To Use pCR, We Must First Define It
Pathological complete response can provide valuable information on survival in breast cancer, but is a standard definition within reach?
Roisin McGuigan |
A pooled analysis of the relationship between pathological complete response (pCR) and breast cancer has highlighted an important issue: different studies are using different definitions of pCR, making it tough to compare results and to understand its prognostic value.
The analysis was conducted by Collaborative Trials In Neoadjuvant Breast Cancer (CTNeoBC), an international breast cancer working group established by the US Food and Drug Administration (FDA). The study is believed to be the first to use primary source data to investigate the relationship between pCR, event-free survival (EF) and overall survival (OS) in breast cancer patients.
pCR refers to the eradication of cancer in response to therapy, but its definition remains unstandardized; an issue that the CTNeoBC working group set out to address (1).
The study looked at 12 international breast cancer trials (a total of 11,955 patients) and found several different definitions of pCR were used. CTNeoBC compared the most common three: absence of cancer in breast tissue and lymph nodes (ypT0 ypN0); absence of cancer in breast tissue and lymph nodes regardless of the presence of ductal carcinoma (ypT0/is ypN0); and absence of cancer in breast tissue alone (ypT0/is).
The study revealed that eradication of tumor from both breast tissue and lymph nodes had a stronger association with improved EFS and OS than did eradication from breast tissue alone. As such, they propose that pCR is defined as either ypT0/is or ypT0 ypN0 in future studies; they found that ductal carcinoma had no effect on outcome in the studies they analyzed.
A key objective for the team was to establish pCR as a surrogate endpoint for assessing long-term breast cancer outcomes – namely EFS and OS. Unfortunately, the trial was unable to validate pCR as a surrogate endpoint, which the authors admit was disappointing. “This was also surprising in view of the substantial improvements in survival for individual patients who attain pCR,” explains Patricia Cortazar, lead author of the research.
However, Cortazar remains positive, adding that the study does establish which pCR definitions best correlate to long-term outcomes – this may help to address the lack of standardization of pCR. They also found that individual patients who attain pCR have a 64 percent reduction in risk of death, compared with patients with residual tumor; the authors believe this confirms the prognostic value of pCR, which was found to be greatest in patients with aggressive tumor subtypes.
Perhaps pCR will eventually be established as a surrogate endpoint through further study. “We hypothesize that randomized trials of targeted agents in homogeneous tumor subtypes, with larger differences in pCR rates, will likely demonstrate a relationship between pCR and long-term outcome,” says Cortazar. “Analyses of additional trials in a targeted population will be needed to demonstrate whether or not there is a relationship between pCR and long-term outcome at a trial level.”
- P. Cortazar et al., “Pathological Complete Response and Long-Term Clinical Benefit in Breast Cancer: the CTNeoBC Pooled Analysis”, Lancet, 384, 164-72 (2014).