Neoadjuvant systemic therapy includes neoadjuvant chemotherapy, endocrine therapy and molecular targeted drug therapy, and it has been 35 years since the first neoadjuvant chemotherapy was used for inoperable, locally advanced breast cancer in 1973.
Especially in recent years, with the emergence of new drugs for breast cancer, neoadjuvant chemotherapy, endocrine therapy and molecular targeted therapy have received more extensive attention and discussion, but to date, there are still unclear issues in the field of neoadjuvant therapy, such as neoadjuvant treatment indications, neoadjuvant treatment protocols, neoadjuvant treatment time frame, neoadjuvant efficacy evaluation system, and postoperative follow-up treatment options after neoadjuvant. Following the discussion of neoadjuvant systemic therapy by the members of the International Breast Cancer Expert Group from Europe and the United States in Germany in 2006, the members of the International Breast Cancer Expert Group from the United States, Germany, Italy, and the United Kingdom gathered again in the United States in 2007 to discuss many issues in the field of neoadjuvant therapy and to form the latest consensus. In this article, we will introduce and analyze the latest consensus of the international breast cancer expert group.
I. About neoadjuvant chemotherapy
1. Objectives of neoadjuvant chemotherapy
Traditional neoadjuvant chemotherapy includes the following goals.
(1) To reduce the clinical stage, increase the rate of surgery or breast-conserving surgery, and make the choice of treatment more flexible after neoadjuvant chemotherapy;
(2) To reduce the chance of tumor cell dissemination during surgery through preoperative systemic chemotherapy;
(3) In vivo drug sensitivity experiments, which provide important guidance for further drug therapy. In recent years, as the results of the neoadjuvant chemotherapy NSAB-BP B27 trial showed that breast cancer patients who achieved pathological complete remission after neoadjuvant chemotherapy could achieve higher overall survival.
Therefore, the pursuit of complete pathological remission with neoadjuvant chemotherapy should be the primary goal of neoadjuvant chemotherapy, and also the most important trial goal
2.Population for neoadjuvant chemotherapy
For patients with inoperable locally advanced breast cancer, it is now a consensus in the industry to receive neoadjuvant chemotherapy. In 2006, the international expert group concluded that neoadjuvant chemotherapy can be considered for all patients with early stage breast cancer who need to receive adjuvant chemotherapy.
The current NCI expert group’s opinion is that neoadjuvant chemotherapy has not shown any survival advantage over conventional chemotherapy for operable breast cancer. However, it provides more options for surgical procedures, and the proportion of breast-conserving surgery has increased significantly, while the slightly increased rate of local recurrence with a hazard ratio of 1.2 cannot be ignored. The evaluation of the efficacy of neoadjuvant chemotherapy is of great value to the prognosis of patients and the adjustment of treatment strategy that adjuvant chemotherapy cannot provide.
3.Neoadjuvant chemotherapy regimen
As for the choice of neoadjuvant chemotherapy regimen, the current regimen containing anthracyclines and paclitaxel has been widely accepted by the industry, and the two-drug combination regimen of anthracyclines + paclitaxel is mostly chosen in China, and the pathological pCR rate has increased from about 10% in the anthracycline-based regimen to about 20%. However, this expert group for neoadjuvant chemotherapy regimen selection, it is recommended that unless the tumor is large or clinical trial studies, the standard regimen recommendation for adjuvant chemotherapy should become the standard recommendation for neoadjuvant chemotherapy regimen.
4.Switching of neoadjuvant chemotherapy regimen
The GEPARTRIO trial reported results in this area. After breast cancer patients received two cycles of TXT+ADM+CTX neoadjuvant chemotherapy, 31% of patients with an efficacy rating of SD were randomized to two groups receiving 4 cycles of the original regimen, and 4 cycles of NVB+Hiroda regimen neoadjuvant chemotherapy, respectively.
A similar study was conducted in the Aberdeen trial. Breast cancer patients were evaluated for efficacy after receiving 4 cycles of neoadjuvant CTX+VCR+ADM+PDN (CVAP) chemotherapy. Patients with SD or PD efficacy were switched to TXT for 4 cycles, and the PCR rate was found to be less than 2% in this group. However, for patients with PR or CR efficacy, one group continued the original regimen for 4 cycles and one group was switched to TXT for 4 cycles, and the results showed that the patients had PCR rates of 15.4% and 30.8%, respectively, with a doubling of PCR in the switch group. Further follow-up also revealed that initial evaluation of effective patients, DFS and OSC, were significantly higher in the VAP/TXT group compared to the CVAP group. From the above two studies, the choice of neoadjuvant chemotherapy regimen is very important for the efficacy, and patients with operable PD should receive local treatment as soon as possible, but patients with inoperable PD may be considered for clinical trial studies. For patients with effective 4-cycle treatment, switching non-cross-resistance regimen is more effective and should be a better choice.
5.Follow-up treatment after surgery after neoadjuvant chemotherapy
After neoadjuvant chemotherapy, patients will generally receive surgery, radiotherapy, endocrine therapy, and molecular targeted therapy according to their condition. Whether it is necessary for patients to receive further chemotherapy after surgery has always been a concern for both doctors and patients. A study from MD Aderson Cancer Center in the United States evaluated this issue.
Patients were treated with surgery after neoadjuvant CVAP chemotherapy. 106 patients with residual tumor lesions larger than 1 cm were randomly divided into two groups, one group continued adjuvant chemotherapy with the original regimen and one group received adjuvant chemotherapy with VLB+MTX+CF, and the results showed that the DFS was slightly better in the switch regimen group, but there was no statistical difference. It is currently believed that after receiving a standard course of neoadjuvant chemotherapy, patients should not be given additional postoperative follow-up chemotherapy. However, clinical trial studies of complementary cross-resistance regimens, angiogenesis inhibitors, high-dose bisphosphonates, tumor vaccines and other new classes of biological agents are encouraged.
II. Neoadjuvant endocrine therapy
Neoadjuvant endocrine therapy, like neoadjuvant chemotherapy, has the same goals when applied to breast cancer patients and has attracted a lot of attention in recent years. A recent study from Russia compared the efficacy of neoadjuvant chemotherapy and neoadjuvant endocrine therapy in postmenopausal, receptor-positive breast cancer patients. A total of 121 patients were randomized to receive neoadjuvant chemotherapy with paclitaxel + ADM in 62 cases and neoadjuvant endocrine therapy in 59 cases, 30 of which received ranelastine and 29 of which received exemestane.
The clinical efficiency was found to be similar in the two groups, and the neoadjuvant endocrine therapy group had a slightly higher proportion of breast preservation with a median follow-up of 34 months, with no difference in the local recurrence rate between the two groups. In terms of toxicity, endocrine therapy had more advantages. This pilot study enlightens us that neoadjuvant endocrine therapy is by no means limited to a second option for patients who refuse neoadjuvant chemotherapy.
Neoadjuvant endocrine therapy options
Current neoadjuvant endocrine therapy drug options include triamcinolone acetonide, third-generation aromatase inhibitors, the former primarily for premenopausal patients and the latter primarily for postmenopausal patients. The differences in the efficacy of these drugs have been the subject of a number of studies. The code P024 trial compared the results of letrozole with TAM neoadjuvant endocrine therapy for inoperable or locally advanced breast cancer. The entire group of 337 patients was randomized into two groups and treated for 4 months. The results found clinical investigation efficiency of 55% and 36%.