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Residual Breast Cancer Tool Highly Prognostic After Neoadjuvant Tx

— Tumor burden calculator predicted long-term outcomes in all breast cancer subtypes

MedpageToday

SAN ANTONIO -- A residual cancer burden (RCB) calculator to assess neoadjuvant chemotherapy response proved to be an accurate and reliable predictor of long-term breast cancer outcomes, according to a large meta-analysis.

Pooling data on over 5,000 patients from a dozen sites, researchers were able to classify patients into three groups based on the degree of their remaining disease using the , and it maintained its accuracy across all breast cancer phenotypes.

"This is really about organizing the workflow in pathology to standardize the way we evaluate response after several months of neoadjuvant treatment," said W. Fraser Symmans, MD, of MD Anderson Cancer Center in Houston, said during a press conference at the San Antonio Breast Cancer Symposium (SABCS).

Seven fields are required to calculate the amount of remaining tumor burden -- dimensions of residual disease in the tumor bed, percentages of overall cancer cellularity and in situ disease, number of involved lymph nodes, and diameter of the largest metastasis -- and patients are then classified as having minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) disease burden based on a continuous index.

"There's no special testing here, this is just organizing what we would otherwise report anyway in pathology, but doing it in a quantitative and standardized manner," explained Symmans, a pathologist at MD Anderson who holds a patent on the RCB tool (he said it would remain free).

"Residual cancer burden was prognostic in each phenotypic subtype of disease," he said, adding that it works independently of pretreatment clinical and pathologic factors.

For HR-positive/HER2-negative patients, just 11% achieved pathologic complete response (pCR), while 11% were classified as RCB-I, 53% as RCB-II, and 25% as RCB-III. With 10 years of follow-up, event-free survival (EFS) rates for these groups were:

  • pCR: 81%
  • RCB-I: 86%
  • RCB-II: 69%
  • RCB-III: 52%

In HR-positive/HER2-positive disease, 38% had a pCR, while 20% were classified as RCB-I, 33% as RCB-II, and 8% as RCB-III. At 10 years of follow-up, these EFS rates were:

  • pCR: 91%
  • RCB-I: 83%
  • RCB-II: 64%
  • RCB-III: 45%

Patients with HR-negative/HER2-positive breast cancer achieved the highest pCR rates, at 69%, with 11% classified as RCB-I, 16% as RCB-II, and 4% as RCB-III. With 10 years of follow-up, EFS rates were:

  • pCR: 93%
  • RCB-I: 85%
  • RCB-II: 63%
  • RCB-III: 60%

For HR-negative/HER2-negative tumors, 43% achieved a pCR, while 12% were classified as RCB-I, 33% as RCB-II, and 11% as RCB-III. EFS rates at 10 years were:

  • pCR: 86%
  • RCB-I: 75%
  • RCB-II: 61%
  • RCB-III: 25%

A number of clinical trials are starting to use these RCB groups to test adjuvant treatments in patients who fail to achieve pCR following neoadjuvant therapy.

"RCB is really powerful because it helps us design the trials where we can minimize treatment on the patients that potentially don't need anymore and can maximize it on the patients that need a lot more," said SABCS press briefing moderator Virginia Kaklamani, MD, of UT Health San Antonio, who said she requests RCB for her patients despite the limited current applicability.

"In the triple-negative patients, I may consider giving capecitabine in the adjuvant setting or obviously enroll them in clinical trials," Kaklamani said. "In my HER2-positive patients, I will look at from the KATHERINE trial and look at the of the ExteNET trial to guide me. In the estrogen receptor-positive patients, I'm still waiting for results from other trials."

Co-author Laura Esserman, MD, MBA, of the University of California San Francisco, said the hope was that the results would change the Joint Commission standards for breast cancer staging.

"And we expect that that will happen on the basis of these results," she said, but she said it will be critical that there be training and a commitment to using the method in a consistent way.

"This study is very important to demonstrate generalizability and sufficient size and precision to generate the evidence to convince the pathology community to slightly change the way we do things," Symmans said.

More specifically, he noted that synoptic reporting for invasive cancer -- required for all cancers -- is designed for a surgery-first evaluation.

"We actually don't, at a national or international level, have a post neoadjuvant synoptic report that specifically addresses the needs of the interpretation of the post-neoadjuvant response, and if we can get to a point where we can bring about that change, then we can say what's evidence-based," he said.

For their study, Symmans and colleagues from the I-SPY Clinical Trials Consortium analyzed data on over 5,161 patients from 12 trials or cancer centers, which in part was cited as a limitation due to different collection methods. Also, some specimens were collected prospectively and some retrospectively.

The RCB tool proved prognostic for EFS and distant relapse-free survival. In multivariate analysis that included pretreatment pathological and clinical parameters, certain factors added additional risk for the different breast cancer subtypes, such as T4 disease across all, T3 in triple-negative disease, and positive lymph nodes and grade III disease for hormone receptor-positive/HER2-negative cancers.

Disclosures

The study was funded by the Department of Defense, the NIH, the Cancer Prevention Research Institute of Texas, and the Breast Cancer Research Foundation.

Symmans disclosed holding a patent on the residual cancer burden calculator.

Primary Source

San Antonio Breast Cancer Symposium

Yau C, et al "Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis" SABCS 2019; Abstract GS5-01.