A human MMTV-like betaretrovirus linked to breast cancer has been present in humans at least since the copper age.

The betaretrovirus Mouse Mammary Tumor Virus (MMTV) is the well characterized etiological agent of mammary tumors in mice. In contrast, the etiology of sporadic human breast cancer (BC) is unknown, but accumulating data indicate a possible viral origin also for these malignancies. The presence of MMTVenv-like sequences (MMTVels) in the human salivary glands and saliva supports the latter as possible route of inter-human dissemination. In the absence of the demonstration of a mouse-man transmission of MMTV, we considered the possibility that a cross-species transmission could have occurred in ancient times. Therefore, we investigated MMTVels in the ancient dental calculus, which originates from saliva and is an excellent material for paleovirology. The calculus was collected from 36 ancient human skulls, excluding any possible mouse contamination. MMTV-like sequences were identified in the calculus of 6 individuals dated from the Copper Age to the 17th century. The MMTV-like sequences were compared with known human endogenous betaretroviruses and with animal exogenous betaretroviruses, confirming their exogenous origin and relation to MMTV. These data reveal that a human exogenous betaretrovirus similar to MMTV has existed at least since 4,500 years ago and indirectly support the hypothesis that it could play a role in human breast cancer.

Chemotherapy and targeted therapy for breast cancer patients with hepatitis C virus infection.

BACKGROUND: Hepatitis C virus infection (HCV) is a major health problem in Egypt. Breast cancer is the most common cancer among Egyptian women. Considering that both diseases are frequent in the Egyptian population, it is likely that many women are affected by both. PURPOSE: To evaluate patient safety and applicability of chemotherapy in chronic hepatitis C virus-infected patients with breast cancer. SUBJECTS AND METHODS: We performed retrospective survey of 58 Egyptian patients diagnosed with both diseases. We retrospectively investigated the baseline patient and tumor characteristics, the toxicities of chemotherapy, and the changes in HCV viral load before and after chemotherapy, in addition to treatment received for HCV infection. RESULTS: Forty-four (75.9%) out of the 58 patients received chemotherapy with or without trastuzumab and one patient received lapatinib. We reported 2 patients who had HCV viral reactivation. Treatment with trastuzumab or Lapatinib was not associated with elevation in liver enzymes or change in HCV RNA viral load. Treatment discontinuation occurred in 31.8% (14/44) of patients due to complications. Dose reductions and/or dose delays were common (27.2%). Elevated liver enzymes were developed in 20 out of 44 (45.5%) patients who received chemotherapy. Three patients received antiviral treatment concomitant with chemotherapy with no significant complications. CONCLUSIONS: Greater attention should be paid to the possibility of complications including HCV reactivation, fulminant hepatitis, and interrupted chemotherapy treatments in breast cancer patients with chronic HCV infection receiving immunosuppressive drugs. Close monitoring of patients with breast cancer and HCV infection should be done.

Herpes infections in breast cancer patients treated with adjuvant chemotherapy.

OBJECTIVE: There is little information on Herpes zoster infection in breast cancer patients as a complication during adjuvant chemotherapy. The aim of this study is to evaluate the incidence of Herpes zoster and simplex infections in this patients setting. METHODS: We analyzed 623 early-stage breast cancer patients in our Institute over a period of 7 years (1998-2005). Four-hundred and sixty-one patients were treated with anthracycline-based chemotherapy, 116 with CMF and 46 with taxane-containing regimens. RESULTS: Twelve (1.9%) developed herpes zoster; 9 patients, receiving anthracycline-based chemotherapy, two taxane-containing regimens, and one CMF regimen. Herpes zoster infection required treatment delay in 6 patients. Adjuvant chemotherapy was delayed for 1 week in 2 patients, while in 4 patients with more severe symptoms chemotherapy was delayed for 2 weeks. One patient, despite i.v. acyclovir, had severe postherpetic motor neuropathy with a permanent ambulation impairment, and chemotherapy was stopped. In our study, herpes zoster occurred in 55/1,000 cases/year. The reported incidence in the general population varies between 2.2 and 4.1 per 1,000 patients/year; therefore, the risk of developing herpes zoster in these patients may be 13- to 25-fold higher compared to the incidence in the general population. In addition, 13 of 623 patients developed herpes simplex. CONCLUSION: Our findings suggest that adjuvant chemotherapy can facilitate reactivation of herpes infection.

Progression from normal breast pathology to breast cancer is associated with increasing prevalence of mouse mammary tumor virus-like sequences in men and women.

Mouse mammary tumor virus (MMTV)-like sequences have been found in up to 40% of breast cancer samples but in <2% of normal breast tissue samples from Australian women studied by our group. Screening of a larger and more diverse cohort of female breast cancer samples has now shown a correlation of MMTV-like sequences with the severity (grade) of breast cancer. Thirty-two percent (43 of 136) of female breast cancer samples were positive for MMTV-like sequences when screened using PCR. A significant gradient of MMTV positivity was observed with increasing severity of cancer from 23% of infiltrating ductal carcinoma (IDC) grade I tumors to 34% of IDC grade II tumors (P = 0.00034) and 38% of IDC grade III tumors (P = 0.00002). We also report for the first time the detection of MMTV-like sequences in 62% (8 of 13) of male breast cancer samples and 19% (10 of 52) of male gynecomastia samples screened. MMTV-like sequences were demonstrated in various premalignant breast lesions of females, including fibroadenoma (20%) and fibrocystic disease (28%) samples, at a significantly higher prevalence than that seen in normal breast tissue (1.8%; P = 0.00001). Study of a longitudinal cohort of female breast cancer patients indicated that MMTV was co-incident with tumor but was not present when tumor was absent on histology. These results support the association of MMTV-like sequences with development of breast tumors in men and women and suggest association of MMTV with increasing severity of cancer.

Absence of Epstein-Barr virus EBER-1 transcripts in an epidemiologically diverse group of breast cancers.

Epstein-Barr virus (EBV), a ubiquitous herpesvirus associated with certain lymphomas and carcinomas, has been identified within the malignant cells of a small proportion of breast tumors. As breast cancer is a very common malignancy in women, a pathogenetic role of EBV for even a subgroup of patients could have important implications for etiology and prevention. Therefore, we attempted to confirm the EBV-breast cancer association by exploring it in a representative case series stratified by characteristics that modify breast cancer risk. We studied a sample of 97 female and 28 male patients identified from a US population-based cancer registry. Patients were selected randomly within age, sex, ethnicity and tumor estrogen-receptor status groups. With their archived tumor tissues, we examined EBV presence using in situ hybridization for the EBER-1 transcript. In the 107 technically adequate specimens, we did not detect this viral transcript in any tumors, including one from a woman who also had an EBER-positive nasopharyngeal carcinoma. Our uniformly negative findings are extremely unlikely to have occurred by chance and cannot be attributed to selective sampling, as our study group included persons at diverse risk for breast cancer. We conclude that the EBV EBER-1 transcript is not commonly expressed in breast cancer, based on a broadly representative case series, though we cannot exclude an association of EBV within a particular population subgroup.

Breast cancer in a man with human immunodeficiency virus infection.

Non-acquired immunodeficiency syndrome (AIDS)-defining neoplasms are being increasingly recognized in patients infected with the human immunodeficiency virus (HIV). The incidence of Hodgkin's disease and seminoma has recently been reported to be increasing in these patients. This article describes the second case of breast cancer in an HIV-infected male patient. A total of 11 cases of coincident breast cancer and HIV infection have previously been reported. It may be prudent to consider breast cancer in the differential diagnosis of an axillary mass in an HIV-infected patient.