What is rcb in breast cancer?

For some people with breast cancer, treatment begins with chemotherapy, HER2-targeted therapy, immunotherapy and/or hormone therapy, rather than surgery. This is called neoadjuvant therapy or preoperative therapy.

Neoadjuvant therapy may shrink the cancer in the breast and/or lymph nodes in the underarm area (axillary lymph nodes). If it shrinks the tumor enough, a lumpectomy may become an option to a mastectomy. In some cases, response to neoadjuvant chemotherapy can help guide treatment after breast cancer surgery.

Information on a pathology report is a bit different for people who get neoadjuvant therapy compared to those who get surgery as their first treatment. This page describes pathology reports, including the information used in breast cancer staging, for people who get neoadjuvant therapy.

Breast cancers treated with neoadjuvant therapy are staged a bit differently than those treated with surgery first.

Before neoadjuvant therapy begins, the pre-treatment stage of your breast cancer may be done. If so, pre-treatment stage is determined using imaging (such as mammograms) and findings from a physical exam of the breast. This is called clinical prognostic stage.

After surgery, the stage of your breast cancer is determined using pathology information from the tissue removed during surgery. The pathologic stage after neoadjuvant therapy gives the most information on your prognosis (chances for survival).

The main method of pathologic staging for breast cancer is the TNM system which stands for (Tumor size, lymph Node status and Metastases).

When TNM is used after neoadjuvant therapy, you’ll see a “y” before the T and N measures on your pathology report. Otherwise, the categories are the same as those for tumors not treated with neoadjuvant therapy. A “p” means a pathologist took the measurement from the tissue removed during surgery.

ypT = Tumor stage after neoadjuvant therapy

ypN = Lymph node status after neoadjuvant therapy

Metastatic status is determined before treatment begins.

M0 = No metastases

M1 = Metastases

Neoadjuvant therapy is only used to treat non-metastatic breast cancer. So, if you get neoadjuvant therapy, you should see “M0” on your pathology report.

Neoadjuvant therapy may shrink a tumor enough so a lumpectomy becomes an option to a mastectomy.

Sometimes, imaging shows there’s no cancer left in the breast after neoadjuvant therapy. However, you will still have breast surgery.

There may be some cancer left in the tumor bed (the original site of the breast cancer) that’s too small to see on imaging. So, tissue from the tumor bed must be removed and checked to be sure.

After surgery, a pathologist studies the breast tissue removed. The pathologist’s findings are used to determine how well the breast cancer responded to neoadjuvant therapy. This information is included on your pathology report.

The breast cancer’s response to neoadjuvant treatment gives useful information about prognosis (chances for survival).

Sometimes, the pathologist’s exam shows no sign of cancer in the breast or axillary lymph nodes. This is called a pathologic complete response (pCR) and means the neoadjuvant therapy got rid of all the invasive breast cancer.

A pCR can give some information about prognosis (chances for survival), but it doesn’t usually change your treatment plan.

Although a pCR is encouraging, it doesn’t mean the cancer will never return. And many people who don’t have a pCR will still do very well.

If you have a pCR, it will be noted on your pathology report.

Learn more about pathologic complete response.

Any invasive breast cancer that remains in the breast or axillary lymph nodes after neoadjuvant therapy is called residual breast cancer. Some people have some residual breast cancer after neoadjuvant therapy.

Your pathology report will include whether or not residual invasive breast cancer was found in the breast and/or lymph nodes and the size of any residual cancer.

Sometimes, information about residual cancer burden (RCB) is included on your pathology report.

An RCB score is determined using information on the size of the tumor and the extent of tumor cells in the breast and axillary lymph nodes after neoadjuvant therapy.

The higher the RCB score, the more residual invasive breast cancer there is in the breast and lymph nodes:

Learn more about the contents of a pathology report.

You may have had tests done on the pre-treatment biopsy tissue (the tissue that diagnosed the breast cancer), such as tests for hormone receptors status and HER2 status. Sometimes, these tests are repeated on the tissue removed during breast cancer surgery to confirm the test results are the same.

It’s not clear whether repeating these tests is helpful to guide prognosis (chances for survival) or treatment.

