So Close and Yet so Far...

The holy grail in women's oncology is early detection. This is most painfully true for ovarian cancer, where symptoms often suggest that the disease has already advanced. Unlike the mammogram or pap smear, there is no way to screen the general population for ovarian cancer. For women with ovarian cancer, the protein CA-125 can be followed in a majority of women with advanced disease. That is, for women whose CA-125 was elevated at diagnosis, it can be a good way to tell how she is responding to treatment and her overall status once treatment is completed. A rise in the CA-125 can herald that cancer has returned about 8 months before signs or symptoms would otherwise arise. Given that a blood test can be used to follow the woman with ovarian cancer, it has been a challenge to find a test that may help us find women with ovarian cancer while still early. There are a number of other proteins that have been touted as a marker for ovarian cancer, including proteins called HE4, CA72-4, MMP-7, and CA15-3. The question has been: do these add to the usefulness of CA-125? Could they be better than CA-125?

At the 2009 American Association for Cancer Research Meeting (AACR), an abstract was presented by Daniel Cramer from Harvard Medical School/Brigham & Women's Hospital, on behalf of researchers nationwide involved in a large screening trial for prostate, lung, colon, and ovarian cancers, called the PLCO screening study.

In the first part of the study, investigators screened more than 50 markers from the blood of three groups of women: those with ovarian cancer with serum taken at the time of diagnosis (n=160) versus women without any cancer (n=160) versus blood taken from the general population (n=480). The proteins that fell out with the greatest accuracy were CA-125, HE4, CA72-4, Transthyretin, HK6, B7H4, MMP7,and CA15-3. In the second part of this study, the blood samples from women who were part of the PLCO study, who had blood drawn months to years prior to a diagnosis of ovarian cancer, were used to test these proteins with proposed screening panels of markers (ie, a group of markers that were suggested to be more accurate than single protein levels). The end result was fairly sobering: the panels did not do much better than the CA-125 alone. However, they made two important observations: other markers (HE4, CA72-4, and MMP-7) seemed to increase the performance of CA-125 and the measurement of values over time seemed to help too. These observations may some day help to formulate a screening strategy, but for now, measurement of these values off a study cannot be recommended (particularly in light of the PLCO trial which reported that screening did pick up ovarian cancer, although in a significant proportion the disease was advanced at diagnosis. Whether or not screening improves survival has yet to be answered.

For more on this, check out the AACR media page at: www.aacr.org/home/public--media/aacr-press-releases.aspx?d=1317.