Pregnancy and Breast Cancer: an Immunological Connection?

Institution: University of California, San Francisco
Investigator(s): Michael Campbell, Ph.D. -
Award Cycle: 2000 (Cycle VI) Grant #: 6JB-0031 Award: $74,600
Award Type: IDEAS II
Research Priorities
Biology of the Breast Cell>Biology of the Normal Breast: the starting point



Initial Award Abstract (2000)
Studies have found that early first pregnancy and multiple pregnancies decrease breast cancer risk; however, the mechanism(s) of these effects are not clear. There is strong evidence that hormones are involved in the etiology of breast cancer and it has been suggested that hormones are also involved in the pregnancy/breast cancer connection. In addition, a few studies have suggested that immunological factors may play a role in the protective effects of pregnancy on breast cancer. We are interested in exploring this avenue of research.

Our overall objective is to answer the question: Does pregnancy immunize against breast cancer? Our hypothesis is that immune responses generated against normal breast tissue antigens during pregnancy and/or lactation protect against subsequent development of breast cancer by targeting the same antigens present on breast cancer cells. Our long range goals are to determine how pregnancy might immunize against breast cancer, the antigens involved, and how this information could be used for developing novel diagnostic and therapeutic strategies. The goal of this study is to determine whether antibodies are generated against antigens present during pregnancy and/or lactation, to ascertain whether these antibodies also react with antigens on breast cancer cells, and to identify the antigens recognized. This study should result in a panel of antibodies and antigens in the sera of women who have had multiple pregnancies that are directed against breast cancer cells. These antibodies and antigens will aid in dissecting the role of immunological factors in the link between pregnancy and breast cancer risk and will also provide novel targets for immunodiagnostics and immunotherapies. If pregnancy is immunizing against breast cancer, then the antigens identified in this study may be ideal candidates for preventative vaccines.


Final Report (2002)
Studies have found that early first pregnancy and multiple pregnancies decreases breast cancer risk. However, the mechanism(s) of these effects of pregnancy on breast cancer risk are not clear. There is strong evidence that hormones are involved in causing breast cancer and it has been suggested that hormones are involved in the pregnancy/breast cancer connection as well. In addition, a few studies have suggested that immunological factors may play a role in the protective effects of pregnancy on breast cancer. We are interested in these latter immunological factors.

Our overall objective was to answer the question: Does pregnancy immunize against breast cancer? Our hypothesis is that immune responses generated against normal breast tissue antigens during pregnancy/lactation protect against subsequent development of breast cancer by targeting the same antigens in breast cancer cells. Our long range goals are to determine how pregnancy might immunize against breast cancer, what are the antigens involved, and how this information could be used for developing novel diagnostic and therapeutic strategies. The specific research described in this project was intended to show that antibodies are generated against antigens expressed during pregnancy and/or lactation, that these antibodies also react with antigens on breast cancer cells, and to identify the antigens recognized.

Our first specific aim was to demonstrate that sera from multiparous women react with antigens expressed on breast cancer cells. We screened the sera from 20 volunteers, 12 multiparous women and 8 nulliparous women, for reactivity against a panel of breast cancer cell lines. None of the sera demonstrated reactivity above background. This result suggested that either our hypothesis was wrong, and there is no immune response generated during pregnancy that targets breast cancer cells, or that our assay for reactivity was not sensitive enough. Assuming the later, we went ahead with specific aim 2, to identify breast cancer antigens recognized by sera from multiparous women using SEREX/PhD methodology, since this methodology is potentially more sensitive. Using a breast cancer phage display library that we constructed, we were unable to identify any antigens specifically recognized by multiparous sera compared to nulliparous sera. However, recently, we obtained a commercially available breast cancer T7 phage display library and our preliminary results with this library suggest that we may be obtaining some phage that show specific reactivity with the multiparous sera and not the nulliparous sera.

We will continue our screening with the new T7 phage display library, which in preliminary experiments looks like it will yield some breast cancer antigens that are specifically recognized by the sera from multiparous women and not by the sera from nulliparous women. One possible reason for the lack of reactivity seen in our initial screening efforts may be that most of the multiparous sera we obtained were from women whose last pregnancy was 4 or more years earlier. It may be that sera from multiparous women obtained closer to their last pregnancy will contain higher levels of the breast cancer reactive antibodies, and these antibody levels may diminish over time. Hence, in future studies, we will obtain sera from multiparous women within 1 year following their last pregnancy and use these to screen the phage display libraries.

Finally, the results of this study will be a panel of antigens defining the immune response found in the sera of multiparous women that is directed against breast cancer cells. These antigens will aid in dissecting the role of immunological factors in the link between pregnancy and breast cancer risk and will also provide novel targets for immunodiagnostics and immunotherapies. If pregnancy is immunizing against breast cancer, then the antigens identified in this study may be ideal candidates for preventative vaccines.