Virus Linked to Breast Cancer

SAN ANTONIO, Dec 15 -- Evidence is mounting that the so-called human mammary tumor virus (HMTV) can actually causes breast cancer, New York researchers said.

HMTV -- almost identical to a retrovirus that causes breast cancer in mice -- is found in about 30% of human cases, according to James Holland, M.D., of Mount Sinai School of Medicine.

In breast cancer tissue samples from North America, about three in 10 contain the HMTV provirus, compared with less than 2% in samples from reduction mammoplasty and none in samples from other cancers, Dr. Holland told a plenary session at the San Antonio Breast Cancer Symposium.

Moreover, he reported, he and colleagues have recently shown that HMTV is capable of infecting a range of human cells, including mammary epithelial cells, peripheral blood mononuclear cells, T-cells, and B-cells.

The combination of those findings excludes the possibility that the provirus is a part of the human genome, passed down from mother to daughter, he said. "It is not inherited, but horizontally acquired," he said.

Dr. Holland and colleagues have been looking into the link between HMTV and cancer for several years, after earlier research showed that the mouse version is a definite cause of breast cancer in the animals.

"We though that if human breast cancers were due to a virus, it would be a kissing cousin to the mammary tumor virus in mice," Dr. Holland said.

A close look at the mouse virus showed that a 690 base-pair segment of the env gene is unique in known genetic sequences from all living creatures. Using that sequence as a probe, the researchers were able to find examples of the human virus, which differs from the mouse version only in a single gene, he said.

Other data suggest that HMTV -- which is genetically 95% identical to its counterpart in mice -- may be a zoonosis, a human disease acquired from animals like HIV or influenza.

The argument is based on the observation that high rates of human breast cancer tend to coincide with places where the common house mouse, mus domesticus, lives. The species has very high rates of murine mammary tumor virus, as well as "a lot of breast cancer," Dr. Holland said.

So, for instance, in Western Europe and the Americas human breast cancer rates are high, but in Eastern Europe -- where other species of mice live -- the rates are lower.

Dr. Holland extended the argument here with new data from Africa and Asia, showing again that living with mus domesticus implies high rates of breast cancer, while living with other species is associated with lower rates.

"Human mammary tumor virus," he concluded, "is linked to a large proportion of human breast cancers."

While the theory has been studied for some time, Dr. Holland and colleagues are "pulling the pieces together," commented John Mackey, M.D., of the Cross Cancer Center in Edmonton, Alberta.

Dr. Holland "has made a stronger argument that HMTV, which is slightly different from the murine version, is at play" in many cancers, Dr. Mackey said, noting that the presentation added two key pieces of information to what was already known:

• The report extended the link between mouse habitat and the human virus to Africa and Asia.
• It showed that HMTV can be transmitted between human cells in culture.

But "it's not proven, by any means," Dr Mackey concluded.

Another researcher, Kevin Hughes, M.D., of Massachusetts General Hospital in Boston, said the report wasn't strong enough to convince him that the virus splaying a role in human breast cancer. But "I think it's compelling enough to require further study," he said.

He added that -- if the theory is eventually accepted -- it will be important not to "stigmatize women with breast cancer as possible carriers of an infectious disease."