At this stage, the incidence of breast cancer occupies the first place among female tumors worldwide and is on the rise. 5% to 10% of breast cancer patients are diagnosed with advanced breast cancer (MBC) at the time of initial diagnosis, and a significant proportion of early-stage breast cancer patients will develop recurrent metastasis.
The factors influencing the occurrence of recurrence or distant metastasis of breast cancer: the main ones are as follows.
① Clinicopathological factors at the time of diagnosis, including larger lesions, high tissue grading, and increased risk of metastasis in patients with positive lymph nodes; the proportion of metastasis within 5 years in patients aged <40 years is 24%, much higher than that of 9% in patients over 40 years.
②Whether they received reasonable and regular adjuvant therapy;
③Patients with breast cancer aged <40 years, triple negative (TNBC), hormone receptor (HR) negative human epidermal factor receptor 2 (HER2) positive are more likely to develop visceral metastasis.
Prognosis of MBC.
(i) The prognosis is usually better for those who are younger, have limited lesions, and achieve complete remission with initial treatment;
②The prognosis is worse in the presence of visceral metastases compared to isolated chest wall or ipsilateral axillary lymph node recurrence, bone or soft tissue metastases;
③In terms of molecular typing, survival was longer for chemotherapy beneficiaries in HR-positive MBC, and prognosis improved in HER2-positive patients treated with targeted agents such as trastuzumab and lapatinib, while TNBC patients had a poorer prognosis;
④ Recurrence-free survival events (RFS) >5 years suggest a better prognosis for patients.
Visceral metastasis is an important poor prognostic factor in advanced breast cancer: in several clinical studies of MBC patients, visceral metastatic MBC accounted for the majority of cases. Patients with visceral metastases have a worse prognosis and a lower survival rate compared to patients with local metastases, soft tissue and bone metastases, with a median survival of only 0.7 years.
In Chinese patients, visceral metastases are also an important factor in prognosis, with patients who develop visceral metastases having a significantly worse prognosis than those who do not. A clinical analysis of Chinese MBC patients published in Oncology showed that the presence or absence of visceral metastases significantly affected the prognosis of MBC. Therefore, the presence of visceral metastases in MBC remains a challenge for clinical management.
Exploring treatment strategies for patients with advanced breast cancer with visceral metastases
Treatment options for MBC: Current therapies cannot completely cure MBC; therefore, the treatment goals for MBC are to prolong survival, delay disease progression, relieve clinical symptoms, and improve or maintain quality of life. The selection of treatment options for MBC should take into account tumor factors, previous treatment, patient condition, and patient’s willingness for treatment. In addition, other aspects, such as the convenience and feasibility of treatment, should be considered.
Recommendations for indications for chemotherapy in guidelines: The National Comprehensive Cancer Network (NCCN) guidelines recommend that patients with HR-negative and tumors not limited to bone or soft tissue, i.e., symptomatic visceral metastases or patients with HR-positive and resistant to endocrine therapy should receive chemotherapy; the European Society of Clinical Medical Oncology (ESMO) guidelines define indications for chemotherapy as HE-negative, HER2(++++);
HR-positive patients with failed or resistant endocrine therapy, rapid tumor progression and need for rapid control, large tumor load, symptomatic visceral metastases and visceral crisis; the guidelines and specifications of the Chinese Anti-Cancer Society for breast cancer diagnosis and treatment state that patients with HR-negative, symptomatic visceral metastases, HR-positive but resistant to endocrine therapy and those aged <35 years can be considered for chemotherapy treatment.
Choice of first-line chemotherapy regimen: A meta-analysis published in BreastCancerRes showed that patients with concomitant visceral metastases receiving combination chemotherapy increased efficiency (P<0,00001), prolonged time to disease progression [TTP, risk ratio (HR) 0,78, P<0,00001] and prolonged overall survival (OS. HR=0, 88, P<0, 001).
Patients are recommended to prefer combination chemotherapy regimens when the following factors are present: extensive metastases (e.g., visceral metastases); symptomatic and requiring rapid disease control; rapid tumor progression and good patient tolerability.
A study published in the Journal of Clinical Oncology (JClinOncol) compared the efficacy of first-line treatment with gemcitabine + paclitaxel (GT) versus single-agent paclitaxel for advanced MBC. The study included locally recurrent or metastatic breast cancer after one prior anthracycline-based adjuvant or neoadjuvant treatment, randomized to receive either the GT regimen (n=266) or single-agent paclitaxel (n=263).
The results showed that the median OS was prolonged by 2,8 months, HR=0,82, P=0,0489; median TTP was prolonged by 2,1 months, HR=0,70, P=0,0002 in the GT group compared with the single-agent paclitaxel group, in which the combination therapy significantly improved the disease remission rate by 60% in patients with visceral metastases (35,6% versus 21,9%, P=0,003).
The efficacy of the GT regimen was also explored in another clinical study in Chinese patients. The study included 60 Chinese patients with MBC, and the common metastatic sites were 51.7% for lung metastases, 28.3% for axillary lymph node metastases, 26.7% for supraclavicular lymph node metastases, and 26.7% for bone metastases. The results showed that patients treated with the GT regimen had an objective remission rate of 50%. Meanwhile, the combination regimen was well tolerated by patients with manageable grade 3 to 4 adverse reactions and low perceived adverse reactions compared with similar chemotherapeutic agents.
The KCSG-BR0702 study continued the GT regimen in patients who did not progress after 6 cycles of first-line treatment. The results showed that the median progression-free survival (PFS) period was significantly longer in the maintenance treatment group compared with the control group (7,5 months versus 3,8 months, HR=0,73, P=0,026); the 6-month PFS rate was also significantly higher (59,7% versus 36,0%, P<0,001). For the subgroup of patients with visceral metastases, GT maintenance therapy significantly reduced the risk of disease progression by 30%.
Exploring other therapeutic agents and options: As the level of treatment continues to advance, several new agents have shown advantages in the treatment of MBC. Studies have demonstrated that eribulin can prolong OS in patients and benefit the visceral metastasis subgroup. Results from clinical trials of eszopiclone alone and in combination with chemotherapy have also shown some activity in the treatment of visceral metastases. Of course, more drugs need to be explored in follow-up studies.