I. What is breast cancer? What are its risk factors?
Breast cancer is a malignant tumor originating from the breast tissue.
Each breast has 15-20 lobes, and each lobe is composed of many glandular lobules, which in turn are composed of milk-secreting glandular vesicles. The lobes, lobules and follicles are connected by ducts.
Each mammary gland has blood vessels and lymphatic vessels. The lymphatic ducts carry almost colorless lymph fluid and are connected to lymph nodes, which are tissues like soybeans distributed throughout the body. The lymph nodes are located in the armpits, supraclavicular region and on the sides of the back of the sternum. The most common type of breast cancer is ductal carcinoma, which originates from ductal cells. Lobular carcinoma, which originates from the lobes and lobules, often occurs in both breasts. Inflammatory breast cancer is an uncommon type that presents with redness, heat and swelling.
2.Risk factors for developing breast cancer
Any factor that increases the chance of developing the disease is called a risk factor. Risk factors for breast cancer include: advanced age, early menarche, advanced first birth or never had children, history of breast cancer or history of benign breast cancer, mother or sister with breast cancer, history of radiation therapy to the chest or breast, high dose x-ray exposure to the breast, oral estrogen and alcohol abuse, etc. Caucasians are more likely to develop the disease than other races.
Genes within cells are carriers of genetic information from parents. Familial or hereditary breast cancer accounts for 5-10% of all breast cancers, and mutations associated with breast cancer are more common in certain ethnic groups. Patients with breast cancer who have altered breast cancer-related genes have an increased chance of developing cancer in the opposite breast and, in addition, have an increased risk of developing ovarian and other cancers. Men who have altered breast cancer-related genes also have an increased risk of developing breast cancer. In families with a high incidence of breast cancer, the risk of developing cancer can be predicted by testing for mutations in certain genes.
Screening methods and diagnosis of breast cancer
1. Physical examination can mostly detect breast lumps, and the following tests help to complete the diagnosis of breast cancer.
Mammogram: a kind of x-ray of the breast
Biopsy: Removal of part of the breast tissue or needle aspiration of the cells of the mass, and the pathologist will observe whether there are cancer cells under the microscope. After a breast lump is found, the doctor can perform four forms of biopsy: complete excision of the entire lump tissue biopsy, partial excision biopsy, coarse needle aspiration biopsy with core, and fine needle aspiration biopsy.
Estrogen and progesterone receptor test: It is a test to detect the number of estrogen receptors and progesterone receptors on cancer cells. If breast cancer is diagnosed, it should be further tested whether the tumor growth depends on estrogen and progesterone. Based on the test results, a decision will be made whether to apply endocrine therapy to stop the growth of the tumor.
Magnetic resonance imaging (MRI): It is an imaging method to obtain structural changes in various parts of the body through the application of magnetic field, radiation waves and computer.
2. Factors affecting prognosis (chance of cure) and choice of treatment.
Stage of the tumor (tumor size, metastatic lymph nodes or distant metastasis)
Type of breast cancer
Levels of estrogen receptor and progesterone receptor in cancer cells
Whether human epidermal growth factor receptor number two (Her-2/neu) is at high levels
How fast or slow the tumor grows
Age, health status, menopause or not
Newly diagnosed breast cancer or recurrence after treatment
3.Staging of breast cancer
After the diagnosis of breast cancer is confirmed, there are some tests to determine whether the tumor is confined to the breast or has spread to distant parts of the body. Staging determines the choice of treatment and the effectiveness of treatment, so it is very important. The staging of breast cancer is as follows.
Stage 0 (carcinoma in situ): There are two types of carcinoma in situ as follows
Ductal carcinoma in situ: The abnormal cells are confined within the ducts without invading outward. If they break through the ducts and invade the surrounding tissues, they become invasive carcinoma. It is not possible to predict which tumors will develop into invasive carcinoma.
Lobular carcinoma in situ: The abnormal cells are confined to the lobules of the breast and rarely develop into invasive carcinoma. However, patients with lobular carcinoma in situ have an increased risk of developing contralateral breast cancer.
Stage I: Tumor diameter <2 cm and no extramammary metastasis
Stage II.
