UT MD Anderson research finds predictive value of circulating tumor cells in early stage breast cancer

Largest study to show benefit beyond the metastatic setting

HOUSTON — Circulating tumor cells (CTCs), established in the metastatic breast cancer setting for predicting a woman’s chance of recurrence and survival, have now shown similar value in early stage breast cancer, according to research from The University of Texas MD Anderson Cancer Center.

Published in the Lancet Oncology, the study is one of the first and is the largest to show this new predictive value of CTCs. It may help determine which earlier stage breast cancer patients need additional treatment and intervention in the adjuvant setting.

MD Anderson research played an integral role in understanding the predictive value of CTCs in the metastatic setting -- the presence and higher number of CTCs correlated with earlier time to recurrence, and poor overall survival.  Their value also has been shown in metastatic colorectal and prostate cancers.

Researchers have long been trying to determine a similar value for CTCs for earlier stage patients, says Anthony Lucci, MD, professor in MD Anderson’s Department of Surgical Oncology. Currently, in these women, axillary lymph node dissection remains one of the best predictors of prognosis.

“There are a significant number of non-metastatic breast cancer patients for whom you remove their tumor, take out the lymph nodes, treat them with systemic therapy, and render them no evidence of disease. However, around two years later -- a peak time for recurrence -- about 25-35 percent of those women will present with metastatic disease somewhere else, and we wanted to understand why,” says Lucci, the study’s lead author and study principal investigator. “With this study, we wanted to identify cancer cells in circulation, and thereby determine if those cells were actually predictors of recurrence.”

For the prospective study, the researchers collected CTCs via blood and bone marrow draws from 302 MD Anderson Stage I, II and III breast cancer patients immediately prior to their surgery. (This study only reports the CTCs collected by blood draw.) None had undergone chemotherapy prior to their blood being drawn. Patients with bilateral breast cancer and/or other malignancies within five years of the breast cancer diagnosis were ineligible.

The CTCs were measured using the Veridex Cell Search System. Researchers correlated the findings of CTCs with tumor characteristics such as: size and grade; estrogen, progesterone, and HER2 status; and lymph node involvement. The mean age of women enrolled in the study was 54; the median follow up time was 35 months. The researchers found one or more CTCs in 73 patients, or 24 percent; 29, or 10 percent, had two or more CTCs; and 16, or 5 percent, had three or more.

Detection of one or more CTCs predicted both decreased progression-free survival (PFS), or early disease recurrence, and overall survival.  Eleven of the 73 patients, or 15 percent, who had at least one CTC relapsed, compared to seven, or 3 percent, of the 229 women who were found to have no CTCs.

An increased number of CTCs correlated with decreased PFS and overall survival. At two years, the PFS rate in women with one or more, two or more, or three or more CTCs was 87 percent, 79 percent and 69 percent, respectively, compared to 98 percent in those without CTCs. At two years, the overall survival rate in those with one or more, two or more, or three or more CTCs was 94, 89, 81 percent, respectively, compared to 99 percent in those without.

“We can now reliably detect circulating tumor cells in 25 percent of non-metastatic breast cancer patients with no evidence of disease, and know that their risk of recurring or dying is around four times higher than those without these cells in their blood circulation,” said Lucci.

Interestingly, says Lucci, neither tumor size nor other primary tumor characteristics accurately predicted the presence of CTCs.

“Our findings determine that cancer cells can break free of the primary tumor very early on, and even the earliest stage cancers can shed these dangerous cells. Our next area of research focus is determining which of the circulating tumor cells are able to establish metastasis elsewhere, and which do not survive outside of the primary tumor area,” said Lucci.

The research is not yet practice changing. A larger, multi-center trial validating the findings must next be conducted before CTCs can impact clinical decision making for systemic therapy in early stage patients, said Lucci. He and his team also plan are currently looking at the markers on the individual CTCs to determine if they could be targets for additional therapy.

Other authors on the all-MD Anderson study include: Carolyn S. Hall, Ph.D., Ashutosh K. Lodhi, M.D., professor, Anirban Bhattacharyya, M.D., Amber E. Anderson, and Isabelle Bedrosian, M.D., associate professor, Henry Kuerer, M.D., Ph.D., professor, all of the Department of Surgical Oncology; Lianchun, Xiao, Department of Biostatistics; and Savitri Krishnamurthy, M.D., Department of Pathology.

The research was supported by The Society of Surgical Oncology Clinician Investigator Award, The Morgan Welch Inflammatory Breast Cancer Program, The Institute for Personalized Cancer Therapy and the State of Texas Rare and Aggressive Breast Cancer Research Program.

None of the authors declare conflicts.