By Dr. Shipra Gandhi
Roswell Park Comprehensive Cancer Center
Attainment of pathological complete response (pCR) of breast cancer is associated with improved long-term outcomes (event-free survival and overall survival) compared to patients with residual disease after neoadjuvant therapy (1). This is primarily true for TNBC and Her2-positive breast cancer but also for some luminal-B tumors. However, despite a pCR, 15-20% of patients relapse within five years.
In a recently published, interesting study by Huober et al. in NPJ Breast Cancer (2), pooled analysis of the five neoadjuvant GBG/AGO-B trials GeparTrio, GeparQuattro, GeparQuinto, GeparSixto, and GeparSepto to investigate factors predicting a relapse despite the fact that a pCR was conducted. This study analyzed around 1800 breast cancer patients with pCR after neoadjuvant chemotherapy, showing that positive lymph nodes, cT3/T4, and lobular histology predict a worse prognosis. This analysis highlights that the tumor stage at the time of diagnosis is important. The authors discuss that this may be because tumors with a higher stage at diagnosis may have more circulating tumor cells (CTCs) whose presence before rather than after completion of neoadjuvant treatment is associated with worse clinical outcomes.
Other studies (3) have shown that lack of ctDNA clearance after neoadjuvant therapy was a significant predictor of poor response and metastatic recurrence, while clearance was associated with improved survival even in patients who did not achieve pCR. Therefore, personalized monitoring with ctDNA may help pCR as a surrogate endpoint of survival.
The above studies show the importance of clinicopathologic factors in determining prognosis, how pCR may not always translate into improved clinical outcomes, and the utility of ctDNA monitoring. In the future, these factors may need to be considered to tailor post-neoadjuvant treatment appropriately.
(1) Cortazar, P. et al. “Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.” Lancet (London, England). 384, 164–172 (2014).
(2) Huober et al. “Identifying breast cancer patients at risk of relapse despite pathological complete response after neoadjuvant therapy.” NPJ Breast Cancer vol. 9,1 23. 7 Apr. 2023, doi:10.1038/s41523-023-00525-2
(3) Magbana et al. “Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response and survival.” Annals of oncology: official journal of the European Society for Medical Oncology vol. 32,2 (2021): 229-239. doi:10.1016/j.annonc.2020.11.007