Other information on a pathology report is the same for people who have neoadjuvant therapy and those who have surgery as their first breast cancer treatment.

Learn more about the contents of a pathology report.

Updated 12/20/22

The Residual Cancer Burden (RCB) index has been developed in 2007 by Symmans and colleagues from the M.D. Anderson Cancer Center (MDACC) [3] to quantify residual disease following NAC. The RCB index combines pathological findings in the primary tumor bed and the regional lymph nodes to calculate a continuous index.

By Caroline Helwick January 25, 2020

Residual cancer burden after neoadjuvant chemotherapy can accurately predict disease recurrence and survival across all breast cancer subtypes, according to the findings from a meta-analysis presented at the 2019 San Antonio Breast Cancer Symposium by W. Fraser Symmans, MD, Professor and Director of Research Operations in Pathology at The University of Texas MD Anderson Cancer Center, Houston.1

This is not the first study to show residual cancer burden to be an independent factor for prognosis after neoadjuvant chemotherapy. This study, however, goes a step further in estimating the long-term prognosis for each class of residual cancer burden across breast cancer subtypes.

“The most important conclusion is that there is a strong potential to calibrate an individual’s [residual cancer burden] index score to her residual prognostic risk,” Dr. Symmans said. “There is a generally linear relationship between [residual cancer burden] index value and the log of risk.”

Calculating Residual Cancer Burden

“This is really about organizing the workflow in pathology to standardize how we evaluate response after neoadjuvant treatment,” Dr. Symmans said. He explained that pathologists calculate residual cancer burden from multiple factors: primary tumor area, percentage of the tumor area that is invasive cancer, and extent of lymph node involvement. Investigators at The University of Texas MD Anderson Cancer Center put these factors together to develop a residual cancer burden calculator, which computes an index and allocates a classification of pathologic complete response (www.mdanderson.org/breastcancer_RCB). A value of 0 equates to a pathologic complete response. This is then categorized into one of the following three classes: RCB-I (minimal burden), RCB-II (moderate burden), and RCB-III (extensive burden).

“The basic principle is that we estimate the area that still contains residual disease, map that area to the slides that we’ll be looking at under the microscope, and create an image so that we can reconstruct it and be able to determine what area still contains actual cancer,” Dr. Symmans explained. “Then, we combine that with the fraction of that area that still contains invasive cancer cells, as well as the number of positive lymph nodes and the size of the largest metastasis. This is just organizing what we would otherwise report in pathology, but we’re doing it in a quantitative and standardized manner.”

The online calculator page receives about 16,000 visits per month, “so it’s being used out there,” he noted. The website offers instructional videos, protocols, illustrations, and diagrams as resources for the pathologists who use it.

Pooled Data

The pooled analysis came from the I-SPY Clinical Trials Consortium, involving 12 institutions or clinical trials and encompassing 5,160 patients. The study examined the relationship between the continuous residual cancer burden index and event-free survival, as well as distant relapse–free survival for four breast cancer phenotypes: hormone receptor–negative/HER2-negative (triple-negative), hormone receptor–negative/HER2-positive, hormone receptor–positive/HER2-positive, and hormone receptor–positive/HER2-negative. For each subtype, a multivariate analysis adjusted for patient age, tumor size, nodal status, and grade.

Relationship Between Residual Cancer Burden and Prognosis

The residual cancer burden index was tightly associated with both event-free and distant disease–free survival. This finding was consistent across 12 clinical sites and all cancer subtypes.

“The most interesting result, in my opinion, is that you see a log-linear relationship for the [residual cancer burden] index score and survival,” Dr. Symmans said. “The implication is that you can take an individual patient’s score representing how much residual cancer she has and calibrate that to an accurate estimate of her risk over time.”

A pathologic complete response (RCB-0) was most likely to be achieved by hormone receptor–negative/HER2-positive patients (69%) and least likely by the hormone receptor–positive/HER2-negative group (11%); the triple-negative group (43%) and hormone receptor–positive/HER2-positive group (38%) fell in between.

The residual cancer burden index values were associated with 5-year and 10-year event-free survival, as shown in Table 1.

