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Evidence in Favor of the Existence of Human Breast Cancer Virus¹

Institute for Medical Research, Camden, New Jersey 08103

The existence in some women of a virus that is related to the mouse mammary tumor virus is evidenced by the following. Type B particles are occasionally found in human milk. A complication is the fact that most human milks destroy or damage the murine, mammary tumor virus (MuMTV) and its RNA-directed DNA polymerase (RDDP) when the mouse virus is added to the human milk. Human milk presumably has the same effect on any human RNA virions present. RDDP is found in many human milks although because of the destroying factors (not present in mouse or cow's milk), its presence usually depends on the freshness and/or amount of destroying factors in human milk; RDDP is associated with particles having the same buoyant density as MuMTV (1.18 to 1.22 g/ml versus 1.15 to 1.17 g/ml for leukemia viruses). RDDP is associated with a 35 S or 70 S RNA which is a characteristic of RNA tumor viruses. Human RDDP responds to magnesium ions for activity with a synthetic template, polyribocytidylic·deoxyguanylic (12 to 18 nucleotides long), in agreement with MuMTV, whereas mouse leukemia virus RDDP responds to manganese ions. Hybridization studies indicate a relationship between MuMTV RNA and human breast cancer RNA. (Using the S₁ nuclease treatment and most stringent procedures, the RNA from 8 out of 22 human breast tumors hybridized from 18 to 77% of the MuMTV DNA probe; none hybridized with Mason-Pfizer monkey virus probes.) Using the migration inhibition factor test, positive responses of human leukocytes to homologous in situ breast cancer tissue are correlated with responsiveness to MuMTV. Many human sera completely neutralize MuMTV. (The neutralizing activity resided in the globulin fraction, was absorbed by RIII milk, but was not absorbed by MTV-free C57BL milk.) Some human breast cancer patients' sera contain material that precipitates specifically on the membrane of budding MuMTV virions as demonstrated with peroxidase-coupled anti-human globulin. Slices of mouse tumors rich in MuMTV react, in immunofluorescence tests, with sera from some women with breast cancer or fibrocystic mastopathy.

The means of virus transfer (route of infection) in humans remains unknown. RNA sequences homologous to MuMTV probes are found in human breast cancers, but to date no homologous DNA sequences have been found. The virus does not seem to be endogenous in humans.

¹ This study was conducted under USPHS Contract NO1-CP-33339 within the Virus Cancer Program of the National Cancer Institute; Grant CA 08740 from the National Cancer Institute; General Research Support Grant FR-5582 from the Division of Research Facilities and Resources; and Grant in Aid M-43 from the State of New Jersey.

Received 4/25/74. Accepted 6/10/74.

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