A new Italian study has reported that Cancer Antigen 15-3 (CA 15-3) is an independent prognostic marker for metastasis and death in patients with operable breast cancer. CA 15-3 measures the same protein as CA 27.29 and is used similarly. The study was designed to investigate the prognostic value of presurgical CA 15-3 levels in a large group of women with early breast cancer. The study included women who were treated at the European Institute of Oncology in Milan from 1998 to 2005. The authors explored the association between breast cancer recurrence and CA 15-3 values measured before breast cancer surgery (or any other breast cancer treatment). The average presurgical CA 15-3 level in study participants was 17.0 U/ml (a level not indicative of metastatic disease).

CA 15-3 was found to be associated with age at diagnosis, tumor size, lymph node involvement, Ki-67 (proliferation), tumor grade, HER2 expression, breast cancer subtype, and perivascular invasion (when tumor cells migrate along the outside of blood vessels). CA 15-3 was also found to be independently associated with subsequent distant metastasis. Women with baseline CA 15-3 of at least 20 U/ml were 34% more likely to develop a distant metastasis than those with CA 15-3 under 20 U/ml. A level risk of metastasis was found for CA 15-3 values to about 15-20 U/ml. However, for values above 20 U/ml, the risk of metastasis and death increased with increasing values of CA 15-3. The authors conclude that CA 15-3 provides information in addition to commonly used prognostic factors and should be considered when deciding on treatment.

Comments regarding the study

Like CA 27.29, CA 15-3 is not useful for cancer screening. CA 15-3 levels are typically not elevated in patients with breast cancer localized to the breast; only 15% to 30% of such patients will have levels above 25 U/ml. CA 15-3 may be used in the surveillance of asymptomatic breast cancer survivors, however a normal CA 15-3 level does not guarantee the absence of metastatic breast cancer. Some women with stage IV breast cancer have tumors that do not shed CA 15-3. However, for those that do, CA 15-3 can start to become elevated as much as six months before any symptoms of relapse appear. Unfortunately, it is unclear whether administering systemic therapy based on such lead time improves survival. Therefore, there is disagreement on the usefulness of regularly measuring CA 15-3 (or other tumor markers) in asymptomatic survivors and some oncologists are unenthusiastic about performing such monitoring.

The primary use of CA 15-3 is to monitor stage IV patient response to breast cancer treatment. Increasing levels of CA 15-3 over time may indicate that a patient is not responding to treatment or that the cancer is recurring. Elevated CA 15-3 can be found in approximately 50% of women with lymph node metastases and 90% of those with distant metastases.