Fetal Cell 'Transplant' in Pregnancy May Offer Breast Cancer Protection

SEATTLE -- Fetal cells that enter the mother's circulation during pregnancy may contribute to a reduced risk of future breast cancer, according to a preliminary study.

SEATTLE, Oct. 4 -- Fetal cells that enter the mother's circulation during pregnancy may contribute to reduced risk of future breast cancer, according to a preliminary study.

Because a reduced risk of breast cancer is well recognized among parous women compared with those who are nulliparous, the researchers hypothesized that the allogeneic transplant from the fetus might provide a protective effect.

Approximately two-thirds of 82 women in the study had borne a child, but those with breast cancer had lower levels of fetal cells in their bloodstream compared with women without breast cancer, Vijayakrishna K. Gadi, M.D., Ph.D., and J. Lee Nelson, M.D., of the University of Washington here, reported in the Oct. 1 issue of Cancer Research.

Allogeneic persistent fetal cells have not been considered previously as breast cancer protection, and the current studies serve as an initial test of whether the concept merits exploration, Drs. Gadi and Nelson wrote.

The phenomenon, known as fetal microchimerism, describes the long-term persistence of small numbers of fetal-derived allogeneic cells that have established themselves in the mother. "To our knowledge, the current results provide the first indication that allogeneic fetal microchimerism could impart a protective effect against breast cancer," they concluded.

Although the transplanted cells have been implicated in autoimmune disease, fetal michrochimerism might provide hosts with immune surveillance for malignant cells, the researchers said.

They investigated 35 women with breast cancer (stages 0 to IV) and 47 without cancer, for male DNA in peripheral blood, presumed to have come from a prior pregnancy with a male fetus.

It was easier to detect the Y chromosome amid the mother's native cells in a blood sample, they said.

The prevalence and levels of male DNA were determined by real-time quantitative PCR for the Y chromosome-specific gene DYS14 in DNA extracted from peripheral blood mononuclear cells.

Among 35 women with breast cancer, only five had male DNA in their bloodstream.

Persistent fetal cells were found significantly more often in healthy women than women with breast cancer (43% versus 14%, respectively). When absence of fetal cells was treated as a risk factor for breast cancer, the odds ratio was 4.4 (95% CI, 1.34-16.99; P=0.006), the researchers said.

Restricting analysis to women known to have given birth to a son, fetal-cell presence was 14% (three of 23) in the breast cancer patients compared with 48% (14 of 29) in the controls, and the odds ratio was 5.9 (CI, 1.26-6.69; P=0.01).

The women's age at the time of the test, age at first or subsequent births, and total cell equivalents did not differ significantly between cases and controls, the researchers reported.

Because parity is known to decrease the risk of breast cancer, these observations question whether parous women who develop breast cancer are deficient in effective allogeneic immunity provided by fetal michrochimerism, the researchers said.

In certain autoimmune diseases, pregnancy is a risk factor, and alloimmunity derived from pregnancy might be contributory. Fetal cells could be primed in parous healthy women to recognize maternal cancer antigens and provide immune surveillance.

On the other hand, they suggested, among women with breast cancer, fetal immune tolerance to maternal antigens could lead to failure of allogeneic immune surveillance.

Direct evidence is not available for breast cancer, they said, although there is evidence of a similar phenomenon in the stem-cell transplantation field.

The study had several limitations, they said. Although the approach provided quantitative results, there are other possible sources of male DNA aside from pregnancies that result in the birth of a son.

These include miscarriages, induced abortion, an unrecognized miscarriage, blood transfusion, or even a vanished male twin. Nevertheless, a better attribution of the origin of male DNA would be achieved by Q-PCR for genetic polymorphisms known to be specific to a woman's children.

Some control women may be expected to develop breast cancer at a later point, so that additional studies are needed, as well as studies that include breast-feeding history.

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