pCR shows Limited Power for Breast Cancer Survival Predictions

The prognostic value of a pathological complete response in individual patients does not translate to clinical trial outcomes

medwireNews: Pathological complete response (pCR) significantly predicts long-term outcomes for individual breast cancer patients, especially those with aggressive disease, the results of the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC) pooled analysis confirm.

But the research published in The Lancet was unable to demonstrate in trial-level analysis that pCR – which is used as a marker of efficacy in accelerated drug approval applications – significantly predicted event-free survival (EFS) or overall survival (OS).

The study “emphasises the challenges associated with interpretation of neoadjuvant trial results,” say Lisa Carey (University of North Carolina, Chapel Hill, USA) and Eric Winer (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) in an accompanying comment.

They suggest that an agent may have to achieve a large increase in the rate of pCR before survival benefits will be seen, noting that tumour subtype and other factors will also alter the relationship between intermediate and long-term outcomes.

The CTNeoBC pooled data from 12 international trials that included at least 200 primary breast cancer patients who were given chemotherapy before surgery and had a median follow-up of at least 3 years.

Overall, pCR, EFS and OS data were available for 11,955 patients and responder analysis showed that the optimal definition of pCR was eradication of both breast and lymph node disease. Patients who MET this criteria had significantly better EFS and OS than those who did not, with hazard ratios of 0.44 and 0.36, respectively.

Using this definition of pCR, Patricia Cortazar, from the US Food and Drug Administration, and co-authors examined the impact of breast cancer subtypes on the relationship between pCR and survival and found pCR as a marker for survival outcomes was strongest in patients with aggressive subtypes of breast cancer.

In particular, the association was strongest in patients with triple-negative disease, those with high-grade, hormone receptor-positive, HER2-negative tumours, and patients with hormone Receptor-negative, HER2-positive cancer.

When assessing the impact of pCR on trial results, however, there was only a weak association with EFS and OS, which the researchers believe may be due to the breast cancer trials including a heterogeneous population of tumour subtypes and the small number of studies that used chemotherapy targeted to a tumour subtype.

“In view of the substantial improvements in survival for individual patients who attain [pCR], we believe that if a novel agent produces a marked absolute increase in frequency of [pCR] compared with standard therapy alone in the intention-to-treat population, that agent could also be reasonably likely to result in long-term improvements in EFS or OS,” they write.

“In our future analyses (with genomic assays to better characterise subgroups and including additional anti-HER2 trials), we will investigate the importance of [pCR] in defined subsets and assess other promising surrogate endpoints.”


Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet; Advance online publication 14 February 2014. doi:10.1016/S0140-6736(13)62422-8
Carey L and Winer E. Defining success in neoadjuvant breast cancer trials. Lancet; Advance online publication 14 February 2014. doi:10.1016/S0140-6736(14)60034-9 Link

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