Stage IIA: no breast lump found, but axillary lymph node metastasis; or lump diameter ≤2cm with axillary lymph node metastasis; or lump 2-5cm, but no axillary lymph node metastasis
Stage IIB: mass diameter 2-5cm, axillary lymph node metastasis; or diameter >5cm, but no axillary lymph node metastasis
Stage III
Stage IIIA: Regardless of the size of the tumor or whether a breast lump is found, axillary lymph node metastasis occurred and fused with each other, or fixed with other tissues, or lymph node metastasis occurred near the posterior sternum
Stage IIIB: Tumor of any size that has invaded the chest wall or breast skin and has metastasized and fused with each other in the axillary lymph nodes, or fixed with other tissues, or metastasized in the lymph nodes near the posterior sternum.
Stage IIIC: Regardless of the size of the tumor or whether the tumor is found in the breast, as long as the tumor is found to have invaded the chest wall and/or breast skin and metastasized to the supraclavicular or subclavicular lymph nodes, or metastasized to the internal breast lymph nodes near the axilla and sternum. Stage IIIC is further divided into operable and inoperable IIIC
Operable IIIC: (1) 10 or more axillary lymph node metastases; (2) subclavian lymph node metastases; (3) lymph node metastases in the axilla and near the sternum
Inoperable IIIC: supraclavicular lymph node metastasis
Stage IV: distant metastases, mostly bone, lung, liver and brain metastases.
Inflammatory breast cancer: breast cancer with extensive metastasis of tumor to breast skin is called inflammatory breast cancer, which manifests as redness, swelling and heat. The redness and heat are caused by the tumor cells blocking the skin lymphatic vessels, and the skin of the breast may also show orange peel-like changes. Inflammatory breast cancer may have no breast lumps. Inflammatory breast cancer can be stage IIIB, stage IIIC, or already stage IV
Recurrent breast cancer: It refers to recurrence after treatment and can be found mostly in the chest wall or other parts of the breast.
Treatment of breast cancer
Breast cancer treatment should be individualized. There are some methods that belong to the standard approach (currently commonly used treatment methods) and some methods that are under clinical trials. When clinical trials show that the new treatment is better than the standard treatment, this treatment may become the new standard treatment.
Four standard treatments.
1. Surgery.
In most patients, the tumor can be completely removed surgically, usually by removing the lymph nodes in the axilla and sending them to the pathology department for examination, where the pathologist can observe whether there is cancer infiltration under the microscope.
(1) Breast-conserving surgery
Breast-conserving surgery is a surgical procedure that only removes the tumor while preserving the breast. During or after the breast-conserving surgery, another biopsy is done to remove part of the axillary lymph nodes to find out whether there is metastasis. The procedure includes
Mass excision: removal of the mass and a small amount of surrounding normal tissue.
Partial mastectomy: removal of part of the breast where the mass is located and a small amount of surrounding normal tissue
(2) Other surgical procedures.
Total mastectomy: total removal of the affected breast, also called a separate mastectomy, with an additional incision made during or after surgery to remove part of the axillary lymph node biopsy.
Modified radical surgery: Surgery to remove all of the affected side of the breast, most of the axillary lymph nodes and the muscle under the breast, and sometimes some of the chest wall muscle.
Radical surgery: Surgery to remove the affected breast, the chest wall muscle underneath the breast, and all of the axillary lymph nodes. This type of surgery is also called Halsted radical surgery.
Even though the surgeon removes all of the cancerous tissue visible during surgery, some patients require postoperative radiation, chemotherapy or endocrine therapy to kill any remaining cancer cells after surgery, with the goal of increasing the cure rate. This post-operative treatment is called adjuvant therapy.
If a patient is going to have a mastectomy, breast reconstruction may be considered. It can be done intraoperatively or postoperatively. Breast reconstruction can be done by augmenting the breast with the patient’s own tissue (not breast), or by placing a special bag filled with saline to make a prosthetic breast, or by filling it with silicone.
2.Radiotherapy
Radiation therapy is an anti-tumor method that uses high-energy X-rays or other radiation to kill tumor cells or stop their growth. The former is to irradiate the tumor from outside the body with the radiation emitted by large machines, while the internal radiation is to irradiate the tumor by putting the radioactive material enclosed in fine needles, particles, metal wires or catheters directly into or around the tumor. The route of radiotherapy depends on the tumor staging and staging.
3.Chemotherapy
Chemotherapy, short for chemotherapy, is an anti-tumor treatment that kills tumor cells directly or prevents them from dividing and proliferating. Chemotherapy drugs can be administered orally, intravenously or intramuscularly into the bloodstream and act on tumor cells throughout the body, which is called systemic chemotherapy or systemic chemotherapy. Chemotherapeutic drugs can also be injected directly into the spinal canal, organs or body cavity (e.g. abdominal cavity) to control the tumor in the local area, which is called local chemotherapy. The route of chemotherapy depends on the tumor staging and staging.
