5MO - Evaluation of pathological complete response (pCR) after neoadjuvant chemo-radiation therapy for primary breast cancer (JCOG0306A1)

Background

The JCOG0306 was a phase II study of preoperative sequential chemoradiation therapy for the nonsurgical treatment of early breast cancer. In JCOG0306 trial, we employed the representative cut surface sampling (R method) for evaluating pathological therapeutic effect and pathological complete response (pCR) rate. In addition, therapeutic effect was also evaluated for whole tumor bed sampling in case the primary tumor grossly disappeared by referring to the pretreatment imaging findings (T method). pCR was evaluated by central pathology review and defined as disappearance of invasive carcinoma component.

Methods

We compared pCR rates and prognostic significance of pCR between R and T methods to validate the use of R method in the trial.

Results

Totally, 103 (95%) of 108 invasive cancer patients enrolled were evaluated. Median age was 51 (23-69), cStage I/IIA/IIB/IIIA were 1/50/48/4, and ER and HER2 positive were 63 and 33, respectively. %pCR were 37.9% (n = 39) by R method and 24.3% (n = 25) by T method, and their concordance rate was 86.4% (89/103). Almost all discordant cases were histologically Grade 2b (only a small number of invasive cancer cells remained). With a median follow up period of 11.6 years, among node-negative patients, OS significantly differed between pCR and non-pCR patients (10yOS: pCR 94.3% vs. non-pCR 75.7%; 10yrRFS: 90.9% vs. 66.6%, p = 0.047), whereas there was no significant difference by T (10yOS: 95.2% vs. 78.7%, p = 0.13). When pCR and Grade 2b patients were combined, pCR/Grade 2b patients and others showed significantly different clinical outcomes for OS and RFS by both R and T methods.

Conclusions

R method provided stronger stratification of prognosis between pCR and non-pCR patients than T method and the use of R method was proved to be reasonable for the evaluation of therapeutic effect. The combination of pCR and Grade 2b appeared to be more sensitive to identify the patient group who received chemoradiation therapy and showed better clinical outcome in both R and T methods.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

the National Cancer Center Research and Development Fund (29-A-3).

Disclosure

T. Shien: Honoraria (self): Chugai; AstraZeneca; Novartis; Kirin; Allergan; Pfizer; Honoraria (self): Daiichi Sankyo; Eizai. N. Hayashi: Honoraria (self): Chugai; Novartis; AstraZeneca; Kirin; Genomic Health; Allergan; Devixcor Japan; Pfizer. N. Masuda: Honoraria (self), Research grant/Funding (self): Chugai; AstraZeneca; Pfizer; Eli-Lilly; Eisai; Takeda; Research grant/Funding (self): MSD; Kyowa-Kirin; Novartis; Nihon-Kayaku; Daiichi Sankyo. All other authors have declared no conflicts of interest.