Epstein-Barr Virus and Breast Cancer: Lack of Evidence for an Association in Iranian Women

Abstract

Controversies regarding the role of Epstein-Barr virus (EBV) in breast cancer and lack of published literature in this regard in Iran, prompted us to assess EBV presence in 100 breast carcinoma and 42 control biopsies obtained from Iranian women. Breast carcinoma cases were comprised of 81 invasive ductal carcinoma NOS, 9 invasive lobular carcinoma, 1 apocrine carcinoma, 2 cribriform carcinoma, 2 papillary carcinoma and 5 mucinous carcinoma. Control biopsies consisted of 13 fibroadenoma, 9 benign epithelial proliferation (adenosis and sclerosing adenosis), 9 usual ductal hyperplasia, 4 atypical ductal hyperplasia, 4 non-proliferative fibrocystic changes and 3 normal breast tissue. To identify EBV-infected cells we applied immunohistochemical analysis, using monoclonal antibody against Epstein-Barr virus-encoded nuclear antigen 2 (EBNA-2) and latent membrane protein 1 (LMP-1). Further, polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers that cover the EBV encoded RNA (EBER) and BamHIW regions. EBNA-2 and LMP-1 immunohistochemistry were negative in all breast cancer and control specimens. Using PCR, none of the 100 breast cancer samples or the 42 control specimens showed detectable EBV DNA. These results indicate that EBV may not play a significant role in the etiology of breast cancer in Iranian women.

Epstein-Barr Virus and Breast Carcinoma in Iran

“…Although the presence of a virus alone does not establish a causal role in the disease and other techniques are not used to prove the attendance of EBV-DNA in tumor cells, our findings with 9.3% positivity, in addition to the previously reported positive results, supports the possibility of an etiologic relationship. The proof of etiologic role of EBV in the induction of breast carcinoma needs more efforts using more specific and sensitive techniques (1,2,16,17). If the association of one or more of these viruses with breast cancer can be established, there is a possibility of prevention by anti-viral treatments and vaccination strategies (11).…”

“…The 3 previous studies performed in Iran (Table 3) showed no significant positive results; Eghbali and colleagues (5) had a higher but statistically insignificant rate of HBV-DNA in malignant cases using the PCR technique. Kadivar et al (16) reported that EBNA-1 and LMP-1 were negative in all 100 breast carcinoma cases and control subjects, which were approved by the PCR method. Also, the study by Fadavi et al (17), using PCR and RT-PCR, showed negative EBV-DNA in 18 breast cancers.…”

“…The false positive results may be due to contamination, infected circulating lymphocytes, cross-reaction of antibodies or use of ISH, which determines the virus with qualitative but not quantitative method. The negative results may be due to geographical differences and various distribution patterns of virus, low amount of the virus, and low sensitivity of used techniques (16). Also, some techniques may not distinguish between viruses in tumoral cells and those in tissue lymphocytes (16,17).…”

Presence of Human Papillomavirus and Epstein-Barr Virus in Breast Cancer Biopsies as Potential Risk Factors

“…On the other hand, the expression of EBV latent protein expression has also been assessed in breast cancer cell lines in vitro and in vivo 22 , as well as the oncogenic capacity of its viral proteins 6 . However, some studies have failed to find any relationship between EBV and breast cancer [23][24][25] . These evidences allow for a possible relationship between breast cancer and infection, either with EBV or HPV, to be proposed, based on which these viruses can be regarded as risk factors in the development of this disease that causes many deaths in the female population worldwide.…”

Presencia del virus del papiloma humano y del virus de Epstein-Barr en biopsias de cáncer de mama como posibles factores de riesgo

“…Por otra parte, también se ha evaluado la expresión de proteínas latentes del VEB en líneas celulares de cáncer de mama in vitro e in vivo 22 , así como también la capacidad oncogénica de sus proteínas virales 6 . Sin embargo, algunos estudios no han encontrado ninguna relación entre el VEB y el cáncer de mama [23][24][25] . Estas evidencias permiten plantear una posible relación entre el cáncer de mama y la infección, bien sea por VEB o por VPH, a partir de lo cual pueden considerarse estos virus como factores de riesgo para el desarrollo de este cáncer que causa muchas muertes en la población femenina en todo el mundo.…”