SGBCC International Dialogue| Dr. Li Zhu & Dr. Giuseppe Curigliano Discuss the Need for Adjuvant Therapy After Achieving pCR in Neoadjuvant Treatment

Neoadjuvant therapy has become an integral part of breast cancer treatment, with its increasing application in clinical practice. However, improving the effectiveness of neoadjuvant therapy and optimizing subsequent treatment strategies is a complex issue to consider. At the 18th St.Gallen Breast Cancer Conference (SGBCC 2023), a debate titled “If you achieve pCR after neoadjuvant, do you need adjuvant therapy?” drew global expert attention. Oncology Frontier had invited Dr. Li Zhu from Shanghai Jiao Tong University School of Medicine, First People’s Hospital, and Dr. Giuseppe Curigliano from the University of Milan School of Medicine to engage in an in-depth discussion on this topic.

Oncology Frontier : When a patient achieves pCR (pathological complete response) after neoadjuvant therapy, do they still need adjuvant therapy? Could you please share your perspectives?

Dr. Giuseppe Curigliano：My perspective is that if HER2-positive breast cancer patients achieve pCR after neoadjuvant therapy, they should proceed with completing two cycles of chemotherapy and one full year of targeted therapy. The question arises whether we should use trastuzumab alone or combine it with pertuzumab as part of the targeted therapy regimen. For patients with locally advanced breast cancer at baseline, I recommend the combination of trastuzumab and pertuzumab in the targeted therapy regimen. So, for a patient with cT3N2M0, they should receive the combination of trastuzumab and pertuzumab for a full year. For a patient with cT2N0M0, targeted therapy with trastuzumab alone for one year may suffice.

Dr. Li Zhu : Regarding the question of whether adjuvant therapy is still necessary after achieving pCR in neoadjuvant treatment, a simple “yes” or “no” answer may be too simplistic. We need to consider different scenarios based on the evidence from evidence-based medicine. From subgroup analyses of the Brightness clinical trial, we can see that the overall survival (OS) for triple-negative breast cancer is significantly worse than for luminal and HER2-positive subtypes, even when pCR is achieved. For patients with initial tumor staging of T3, T4, or lymph node-positive disease who achieve pCR, their OS is also worse. Additionally, in large meta-analyses like CTneoBC, it’s observed that in the HER2-positive subgroup, patients with initial staging of T3, T4, or clinical lymph node-positive disease have worse event-free survival (EFS) even when achieving pCR.

So, from the evidence presented, it’s clear that not all patients who achieve pCR necessarily experience satisfactory EFS or OS outcomes. In the current landscape of breast cancer molecular subtyping, treatment decisions must be tailored to different molecular subtypes. For HER2-positive breast cancer patients who have undergone neoadjuvant chemotherapy and achieved pCR, we still apply the principle of individualized treatment. For patients initially diagnosed as lymph node-negative, most experts would recommend considering continuing with single-agent targeted therapy, as confirmed in the Neosphere study. For patients at moderate or high risk or those with lymph node-positive disease, a full year of dual-targeted therapy can still be an option. However, for patients with exceptionally high-risk factors or a substantial tumor burden, the AGO guidelines recommend intensified adjuvant therapy with neratinib after achieving pCR.

In addition to the evidence from evidence-based medicine, we also have biomarkers that can predict patient outcomes. Recent studies suggest that for patients who achieve pCR after neoadjuvant therapy, assessing whether their ctDNA (circulating tumor DNA) is positive can help predict prognosis.

In summary, this question cannot be answered with a simple “yes” or “no.” It requires consideration of different molecular subtypes, the baseline tumor burden before neoadjuvant treatment, dynamic changes in ctDNA, and new biomarkers to guide decisions on which patients need adjuvant therapy after achieving pCR and which do not.

For luminal breast cancer, if pCR is achieved after neoadjuvant chemotherapy, adjuvant endocrine therapy should definitely be considered. While chemotherapy may not be necessary for those who achieve pCR, there is currently insufficient evidence to answer whether the addition of CDK4/6 inhibitors to adjuvant endocrine therapy is necessary for patients who achieve pCR, especially if ER and PR expression is low (<10%). This subset of patients is closer to the Basal-like subtype in the PAM 50 molecular classification.

For triple-negative breast cancer, treatment decisions are more complex. Immunotherapy has become an important component of neoadjuvant treatment for triple-negative breast cancer. Therefore, when pCR is achieved with immunotherapy in combination with chemotherapy, the question of whether to continue immunotherapy remains a topic of debate in clinical practice. I believe that the OptimILE-pCR clinical study will provide answers to this question in the near future. The study includes patients who have received at least six cycles of chemotherapy and immunotherapy and, after achieving pCR with immunotherapy, one group continues with one year of immunotherapy, while the other group is observed, and their three-year EFS outcomes are compared. I am confident that the data from this study will address our current uncertainties.