Some breast cancer patients may have microscopic subclinical metastases in their bodies after surgery, and some of them will have recurrence or metastasis. Using some relevant factors as prognostic indicators to distinguish the cases prone to recurrence or metastasis, and giving systemic adjuvant treatment will effectively improve the therapeutic efficacy. There are various factors known to affect prognosis, mainly divided into two categories: clinicopathological factors and biological factors.
I. Clinicopathological predictors
Among the clinicopathological predictors of breast cancer, the most recognized factors that have a prognostic effect on breast cancer include lymph node metastasis, tumor size, degree of differentiation and histological type, etc.
The prognosis of carcinoma in situ without infiltration (including intraductal carcinoma, lobular carcinoma in situ and papillary Paget’s disease) is the best and almost completely curable. Once infiltration occurs, the prognosis becomes worse, and the more extensive the infiltration is, the worse the prognosis will be.
The histological type of breast cancer is one of the important factors affecting the prognosis. Non-invasive carcinoma has the best prognosis, early infiltrating carcinoma is the second best, infiltrating specific carcinoma is okay, and infiltrating non-specific carcinoma is poor. The 10-year survival rate of patients with tubular carcinoma, medullary carcinoma with massive lymphocytic infiltration, mucinous carcinoma and papillary carcinoma is higher, while the prognosis of invasive lobular carcinoma and hard carcinoma is the worst.
3. Histological grading A large number of studies have shown that the histological grading of breast cancer is closely related to the prognosis. Tumors with histological grade 1 have good differentiation and better prognosis; tumors with histological grade 3 have poor differentiation and poor prognosis.
4.Tumors with peri-cancerous boundary mainly grow swollen and have good prognosis if they are clearly demarcated from surrounding tissues or have pseudo-envelope; on the contrary, they have poor prognosis.
5.Lymphocyte infiltration around the tumor or in the interstitium has a better prognosis. The more lymphocytes infiltrated, the better the prognosis, which indicates the strong immune response function of the body; otherwise, the prognosis is poor.
Lymph node involvement Over the years, studies have shown that lymph node metastasis is one of the decisive factors affecting the prognosis of breast cancer. The prognosis is good if there is no lymph node metastasis, but poor if there is metastasis. The higher the number of metastatic lymph nodes, the worse the prognosis.
The prognosis is poor if there are cancer cell emboli in the interstitial tumor or adjacent blood vessels or lymphatic vessels.
8.Most of the data at home and abroad show that the prognosis of lymph node tissue cell proliferation is better; otherwise, the prognosis is poor.
Biological factors predictive index
In recent years, the value of biological factors in breast cancer prognosis and efficacy prediction has attracted wide attention. Biological factors can well reflect the biological characteristics of breast cancer, which are related to the etiology and development of tumor, and are of great significance to the prognosis of breast cancer. The ideal biological prognostic indicators should have the following conditions: ①These factors can explain some biological phenomena, which are related to the development or metastasis of the tumor. (2) They have prognostic value, independent of known pathological indicators, and can be used as a basis for selecting adjuvant therapy. ③Can be used in prospective studies for the selection of treatment regimens to improve efficacy. ④It is easy to operate and reproducible, and can be promoted in general laboratories. There are several types of indicators commonly used to predict prognosis, among which hormone receptor and HER2 gene expression have very important values in determining breast cancer prognosis.
Steroid hormone receptors estrogen receptor (ER) and progesterone receptor (PR) can regulate the growth and differentiation of breast cells under normal conditions, and have an important role in prognosis determination in breast cancer. Numerous studies have shown that the prognosis of ER-positive and PR-positive breast cancers is better than that of negative ones. The prognostic value of PR in lymph node-negative breast cancer is uncertain, but most of the literature suggests that the prognosis of PR-positive patients is better. ER and PR expression are related to the proliferative ability of breast cancer, but not to breast cancer metastasis. Also, the expression of ER and PR can guide the choice of endocrine therapy for breast cancer. However, it has been reported that ER will lose its value as a prognostic indicator in long-term follow-up, thus it is unclear whether hormone receptors are permanent prognostic indicators for breast cancer.
2. Growth factors and their receptors include epidermal growth factor (EGF), HER-2 (c-erbB-2), H-ras, insulinlikegrowthfactor and retinoid receptor. High expression of various growth factors and their receptors can be found in most breast cancers, which is often the result of mutations in the corresponding oncogenes in the tumor. Her-2 gene is one of the most studied breast cancer oncogenes, and its high expression is closely related to the poor prognosis of breast cancer, such as hormone receptor negative and axillary lymph node positive, and is also associated with breast cancer drug resistance mechanism. A large number of studies have concluded that breast cancer with high Her-2 expression has a poor prognosis. The prognosis of breast cancer with high expression of epidermal growth factor and insulin-like growth factor has also been reported.
3. Tumor proliferation rate indicators such as thymidine labeling index (TLl), Ki-67 antigen, PCNA, etc. The proliferation status of tumor cells reflects the ability of cell mitosis. When tumor cells proliferate rapidly, their mitotic capacity is high, and their prognosis is poor; when tumor cells proliferate slowly, their mitotic capacity is low, and their prognosis is better. Numerous studies have found that TIL is a very useful prognostic indicator for breast cancer, and is an independent prognostic indicator for both DFS and OS of breast cancer. TII was classified as low, medium and high, and the difference in DFS between low and high could reach 30%.
