 and 18 (HPV-16 and -18), human cytomegalovirus (HCMV), Epstein-Barr virus, human herpes simplex virus type 1 and 2, and human herpes virus type 8 (HHV-8) in breast carcinoma tissue biopsies. We also assessed the expression of the cell proliferation marker Ki-67 by immunohistochemistry in association with the incidence of viral DNA. RESULTS: HCMV and HPV-16 were the most detected viral DNAs in breast carcinoma tissues; however, the frequency of HCMV and HHV-8 DNA were significantly higher in IBC than non-IBC tissues. Moreover, the prevalence of multiple viral DNAs was higher in IBC than non-IBC tissues. The incidence of multiple viral DNAs positively correlates with tumor size and number of metastatic lymph nodes in both non-IBC and IBC patients. The expression of Ki-67 was found to be significantly higher in both non-IBC and IBC tissues in which multiple viral DNAs were detected. CONCLUSIONS: The incidence of multiple viral DNAs in IBC tissues was higher compared with non-IBC tissues. The present results suggest the possibility of a functional relationship between the presence of multiple viral DNAs and disease pathogenesis.

Evaluation Frequency of Merkel Cell Polyoma, Epstein-Barr and Mouse Mammary Tumor Viruses in Patients with Breast Cancer in Kerman, Southeast of Iran.

Breast cancer is the most common cancer among women worldwide. Roles of the Epstein-Barr, Merkel cell polyoma and mouse mammary tumor viruses in breast carcinogenesis are still controversial although any relationship would clearly be important for breast cancer etiology, early detection and prevention. In the present study associations between EBV, MMTV and Merkel cell polyoma virus and breast cancer in 100 Iranian patients were evaluated using paraffin-embedded tissues. EBER RNA and expression of p53 and large T antigen were evaluated by real time PCR and CD34, p63, HER2, PR and ER markers were studied by immunohistochemistry. EBV was detected in 8/100 (8%), MMTV in 12/100 (12%), MPy in 3/100 (3%) and EBER RNA in 18/100 (18%) cases. None of the control samples demonstrated any of the viruses. p53 was suppressed in EBV, MPy and MMTV positive samples. The large T antigen rate was raised in MPy positive samples. Our results showed that EBV, MMTV and the Merkel cell polyoma virus are foundwith some proportion of breast cancers in our patients, suggesting that these viruses might have a significant role in breast cancer in Kerman, southeast of Iran.

Epstein-Barr virus infection is equally distributed across the invasive ductal and invasive lobular forms of breast cancer.

The role of Epstein-Barr virus (EBV) in the pathogenesis of breast cancer is still unclear, although a growing body of evidence supports a link. The aim of this study was to investigate if EBV infection was more prevalent in invasive ductal carcinoma or invasive lobular carcinoma. An immunohistochemical marker for EBV (Epstein-Barr virus nuclear antigen 1 (EBNA1) clone E1-2.5) was applied to a tissue micro array section. The tissue micro array contained 80 cases of invasive ductal carcinoma, and 80 cases of invasive lobular carcinoma. Each case was scored as positive or negative for nuclear expression of EBNA1 in tumor cells using standard light microscopy. EBNA1 staining was evident in the tumor cells of 63 cases (39.4% of tumor cases). By tumor type (ductal/lobular) EBV infection was noted in 34 (42.5%) cases of invasive ductal carcinoma and 29 (36.2%) cases of invasive lobular carcinoma, this difference was not found to be significant (P=0.518). This study indicates that EBV infection is equally distributed across the ductal and lobular tumor types.

Association of human papillomavirus type 58 with breast cancer in Shaanxi province of China.

A number of reports have identified HPV DNA in breast cancer specimens and HPV type 16, 18, 31, 33, 45, and 51 were more prevalent. HPV 58 was frequently detected in cervical cancer in Shaanxi China. The aim of the present study was to investigate whether HPV 58 present in breast cancer. 169 cases of breast cancer samples and 83 benign breast lesions were analyzed. Type specific primers and oligonucliotide probe were used for the detection of HPV 58 by conventional PCR and in situ hybridization techniques. The HPV 58 viral load were measured by qPCR. p16 protein expression were evaluated by immunohistochemistry. HPV 58 E7 DNA was detected in 25 out of 169 formalin fixed paraffin embedded breast cancer tissues (14.79%) by PCR, only 1 out of 83 non-malignant breast lesions showed positive (1.20%). The results of ISH showed that 17 out of 169 (10.06%) malignant samples were positive for HPV 58 E7, and only 1 out of 83 non-malignant lesions was positive. Positive p16 immunostaining was observed in all the HPV 58 E7 ISH positive cases, but 16 out of 98 cases with HPV negative were p16 positive. The presence of HPV 58 in both normal duct epithelial cells and carcinoma in situ along with its presence in the cancer cells of the same specimen indicated the possible causal role of HPV 58 in breast cancer. The findings provide a solid morphological evidence of the involvement of HPV 58 in breast cancer development.

