Breast cancer is both an ancient disease, first described by the Egyptians , and a disease of civilization, since its incidence has increased in the last century.
In mice, MMTV is transmitted horizontally as an infectious particle containing viral RNA or vertically in the murine germline as an endogenous proviral DNA genome. MMTV replicates in the mothers' mammary glands where the infectious B-type particles accumulate in milk. When the nurslings ingest the virus, it invades the gut-associated lymphoid tissues and infects B- lymphocytes. To aid viral replication, MMTV uses a superantigen, encoded by the orf gene in the viral long terminal repeat (LTR) region, to activate specific T-lymphocyte subsets. This serves to stimulate viral replication as well as clonal amplification of T lymphocytes, which provides a vehicle for viral passage from the gut-associated lymphatic tissue to the breast. Although viral replication is maximal in the breast epithelium, hormone stimulation is still required to activate the corticosteroid response elements in the retroviral LTR. During pregnancy, viral replication is increased, which leads to hyperplasic nodule formation that can eventually lead to tumor formation.  MMTV can also be transmitted to the offspring as proviral DNA in a Mendelian fashion. MMTV does not contain an oncogene, but it has been shown that proviral-DNA can integrate close to cellular proto-oncogenes and enhance their activity. 
What is MMTV’s role in human breast cancer on the globe? Our results are similar with the results of a series of studies that could not detect the presence of the MMTV in human breast cancer samples. Tabriz et al.  evaluated the same MMTV-like target sequence as us by RT-PCR using the same primers, and did not detect any virus particle in breast cancer tissues of 40 Iranian women. Perzova et al.  analyzed the prevalence of MMTV env sequences in 66 samples of FFPE (formalin-fixed paraffin-embedded) or snap-frozen biopsies of breast tissue (US patients) by PCR and took supplementary measures to prevent carry-over contamination with murine DNA; they concluded that the MMTV copy numbers detected in the breast cancer specimens were too low to be derived from a monoclonally integrated expanded tumor cell sample. Fukuoka et al.  investigated in Japan 46 breast cancer patients and 3 patients with benign mammary tumors and used PCR and Southern blot hybridization; their team could not detect the MMTV env gene-like sequence in any of the samples tested.
However, there are several reports on the MMTV env gene in human breast cancer samples. , , ,  Additionally Johal et al. found MMTV like virus sequences by PCR in 5% (4/91) of breast milk samples from healthy lactating women from Australia, . Furthermore, MMTV-like sequences were found in the saliva  and peripheral blood lymphoid cells , suggesting that viral transmission in humans is similar to that seen in mice, occurring via breastfeeding and infection of mucosa-associated lymphocytes before reaching the breast tissue.
The contrast between the different outcomes of the studies may indicate that there is a regional virus epidemiology. Our study is the first one in Romania and even South-Eastern Europe which analyzes the prevalence of MMTV virus infection in human breast tissue. Based on our sample the results indicate that breast cancer is not likely to be related to the MMTV infection in Romania. The negative result is most likely explained by the transmission vectors of the virus and the geographic distribution of Mus musculus sp. domesticus – the native MMTV reservoir. It has been proposed that a higher prevalence in some areas of Mus musculus domesticus in the vicinity of humans, which is the species of mouse that carries the infectious MMTV, is correlated to a higher prevalence of human breast cancer.  M. m. domesticus seems to be less present in South-Eastern Europe, where M. m. musculus is the predominant species . In relationship to MMTV this variability of species needs to be further explored, but we found no reports of naturally occurring MMTV infection in M. m. musculus. Callahan et al  studying several feral mouse species stated that M. m. musculus specimens from Czechoslovakia did not carry MMTV, although all mice species studied had small fragments of inserted MMTV which is explained by the “accumulation of evolutionarily divergent MMTV-alpha insertions into the mouse germ line”. Ford et al  could not identify MMTV in first-generation Australian-Vietnamese women, in comparison to Caucasian-Australian woman (42.2%). It is known that in South-Eastern Asia the dominant mouse species is not M. m. domesticus, but M. m. castaneus.
Recently, Wang et al  described a regional distribution of MMTV-positive breast tissue specimens in China: in Southern China the positivity was 5.71%, compared to 22.62% in Northern China (p < 0.05). This different prevalence is likely to be linked to the distribution of M. m. domesticus and M. m. castaneus.
Furthermore, even Mus musculus sp. domesticus, also known as “western house mouse”, since its spread to Europe from Asia in the postglacial period , clustered in somewhat different local populations , and local subpopulations may have different rates of infection with MMTV, which might explain the variable positivity of MMTV in Western countries, ranging 20–40%. Another reason for the variability of the rate of association of MMTV to human breast cancer is the presence of a possible intermediary host, the dog. Laumbacher et al  studied dog-human contact epidemiologically in Bavaria, Germany and found that more than twice the number of breast cancer patients kept dogs permanently in the last 10 years leading up to the diagnosis compared to control individuals (37.7% vs. 14.8%, p = 0.0000003, relative risk 3.5).
Because breast cancer is more prevalent among women of higher socio-economic status, it has been hypothesized that this may be due to a late exposure to MMTV infection from mice, as compared to infection during early life among girls of low socio-economic status and hence early immunity. 
As human breast cancer progresses, the MMTV viral load increases but it falls in late-stage invasive breast cancer.  The lack of identification of MMTV in advanced breast cancer may be due to the breakdown of cell physiology, but our patient sample consisted of early stage, non-metastatic breast cancer patients.
Another explanation for the divergent results regarding the MMTV infection in humans might be that some positive results were due to carry-over contamination of human samples with previously amplified murine MMTV DNA. Rodent DNA might be present in the building’s walls and ventilation systems, most likely as small particulate matter.  We consider this scenario very unlikely in all of the MMTV-positive studies, although might have had happened in some, taking into account the extreme measures taken to avoid contamination by most of the laboratories.
While it is clear that the association between MMTV infection and human breast cancer is still a debatable topic, most results indicate that a correlation cannot be ruled out. Proving that MMTV is an etiologic agent for human breast cancer will probably require non-PCR based traditional retrovirology techniques such as virus isolation and determination of monoclonal integration in tumor cells. This would certainly be a breakthrough in oncology and would open the gates to the prevention of breast cancer through (1) hygiene measures, (2) counseling of those less than 5% of MMTV-infected women to find alternatives to breastfeeding and (3) the development of a vaccine. If in Western countries and Australia the involvement of MMTV in breast cancer probably occurs in 20–40% of patients, such measures would lead to a proportional reduction of newly diagnosed breast cancer cases in about one or two generations. MMTV-related breast cancers tend to be less aggressive as well. 
Other virus infections have been proposed as well as causative agents of breast cancer; the most studied is bovine leukemia virus (BLV). 
Breast cancer remains one of the most mysterious human cancers, since most cases cannot be linked to specific risk factors.