Elaborating on what emerged from the four subgroups, Dr. Symmans said that in the hormone receptor–negative/HER2-positive group, the 69% rate of pathologic complete response was “striking” and “illustrates how effective these current [HER2-targeted] treatments are.” The 20% of patients who were classified as RCB-II and RCB-III had significantly worse survival than the others. “It’s a small quintile of patients that’s still at fairly substantial risk.”

He added, “In the hormone receptor–positive/HER2-negative breast cancer group, where there is still a bit of confusion about whether or not chemotherapy can help patients, we see that the extent of residual disease is strongly prognostic.”

In the subgroup with hormone receptor–positive/HER2-negative disease, he continued, “you can see that there’s clearly an effect on prognosis from the chemotherapy. However, the most prognostic aspect of the distribution of response is where there is the most residual disease—the RCB-III and RCB-II groups. Their long-term risk is still continuing beyond 10 years.”

The residual cancer burden index remained independently prognostic in multivariate models adjusting for patient age, grade, and clinical T and N stage at diagnosis. Its value was 1.93 in the triple-negative group, 2.04 in the hormone receptor–negative/HER2-positive group, 1.67 in the hormone receptor–positive/HER2-positive group, and 1.52 in the hormone receptor–positive/HER2-negative group. T4 tumors (and in the triple-negative group, also T3) remained independent predictors of prognosis as well.

Message to the Pathology Community

“Looking ahead, if we can standardize the reporting of residual cancer burden, that will only improve its usefulness in determining long-term prognosis,” Dr. Symmans emphasized. “This study is important in showing the generalizability of residual cancer burden, and it’s of sufficient size to generate the evidence to convince the pathology community to change the way we do things.”

Dr. Symmans noted that synoptic reporting is a requirement in oncology, but there is only one synoptic report for invasive cancer—one that is designed for a surgery-first examination. What’s lacking is a neoadjuvant synoptic report that specifically addresses the needs in interpreting a post-neoadjuvant response, he said. “The neoadjuvant model is increasingly related to precision medicine. We are standing at that transition point.” ■

DISCLOSURE: Dr. Symmans holds a patent for the method of calculating residual cancer burden. The residual cancer burden calculator and educational materials are freely and publicly available online. He is also cofounder, owns shares in, and is an unpaid scientific advisor for Delphi Diagnostics.

REFERENCE

1. Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis. 2019 San Antonio Breast Cancer Symposium. Abstract GS5-01. Presented December 13, 2019.

Several studies have demonstrated independent validation of the prognostic relevance of RCB post-neoadjuvant chemotherapy. The large, multicenter, pooled meta-analysis was done to determine estimates of long-term prognosis for each class of RCB across breast cancer subtypes to better inform patient outcomes.

RCB is evaluated through multiple factors, including primary tumor size, percentage of the tumor that is invasive versus in situ, and lymph node involvement, said W. Fraser Symmans, MD, a professor and director of research operations in the Department of Pathology at The University of Texas MD Anderson Cancer Center, in a press conference during the meeting.

An RBC calculator, hosted by The University of Texas MD Anderson Cancer Center, computes an RBC index and allocates a classification of pathologic complete response (pCR), with 0 equating to a pCR. That is then categorized into 1 of the following 3 classes: RCB-I (minimal burden), RCB-II (moderate burden), and RCB-III (extensive burden).

"The basic principle is that we estimate the area that still contains residual disease, map that area to the slides that we’ll be looking at under the microscope, and create an image so that we can reconstruct it and be able to determine what area still contains actual cancer," explained Symmans.

"Then, we combine that with the fraction of that area that still contains invasive cancer cells, as well as the number of positive lymph nodes and the size of the largest metastasis," he added. "This is just organizing what we would otherwise report in pathology, but we’re doing it in a quantitative and standardized manner."

For the analysis, investigators from the I-SPY Clinical Trials Consortium collected and reviewed subject-level RCB data, with relevant clinical and pathologic stage, tumor subtype and grade, demographic, treatment, and follow-up findings from a total of 12 institutions or clinical trials, encompassing a little over 5100 patients.