Epstein-Barr virus and breast cancer: epidemiological and molecular study on Egyptian and Iraqi women.

BACKGROUND AND PURPOSE: The role of Epstein-Barr virus (EBV) in breast carcinogenesis is still controversial. Unraveling this relationship is potentially important for better understanding of breast cancer etiology, early detection and possibly prevention of breast cancer. The aim of the current study is to unravel the association between EBV and primary invasive breast cancer (PIBC) in two different Arab populations (Egyptian and Iraqi women). PATIENTS AND METHODS: The study was done on paraffin-embedded tissues of 40 Egyptian and 50 Iraqi patients with PIBC in addition to 20 normal breast tissues as controls for each group. Both controls and neoplastic tissues were assessed for the expression of EBV genes and proteins (EBNA-1, LMP-1, and EBER) as well as CD21 marker by immunohistochemistry (IHC), in situ hybridization (ISH) and PCR techniques. RESULTS: Our gold standard for EBV reactivity in breast cancer cases was positivity of both EBNA1 by PCR and EBER by in situ hybridization. EBV was detected in 18/40 (45%) and 14/50 (28%) of Egyptian and Iraqi women; respectively where p=0.073, compared to 0/20 (0%) of their control groups (p<0.05). Regarding the association between EBV positivity and tumor grade, there was not any statistical significant difference between EBV presence and tumor grade in both populations where p=0.860 and p=0.976 and the calculated rank biserial correlation coefficient was 0.114 and 0.269 for Egyptian and Iraqi women respectively. CONCLUSION: Our findings show that EBV might act as a promoter for the development of PIBC and it might contribute to increased tumor aggressiveness in Egyptian and Iraqi patients.

Treatment of breast cancer stem cells with oncolytic herpes simplex virus.

Cancer stem cells have recently been isolated from several different solid tumors. In breast cancer, the CD44(+)CD24(-/low) population is considered to comprise stem-like cells. The identification of cancer stem cells has provided new targets for the development of therapeutics. Oncolytic herpes simplex viruses (oHSVs) are an effective strategy for killing breast cancer cells and treating breast tumors in preclinical models. Here, we examined the efficacy of the oHSV G47Δ in killing breast cancer stem cells. Human breast cancer cell line SK-BR-3 and human primary breast cancer cells were cultured in suspension under conditions conducive to the growth of stem cells. They generated mammospheres, which had cancer stem cell properties. The proportion of CD44(+)CD24(-/low) cells in these mammospheres exceeded 95%, as determined by flow cytometry. The mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. G47Δ contains the LacZ gene, and X-gal staining of infected cells in vitro and in vivo showed the replication and spread of the virus. G47Δ was found to be highly cytotoxic to the CD44(+)CD24(-/low) population in vitro, even when injected at low multiplicities of infection, and G47Δ treatment in vivo significantly inhibited tumor growth compared with mock treatment. This study demonstrates that oHSV is effective against breast cancer stem cells and could be a beneficial strategy for treating breast cancer patients.

Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer.

Several studies have suggested a possible role for HPV in the pathogenesis of the breast cancer. We investigated the presence of the HPV DNA in breast cancers and non malignant disease breast tissues by the use of a standard HPV detection method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA expression in HPV DNA positive breast cancer tissues. The rate of HPV infection was significantly higher in the cancer group than in controls (9/31 vs. 0/12, p = 0.04). One out of eight metastatic axillary nodes was positive for HPV infection; 2/3 of the positive HPV breast cancer patients were co-infected at the cervical site. The role of the virus in breast oncogenesis is still unclear, since our analysis failed in demonstrating the expression of viral E6 and E7 in positive HPV positive breast tumor tissues.

Immunotherapeutic potential of anti-human endogenous retrovirus-K envelope protein antibodies in targeting breast tumors.