4.Hormone therapy
Hormone therapy, also called endocrine therapy, is a method that can stop the growth of cancer cells by inhibiting or blocking the activity of hormones. Some hormones promote the growth of cancer. If the examination proves that cancer cells have receptor binding, drugs, surgery and radiotherapy can reduce the production of hormones or block the effect of hormones. The growth of hormone-dependent breast cancer needs to be stimulated by estrogen in the body in order to grow. In premenopausal women, estrogen is mainly synthesized by the ovaries and secreted into the bloodstream. Treatment to block the production of estrogen by the ovaries is called ovarian depot. After menopause, estrogen is mainly synthesized in the body by fat and muscle tissues under the action of aromatase enzymes. Aromatase inhibitors are used in postmenopausal hormone-dependent breast cancer. Aromatase inhibitors reduce estrogen by blocking the conversion of androgens to estrogen.
Triamcinolone blocks the action of estrogen and is used in pre- or postmenopausal patients with early-stage and metastatic breast cancer. However, triamcinolone or estrogen therapy slightly increases the risk of endometrial cancer, and those taking oral triamcinolone should have annual gynecologic examinations and report any vaginal bleeding outside of menstrual periods to their physician early.
Aromatase inhibitors may be substituted for triamcinolone for postmenopausal breast cancer or switched to aromatase inhibitors after 2 or more years of oral triamcinolone. Clinical studies comparing the efficacy of aromatase inhibitors and triamcinolone acetonide in the treatment of metastatic breast cancer have not yet been completed.
New advances in the diagnosis and treatment of breast cancer
1.Sentinel lymph node biopsy
The sentinel lymph node is the first lymph node from which the tumor cells shed from the tumor body are drained through lymphatic vessels and is most vulnerable to tumor infiltration. Sentinel lymph node biopsy followed by surgery has become a new fashion in breast cancer treatment. Sentinel lymph node biopsy is performed during surgery, and injection of melanoma or radioactive substance around the tumor will flow along the lymphatic vessels to the lymph nodes, remove the first stained lymph nodes and detect cancer cells under the microscope, if no cancer metastasis is found, there is no need to remove more lymph nodes. After the biopsy of the anterior lymph nodes is completed, the surgeon then removes the tumor (breast-conserving surgery or mastectomy).
2. High-dose chemotherapy and stem cell transplantation.
High-dose chemotherapy can cause severe bone marrow suppression or even death. Transfusion of hematopoietic stem cells after chemotherapy can help restore bone marrow hematopoietic function. Hematopoietic stem cells taken from the patient’s own or another person’s blood or bone marrow are stored frozen and thawed and revived before use. Studies have shown that high-dose chemotherapy for breast cancer is not superior to standard chemotherapy, and this method is currently only used in clinical trials.
3.Adjuvant therapy with monoclonal antibodies
About a quarter of breast cancer patients have cancer cells that are enriched with a molecule that transmits growth signals —- growth factor protein Her-2 on the surface, and if we can block the function of the Her-2 molecule we can inhibit the proliferation of the tumor. We can use immune cells to produce specific antibodies against a certain molecule, which can specifically recognize the corresponding molecule in the body and kill cancer cells that express it. Each immune cell secretes one antibody, and if an antibody-secreting cell is expanded in large numbers in the laboratory, the resulting antibody is called a monoclonal antibody, or monoclonal antibody for short. The current monoclonal antibodies against Her-2 are trastuzumab (trade name Herceptin), which has good efficacy in combination with chemotherapy for advanced breast cancer, and trastuzumab combined with chemotherapy for breast cancer patients with high Her-2 expression can reduce tumor recurrence after surgery.
4.Tyrosine kinase inhibitors
Her-2 molecule, whose full Chinese name is “human epidermal growth factor receptor number two”, can be divided into extracellular region, transmembrane region and intracellular region, and when the growth factor binds to Her-2, it promotes tumor growth by activating tyrosine kinase in the intracellular region. The tyrosine kinase inhibitors currently used for breast cancer treatment include lapatinib, which is mainly used for Her-2-positive breast cancer that has failed via Herceptin. The value of lapatinib in postoperative adjuvant therapy is currently being investigated.