Breast Cancer Metastasis: a Heritable Trait?

Institution: Stanford University
Investigator(s): Alice Whittemore, Ph.D., M.A. -
Award Cycle: 2006 (Cycle 12) Grant #: 12IB-0167 Award: $264,595
Award Type: IDEA
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle

Initial Award Abstract (2006)
Why do some breast cancers spread to other organs while others donít? There are many , some relating to the biology of the cancer and others relating to treatment options. Maybe, for some people, cancer spread reflects altered genes that are passed from generation to generation in their family. Recently, scientists discovered a gene in mice that, when altered, causes their mammary cancers to metastasize. Now it is important to determine if a similar genetic predisposition occurs in humans, because if it does, we can develop treatments specially targeted to patients whose cancers may be more likely to spread.

For the past 10 years, the Breast Cancer Family Registry (Breast CFR) has been collecting information about families with multiple cases of breast cancer. Therefore, this resource already has data about breast cancer characteristics in many different families with at least two (and often more) cases of invasive breast cancer. We will use this information to look for correlations within families in the tendency of patientsí breast cancers to spread. Because people within a family share genetic information, our hypothesis is that the metastatic tendency is more similar within families than between families. If this is true, there may be some specific genes that cause this association, and we will plan further studies to discover them. And if we find them, patients could be tested for these genetic markers and have their treatments tailored accordingly.

Information will be collected about breast cancer in families in which there are two or more women with breast cancer. The information will include the stage of the cancer at the time it was diagnosed and the laboratory markers that show how aggressive the tumor was at the time of diagnosis. In addition, information will be collected regarding whether the cancer has recurred and if so, how long it took. We will conduct statistical comparisons on several of these factors to see how they are different within families and between families.

Breast cancer research often focuses on why the disease occurs and less often on why it spreads. But cancer spread is life threatening and therefore important. If we find correlation within families in cancer spread, we will look for genes that cause it. Finding such genes may help devise new treatments to prevent the spread.

The Breast CFR has two advocates that sit on its Steering Committee and participate in the approval process of scientific projects that use Registry data. Because we are using only data about breast cancers that have occurred in the past, we do not anticipate significant risks to the individuals whose information is being used in this study. The project will address the human issues associated with breast cancer because we expect to find that there are stronger associations of recurrence within families, since people within a family are likely to share genetic information. If this is true, there may be some specific genes that cause this association, and we will plan another study to discover them. And when we find them, women could be tested for these genetic markers and have their treatments tailored to their specific needs.

Final Report (2008)
Animal experiments support the hypothesis that the metastatic potential of a patientís breast cancer is a heritable trait influenced by her genetic background. If this hypothesis is verified in humans, it would have major implications for the early detection, screening, diagnosis and treatment of breast cancer. However there are few human data available to test the hypothesis.

We used retrospective cohort data from 743 female breast cancer patients in 242 families registered with the Fox Chase Cancer Center in Philadelphia and the Huntsman Cancer Institute in Salt Lake City to test the hypothesis that the prognostic features at diagnosis of blood relativesí cancers are correlated, and that after adjustment for possible correlation in prognostic features, the metastatic risks of blood relatives are correlated.

We observed 255 metastatic outcomes (34.3%) in a mean followup of 11.7 years. The data provided no evidence for familial correlation in prognostic features at diagnosis. Only 17% of the variation in prognostic scores was due to differences between families, with the remaining 83% due to variation within families. Moreover, the correlation coefficients for nodal and hormonal statuses were close to zero for all pairs of blood relatives. Similarly, the data did not support familial correlation in risk of subsequent metastasis. None of the correlation coefficients differed significantly from zero, regardless whether the outcome was occurrence of metastasis or metastasis-free survival time, and regardless of the degree of relationship of the relatives.

These findings suggest that a family history of metastatic breast cancer does not contribute substantially to a breast cancer patientís risk of metastasis, after adjustment for the prognostic features of the cancer.