Local recurrence after radical mastectomy for breast cancer refers to the recurrence of the ipsilateral chest wall or (and) local lymph nodes after surgery. The recurrence rate is about 5%-30%, of which chest wall recurrence is the most common, accounting for 50%-94%. Local recurrence is a sign of other distant metastases in breast cancer and is an important factor affecting survival after breast cancer surgery[2,7]. Chest wall metastasis can occur at any time after breast cancer surgery. Among the 99 patients with isolated chest wall recurrence collected in this study, the DFS was 1-264 months, the median DFS was 36 months, and the 3-year disease-free survival rate was 44.6%, 5 years was 24.2%. According to literature reports, local recurrence is the mainstay within 2–3 years. After recurrence, 60%-80% of patients develop distant metastases, including lung, liver, and bone metastases[9]. It is of great significance to analyze the risk factors of local recurrence in breast cancer patients and take corresponding preventive measures to improve the prognosis of breast cancer patients. This article is the most comprehensive study to collect data on isolated chest wall recurrence after breast cancer surgery and secondary biopsy after recurrence.
Relevant studies have shown that the recurrence and metastasis of breast cancer after surgery are related to a variety of factors. Age, tumor size, lymph node metastasis, pathological type, hormone receptor status and her-2 expression status, postoperative staging, and postoperative treatment methods may be related to the recurrence and metastasis of breast cancer after surgery[10,11]. The histological grade is closely related to tumor invasion and metastasis, and is also positively related to visceral metastasis, the higher the grade, the higher the degree of malignancy, and the earlier the local invasion and distant metastasis. Primary tumor size and local lymph node metastasis are the two main factors affecting tumor TNM staging. Most studies have shown that the larger the tumor, the more lymph node metastasis, the higher the risk of local recurrence and distant metastasis, and the worse the prognosis. The size of the tumor indirectly reflects its biological characteristics, and lymph node metastasis is one of the most common ways of tumor metastasis. Therefore, the size of the tumor and the number of lymph node metastasis are closely related to the postoperative local recurrence of breast cancer[12,13]. The results of the univariate analysis in this study found that age, postoperative T stage, and postoperative N stage were associated with DFS, but multivariate analysis results showed that they were not independent risk factors for DFS, but tissue grade was an independent risk factor for DFS.
More and more researchers are devoted to the molecular biology research of breast cancer recurrence and metastasis, hoping to clarify the molecular mechanism of breast cancer recurrence and metastasis from the perspective of molecular biology, so as to develop drugs that can effectively inhibit breast cancer recurrence and metastasis. At present, the molecular biological markers associated with breast cancer recurrence mainly include ER, PR, Ki-67, Her-2, and so on. Studies have found that patients with hormone receptor-positive cells have a high degree of cell differentiation and a low degree of malignancy [14–16]. ER and PR positivity are one of important protective factors for the recurrence and prognosis of breast cancer patients, and the risk of recurrence and metastasis of breast cancer patients receiving endocrine therapy is significantly reduced [15]. Ki-67 is an important regulator of the cell cycle and cell proliferation. Protein antigen, the higher the Ki-67, the faster the cell proliferation, the higher the degree of malignancy, and the worse the prognosis [16]. Studies have found that the expression product of the oncogene Her-2 is a key factor regulating tumor growth and plays an important role in the occurrence, development, metastasis, and prognosis of breast cancer [15]. Faneyte et al. found that the 5-year survival rate of patients with overexpression of her-2 was significantly lower than that of patients with negative expression of her-2[17]. In addition, patients with overexpression of her-2 were not sensitive to conventional adjuvant therapy and were more likely to develop local lymph node metastasis, which would develop a poor prognosis. The results of multivariate analysis in this study showed that positive hormone receptor expression, ki-67 ≥ 14, and her-2 positive were independent risk factors for chest wall recurrence.
In recent years, breast cancer tends to be younger. Young patients have stronger tumor invasiveness, faster disease progression, and earlier local recurrence and distant metastasis. Some studies believe that younger age is an independent risk factor for breast cancer recurrence and metastasis after surgery. Reports on the relationship between local recurrence of cancer are inconsistent[18–21]. This study divided age into ≥ 50-year-old group and < 50-year-old group. Univariate analysis showed that the DFS of different age groups was statistically different, but multivariate analysis showed that age was not an independent risk factor for chest wall recurrence.
The main methods of breast cancer treatment include surgery, chemotherapy, radiotherapy, targeted therapy, endocrine therapy, etc. Studies have found that reasonable and effective adjuvant therapy after radical mastectomy can significantly improve the 5-year survival rate of patients. In terms of postoperative adjuvant chemotherapy, adjuvant chemotherapy after breast cancer surgery can significantly prolong the DFS of local recurrence, especially for hormone receptor-negative patient[22,23]. Another study confirmed that postoperative adjuvant endocrine therapy can significantly reduce the rate of local recurrence and distant metastasis[24]. Regarding the sequence of postoperative adjuvant chemotherapy and endocrine therapy, it is recommended to complete adjuvant chemotherapy before starting endocrine therapy[22,23]. In terms of local radiotherapy, many studies have confirmed that it has a significant effect on controlling the local recurrence rate after breast cancer surgery and improving long-term survival[24,25], and it is one of the main methods for postoperative local treatment of breast cancer, especially for patients with ≥ 4 positive axillary lymph nodes[9,26,27]. The univariate analysis results of this study showed that the comprehensive treatment mode of postoperative adjuvant chemotherapy, endocrine therapy, and radiotherapy can significantly prolong the DFS of chest wall metastasis after breast cancer surgery. Further COX multivariate analysis showed that adjuvant chemotherapy was an independent protective factor for chest wall metastasis after breast cancer surgery. Targeted therapy was not included in this study's univariate and multivariate analysis because there were only 9 patients who received targeted therapy in the collected patients, and the number of cases was unbalanced with an obvious bias.
This study had several limitations. Firstly, the clinical and molecular factors were assessed retrospectively from medical records, which may have introduced errors or missing data. Additionally, the study did not perform a rigorous assessment of inter-rater reliability to ensure consistency in data collection and interpretation. Lastly, the study only analyzed DFS as the primary outcome, and did not assess other clinically relevant outcomes, such as overall survival or quality of life. Therefore, the study may not provide a comprehensive understanding of the impact of chest wall metastasis on breast cancer patients. while this study provides valuable insights into the clinical and molecular factors associated with chest wall metastasis in breast cancer patients, the results should be interpreted with caution due to the limitations discussed above. Further studies with larger sample sizes, more diverse patient populations, and longer follow-up periods are needed to validate these findings and provide a more comprehensive understanding of the impact of chest wall metastasis on breast cancer patients.
In conclusion, this study showed that surgical grade, postoperative ER, PR, Ki-67, HER-2 expression, and postoperative adjuvant chemotherapy were independent risk factors affecting the local recurrence of breast cancer after surgery. As local recurrence after breast cancer surgery increases the risk of distant metastasis, therefore, identifying the risk factors of recurrence and selecting individualized comprehensive treatment for patients is crucial to reduce the risk of postoperative local recurrence, improve prognosis, and enhance survival.