SAN FRANCISCO—Women with triple-negative breast cancer (HER2-negative, progesterone-receptor-negative, and estrogen-receptor negative) who have a complete pathological response after neoadjuvant chemotherapy have a better prognosis than those who have residual disease after treatment. Until now, however, investigators have not examined whether all residual disease is equal.
In a new study reported here at the Breast Cancer Symposium (Abstract 106), German researchers found that women with small residual disease (i.e., classified as ypT1-2) after neoadjuvant chemotherapy had significantly better overall survival and disease-free survival rates two years after surgery than women with larger-volume residual disease (ypT3-4).
“The practical implication of this study is that those who are in the ypT3-4 group after neoadjuvant treatment absolutely need post-neoadjuvant treatment,” said the study's first author, Peter Kern, MD, Associate Senior Consultant at the University Hospital of Essen Comprehensive Cancer Center. “On the other hand, we can now reassure the women who are in the ypT1-2 group.”
The researchers analyzed data from 3,758 patients with triple-negative breast cancer who were treated at the West German Breast Center in Essen or an affiliated hospital between 2009 and 2011. Of those, 506 patients had residual disease after neoadjuvant chemotherapy: 221 women had ypT1 disease, 138 had ypT2 disease, 97 ypT3 disease, and 73 ypT4 disease.
When the investigators plotted clinical outcomes by residual tumor size, they saw that the ypT1-2 patients and ypT3-4 naturally separated, Kern told OT. Of the women in the ypT1-2 group, 66.5 percent were disease-free at two years, compared with 22.8 percent of patients with ypT3-4 disease. “This is absolutely a disaster,” he said, regarding the ypT3-4 group.
Women with smaller-volume residual disease also had longer overall survival. Specifically, 79 percent of women in the ypT1-2 group remained alive at two years, compared with 60 percent of women with ypT3 and 68 percent of women with ypT4 disease.
He noted that until now, researchers looked at pathological response in a dichotomous way—either a complete response or a non-complete response. And there were just two survival curves—one for each of those response groups—published by Cornelia Liedtke et al in the Journal of Clinical Oncology in 2008 (26:1275-1281). (Liedtke is also a coauthor on the current study.)
“I always wondered if it was black and white,” Kern said. “If you have a patient whose residual tumor is 3.5 cm after chemotherapy; you have another patient, with residual tumor of 8 mm—they both have the same fate, according to the Liedtke et al paper, which is one of the most cited publications, in oncology.”
Based on his analysis though, he is clear that size does matter, he said.
The size of the study population was unusually large for a triple-negative cohort and that was a strength of the study, according to Melinda Telli, MD, Assistant Professor of Medical Oncology at Stanford University, who talked about the work during a poster discussion session. On the other hand, she said, two years was a relatively short follow-up, even for women with this type of breast cancer. Moreover, she said, Kern and colleagues did not include other prognostic factors in their analysis, which would have strengthened the work.
“In my research and clinical practice, I find this residual cancer burden index particularly helpful when thinking about prognosis for patients who have residual disease after primary chemotherapy,” Telli said, referring to a slide showing the residual disease burden calculator on the MD Anderson Cancer Center website. “This was an index developed by Fraser Symmans and colleagues, which set out to try to stratify responses beyond pCR and non-pCR.”
The risk calculator takes into account primary tumor bed size, overall percent cellularity, percentage of disease that is in situ, the number of positive nodes, and the diameter of the largest axillary metastasis. Based on those features, the calculator places each patient into one of four risk categories, from RCB-0, which is equivalent to pathological complete response, to RCB-III, which is extensive residual disease.
The calculator holds up for triple-negative disease, Telli said, and provides good separation between disease-free survival curves for the four risk groups.
To illustrate the point, she showed an example from her own practice. The patient initially presented with a T3 tumor, over 8 cm in size. The patient had a clinically complete response to neoadjuvant chemotherapy, but the post-surgery pathology report indicated that she still had T3 disease, with a 5 cm tumor remaining. When Telli requested a second pathology review, the pathologist reported that most of the tumor bed was scar tissue with only one percent cellularity. Putting that information into the risk calculator, the patient was put into the low-risk category with minimal residual disease, RCB-I.
“I think the point that needs to be made is that in this study, the patients with RCB-I, minimal residual disease, do have the same favorable prognosis as those who have an RCB of 0 [complete pathological response],” she said.
“I think size does matter, but so do other factors, including percent cellularity and nodal status,” she concluded. “I think these do need to be considered when thinking about prognosis in these patients.”
The meeting is co-sponsored by the American Society of Breast Disease, American Society of Breast Surgeons, American Society of Clinical Oncology, American Society for Radiation Oncology, National Consortium of Breast Centers, and Society of Surgical Oncology.© 2012 Lippincott Williams & Wilkins, Inc.
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