Using mixed effect Cox models, the relationship between the continuous RCB index and event-free survival (EFS) as well as distant relapse-free survival (DRFS) was evaluated; random RCB coefficients were incorporated to account for between-study heterogeneity. Furthermore, a multivariate analysis adjusted for age, T-category, nodal status, and grade was done within each breast cancer subtype. Results demonstrated that RCB index was tightly associated with both EFS and DRFS; this finding was consistent across 12 clinical sites and all 4 breast cancer subtypes, which included the following: hormone receptor (HR)—negative/HER2-negative, and HR-negative/HER2-positive, HR-positive/HER2-positive, and HR-positive/HER2-negative.

In the HR-negative/HER2-negative group (n = 1774), almost half of patients (43%) were classified as having a pCR, 12% as RCB-I, 33% as RCB-II, and 11% as RCB-III. At the 10-year follow-up, 14% of those in the pCR group either experienced a recurrence or had died versus 25%, 39%, and 75% of those in the RCB-I, RCB-II, and RCB-III groups, respectively.

In the HR-negative/HER2-positive group (n = 488/572), 69% of patients were classified as having experienced a pCR, “really illustrating how effective these current treatments are,” noted Symmans; 11% of patients were classified as RCB-1, 16% as RCB-II, and 4% as RCB-III. The 10-year EFS rate was highest in the pCR group at 93%, followed by 85% in the RCB-I group, 63% in the RCB-II group, and 60% in the RCB-III group.

"The 20% of patients [in the] RCB-II and RCB-III [groups are estimated to] have a significantly worse survival than the rest,” said Symmans. “Although this is a small quantile of patients, they still have really substantial risk."

With regard to the HR-positive/HER2-positive group (n = 756/858), 38% of patients were classified as having a pCR, 20% as RCB-I, 33% as RCB-II, and 8% as RCB-III. Nine percent of those in the pCR group either experienced a recurrence or had died versus 17% of the RCB-I group, 36% of the RCB-II group, and 55% of the RCB-III group at the 10-year follow-up.

“In the HR-positive/HER2-negative breast cancer group, where there is still a bit of confusion about whether or not chemotherapy can help patients with this type of disease, we see that the extent of residual disease is strongly prognostic,” stressed Symmans.

In the last group of patients with HR-positive/HER2-negative disease (n = 1957), 11% of patients were classified as having a pCR; furthermore, 11% of patients were classified as RCB-I, 53% as RCB-II, and 25% as RCB-III. With regard to 10-year EFS, the rate was 81% in the pCR group compared with 86%, 69%, and 52%, in the RCB-I, RCB-II, and RCB-III groups, respectively.

"Here, you can see that there’s clearly an effect on prognosis from the chemotherapy," said Symmans. "However, the most prognostic aspects of the distribution of response [is] when there’s the most residual disease—the RCB-III and RCB-II [groups]. That’s a long-term risk that’s still continuing beyond 10 years."

The RCB index remained prognostic in multivariate models adjusting for age, grade, and clinical T and N stage at diagnosis. The RCB index value for the HR-negative/HER2-negative subtype was 1.93 (1.74-2.13), 2.04 (1.65-2.53) in the HR-negative/HER2-positive subtype, 1.67 (1.42-1.97) in the HR-positive/HER2-positive subtype, and 1.52 (1.36-1.69) in the HR-positive/HER2-negative subtype, thus showing that the RCB index was independently significant in each of the subtypes.

"The most important conclusion is that there is a strong potential to calibrate an individual's RCB index score to her residual prognostic risk," said Symmans. "There is a generally linear relationship between RCB index value and the log of risk, and it is entirely feasible to have phenotype-specific calibration risk curves for use in the communication of risk and the interpretation of clinical trials."

One study limitation was that it included data from several institutions, and as such, there was some variation with regard to the clinical methods used, the handling of specimens, and other potential factors. Furthermore, some RCB data were collected prospectively and some were collected retrospectively.

"Looking ahead, if we can standardize the reporting of residual cancer burden, that will only improve its usefulness in determining long-term prognosis," concluded Symmans.2

References

1. Yau C, van der Noordaa M, Wei J, et al. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: a multi-center pooled analysis. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-01. bit.ly/2PmQvfn.

2. Residual cancer burden can predict outcomes for patients with any breast cancer type [news release]. San Antonio, TX: American Association for Cancer Research; December 13, 2019. bit.ly/34jF6RE. Accessed December 13, 2019.