4.The relative DNA content of tumor cells, DNA ploidy, DNA index and S-phase cell percentage are measured in tumor tissues can indicate the growth rate of tumor and cell differentiation, which can be more helpful to the prognosis of breast cancer, and also reflect the tumor biological behavior of breast cancer. DNA ploidy is widely used in the assessment of breast cancer prognosis, and it is usually detected using static cell analyzer or It is usually detected by static cell analyzer or flow cytometry. The prevalence of various types of alloploid DNA in breast cancer has been reported in the literature to be 44-92%, and the results of DNA content assays usually correlate with the clinicopathological characteristics of breast cancer. Tumors with predominantly diploid DNA tend to be less malignant and more positive for ER and PR; tumors with predominantly heteroploid DNA tend to show higher grade and negative for hormone receptors. Pathological types with good prognosis, such as adenoid carcinoma, mucinous adenocarcinoma and papillary carcinoma tend to be diploid. DNA ploidy has also been found to correlate with tumor staging (size, lymph node status), with heteroploidy more often seen in tumors with large size and high rates of lymph node metastasis. Studies have shown that DNA ploidy alone is not yet a strong prognostic indicator for breast cancer, whereas when combined with the proportion of S-stage cells as an assessment indicator there is a strong relationship between recurrence and survival in patients with positive and negative axillary lymph nodes. The value of DNA ploidy and S-stage cell count ratio as prognostic factors in breast cancer is not yet fully confirmed due to the different testing standards used by different laboratories.
5. Indicators of local tumor invasion such as histone D (cathepsin-D), fibrinogen activator (plasmino genactivator), laminin receptor, etc. Proteases such as histone D are often secreted in cancer cells and can promote tumor infiltration by degrading cell basement membrane and intercellular matrix under acidic environment, which is one of the important links in tumor metastasis. Some studies have found that breast cancers with high cathepsin-D levels have poor prognosis, both in lymph node positive or negative patients, and are also independent prognostic indicators of breast cancer. The expression of other proteases in breast cancer has also been reported to have an impact on the prognosis of breast cancer, and it is believed that the higher the expression of the indicators of local invasion, the worse the prognosis.
6. Tumor growth inhibitory and anti-metastatic genes such as nm23, p53, wAFl/cIPl, etc. It is now generally accepted that tumor growth is influenced by the balance between oncogenes and oncogenes, and mutation and inactivation of oncogenes will promote cell growth and contribute to malignant transformation of cells, thus breast cancer with inactivated oncogenes has a poorer prognosis. The most studied oncogene in breast cancer is p53, which is located on the long arm of chromosome 17. The wild-type p53 gene is a tumor suppressor gene that inhibits malignant transformation and controls cell growth, and is a negative regulator of cell growth, while the mutant p53 protein promotes malignant transformation. Immunogenic breast cancer with p53 accounts for 40% to 50%. p53 overexpression is associated with poor tumor differentiation and ER(I) in breast cancer, and is less related to lymph node metastasis, but breast cancer with positive lymph nodes and simultaneous p53 positivity has a poor prognosis. There are conflicting views regarding the relationship between p53 detection and clinical prognosis. Some authors believe that lymph node-negative patients with mutant p53 detection have a shorter survival. However, other authors deny that there is a correlation between them. There are also reports suggesting that p53 detection is associated with better responsiveness to chemotherapy. nm23 gene is a gene that inhibits tumor metastasis, and in breast cancer, the level of nm23 gene transcription is directly related to the degree of tumor differentiation and axillary lymph node metastasis. breast cancers with high nm23 transcript levels have higher differentiation, lower lymph node metastasis rate and longer postoperative survival, while those with low nm23 transcript levels have On the contrary.
7. Tumor vascular growth factors such as factor VIII and cD31 index and the number of tumor neovascularization. There are many studies confirming that the ability of inducing neovascularization in the process of transformation of normal cells to malignant gradually increases. In breast cancer, the number of neovascularization is not only related to the blood supply of proliferating cancer cells in breast cancer, but also represents the invasion and metastatic ability of cancer cells. It was found that 100% of breast cancer specimens with microvessel counts exceeding 100/200 times the field of view will have distant metastasis. It was also found that the microvessel count was significantly higher in lymph node positive breast cancers than in lymph node nonmetastatic breast cancers. The multifactorial analysis concluded that microvessel count is an independent prognostic indicator for breast cancer.
8, hepatogloblin-relatedprotein, heatshockprotein, pS2 and apoptotic index.
From the above various clinical and laboratory prognostic indicators of breast cancer, lymph node metastasis and tumor size are recognized as indicators with great value in determining the prognosis of breast cancer. However, some breast cancers with negative lymph nodes and small tumor size may also develop early distant metastasis, thus relying on one or a few prognostic indicators alone will not be able to make a good prognostic judgment for each specific breast cancer case. From the development of breast cancer research, the biological prognostic factors of breast cancer will play an increasingly important role in determining the prognosis of breast cancer, because the biological prognostic factors of breast cancer can not only provide prognostic judgment, but also each biological factor represents a certain biological characteristic of the tumor, and through the study of its biological prognostic factors, it will be possible to classify various breast cancers with the same pathological type and tumor stage into various prognostic factors according to their biological characteristics. The study of biological prognostic factors will make it possible to classify breast cancers with the same pathological type and tumor stage into various prognostic subtypes according to their biological characteristics, which can make a more accurate prognostic judgment of breast cancer and help guide the individualized treatment of breast cancer.