Pathologic Complete Response Yields Long-term Benefits in Meta-analysis  

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Breast cancer patients who achieve a pathologic complete response to neoadjuvant therapy have more favorable outcomes than those who do not, according to a meta-analysis of neoadjuvant trials presented at the 2012 San Antonio Breast Cancer Symposium.1

Patients who achieved a pathologic complete response had a 52% reduction in the probability of an event (P < .001) and a 64% reduction in the probability of death (P < .001), in the meta-analysis of the Collaborative Trials in Neoadjuvant Breast Cancer (CTNeoBC) presented by Patricia Cortazar, MD, Clinical Team Leader for the Breast Oncology Group of the U.S. Food and Drug Administration.

“Pathologic complete response is a proposed surrogate endpoint for predicting long-term clinical benefit on endpoints such as disease-free survival, event-free survival, or overall survival. A meta-analysis has been needed to establish the magnitude of pathologic complete response improvement on a trial level that results in improved disease-free survival,” said Dr. Cortazar.

The meta-analysis included 12 randomized controlled trials of neoadjuvant systemic therapy, including ECTO, EORTC 10994/BIG 1-00, GeparDuo, GeparQuattro, GeparTrio, GeparTrio-Pilot, NOAH, NSABP B18, NSABP B27, PREPARE, and TECHNO. The total population included 12,993 patients. Trials were included if pathologic complete response was clearly defined, all the necessary data were collected, and data on event-free and overall survival with long-term follow-up were available.

Three definitions of pathologic complete response, and the percentage of patients achieving them, were as follows:

  • ypT0, ypN0: Absence of invasive cancer in the breast and axillary nodes, and absence of ductal carcinoma in situ (DCIS) (13%)
  • ypT0/is, ypN0: Absence of invasive cancer in the breast and axillary nodes; DCIS is allowed (18%)
  • ypT0/is: Absence of invasive cancer in the breast regardless of nodal involvement; DCIS is allowed (22%) 

The achievement of a pathologic complete response was positively associated with more favorable long-term outcomes, including event-free and overall survival, Dr. Cortazar reported.

“The more favorable outcomes following pathologic complete response occurred regardless of whether DCIS was present or absent,” she said.

Eradication of tumor from both the breast and the lymph nodes was better associated with improved event-free and overall survival than eradication from the breast alone. For consistency, a standard pathologic complete response definition should be used in future trials, preferably ypT0ypN0 or ypT0/isypN0, she suggested.

Results by Breast Subtype

The achievement of pathologic complete response was highly variable by tumor subtype, with aggressive tumor subtypes more highly associated with event-free survival than smaller, less aggressive tumors. Pathologic complete responses were uncommon in patients with low-grade hormone receptor–positive tumors (7%) and more common among tumors that were high-grade hormone receptor–positive (16%), triple-negative (34%), hormone receptor–positive/HER2-positive (30%), and hormone receptor–negative/HER2-positive (50%).

The hazard ratios (HR) for event-free survival by subtypes, when pathologic complete response was achieved, were as following:

  • Hormone receptor–positive patients: HR = 0.49 (P < .001)
  • Hormone receptor–positive grade 3 patients: HR = 0.27 (P < .001)
  • Hormone receptor–positive grade 1/2: HR = 0.63 (P = .07)
  • HER2-positive patients: HR = 0.39 (< .001)
  • HER2-positive/hormone receptor–positive patients: HR = 0.58 (P = .001)
  • HER2-positive/hormone receptor–negative: HR = 0.25 (P < .001)
  • Triple-negative: HR = 0.24 (< .001)

Among HER2-positive patients, the association between pathologic complete response and risk reduction was enhanced with trastuzumab (Herceptin) treatment. In HER2-positive/hormone receptor–negative patients, hazard ratios associated with pathologic complete response were 0.35 (< .001) without trastuzumab and 0.15 (< .001) with trastuzumab treatment.

The magnitude of pathologic complete response improvement that predicts long-term clinical benefit could not be established, possibly due to low pathologic complete response rates, heterogeneous populations, and lack of targeted therapies in most trials, Dr. Cortazar said. ■

Disclosure: Dr. Cortazar reported no potential conflicts of interest.


1. Cortazar P, Zhang L, Untch M, et al: Meta-analysis results from the Collaborative Trials in Neoadjuvant Breast Cancer. 2012 San Antonio Breast Cancer Symposium. Abstract S1-11. Presented December 5, 2012.

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