BACKGROUND: The envelope (env) protein of the human endogenous retrovirus type K (HERV-K) family is commonly expressed on the surface of breast cancer cells. We assessed whether HERV-K env is a potential target for antibody-based immunotherapy of breast cancer. METHODS: We examined the expression of HERV-K env protein in various malignant (MDA-MB-231, MCF-7, SKBR3, MDA-MB-453, T47D, and ZR-75-1) and nonmalignant (MCF-10A and MCF-10AT) human breast cell lines by immunoblot, enzyme-linked immunosorbent assay, immunofluorescence staining, and flow cytometry. Anti-HERV-K env monoclonal antibodies (mAbs; 6H5, 4D1, 4E11, 6E11, and 4E6) were used to target expression of HERV-K, and antitumor effects were assessed by quantifying growth and apoptosis of breast cancer cells in vitro, and tumor growth in vivo in mice (n = 5 per group) bearing xenograft tumors. The mechanisms responsible for 6H5 mAb-mediated effects were investigated by microarray assays, flow cytometry, immunoblot, and immunofluorescence staining. The expression of HERV-K env protein was assessed in primary breast tumors (n = 223) by immunohistochemistry. All statistical tests were two-sided. RESULTS: The expression of HERV-K env protein in malignant breast cancer cell lines was substantially higher than nonmalignant breast cells. Anti-HERV-K-specific mAbs inhibited growth and induced apoptosis of breast cancer cells in vitro. Mice treated with 6H5 mAb showed statistically significantly reduced growth of xenograft tumors compared with mice treated with control immunoglobulin (control [mIgG] vs 6H5 mAb, for tumors originating from MDA-MB-231 cells, mean size = 1448.33 vs 475.44 mm(3); difference = 972.89 mm(3), 95% CI = 470.17 to 1475.61 mm(3); P < .001). Several proteins involved in the apoptotic signaling pathways were overexpressed in vitro in 6H5 mAb-treated malignant breast cells compared with mIgG-treated control. HERV-K expression was detected in 148 (66%) of 223 primary breast tumors, and a higher rate of lymph node metastasis was associated with HERV-K-positive compared with HERV-K-negative tumors (43% vs 23%, P = .003). CONCLUSION: Monoclonal antibodies against HERV-K env protein show potential as novel immunotherapeutic agents for breast cancer therapy.

Absence of human papillomavirus sequences in epithelial breast cancer in a Mexican female population.

The role of human papillomavirus (HPV) in breast cancer is controversial. We evaluated 118 breast carcinomas and two paraffin-embedded tissues of lesions of the nipple of Mexican patients for HPV sequences. No carcinoma sample exhibited koilocytosis, in contrast to lesions of the nipple. We subjected purified DNAs to PCR employing two HPV16/E6 or GP5/6 primer set oligonucleotides. Results showed that HPV DNA sequences were absent in the breast tissues. Absence of HPV in breast carcinoma failed to support an association between HPV infection and this carcinoma.

Limited evidence of human papillomavirus in [corrected] breast tissue using molecular in situ methods.

BACKGROUND: Human papillomavirus (HPV) has been proposed as an etiologic agent of breast cancer based on numerous reports of high-risk (oncogenic) HPV types in malignant breast tissues. However, most of those studies used standard and nested solution polymerase chain reaction (PCR) techniques, both of which are disadvantaged by vulnerability to laboratory contamination from positive control DNA and the inability to localize the signal to a specific cell type. To overcome these drawbacks, the authors of this report explored the use of in situ molecular methods of viral detection to reassess the frequency of HPV in malignant breast tissue. METHODS: In situ hybridization (ISH) was used with probes that were specific for the capsid region of 12 oncogenic HPV types, and in situ PCR (IS-PCR) was used with primers that were specific for the capsid region of HPV-16, which is the most common oncogenic HPV type. These methods were resistant to molecular contamination and allowed identification of the positive cell type. The specimens examined were malignant tissues from patients with 70 breast cancer patients at The University of Texas M. D. Anderson Cancer Center in Houston, Texas. RESULTS: HPV was observed in 4 of 70 specimens (5.7%) using ISH and in 2 of 70 specimens (2.9%) of specimens using IS-PCR. Concordance between the 2 methods was high for negative specimens; both methods yielded negative results in 66 of 70 specimens (94.3%). However, there was no concordance for the few positive specimens, probably because of differences in sensitivity and the targeted HPV types. CONCLUSIONS: Oncogenic (high-risk) HPV types were present in malignant breast epithelium very infrequently and, thus, may be causative agents of only a relatively small proportion of all breast cancers.