How to treat breast cancer

Breast cancer is the most common tumor among women. In recent years, the incidence of breast cancer has increased steadily, but the mortality rate has decreased, which is attributed to the early diagnosis of breast cancer and the improvement of surgical techniques and radiotherapy and chemotherapy.

In addition, the new targeted drug therapy has also significantly improved the survival rate of breast cancer patients. Despite great progress in diagnosis and treatment technology, breast cancer is still the second leading cause of cancer death in women. This paper summarizes the latest progress in the treatment of breast cancer, and mainly discusses how to carry out individualized treatment according to the tumor biological characteristics and molecular subtypes of patients in the era of targeted treatment of breast cancer.

Early breast cancer

1, diagnosis

Diagnostic guidelines for early breast cancer have not changed much so far. British national health insurance system

Breast screening

The plan suggests that people between the ages of 47 and 73 should have regular mammograms. Both men and women should go to the local breast specialist as soon as possible (usually two weeks) to avoid delaying treatment. X-ray, B-ultrasound and biopsy of breast should be improved as needed.

2. Local treatment

Surgical treatment must be completely removed. The survival time of patients was basically the same after breast-conserving surgery, radiotherapy and total mastectomy. For the surgical treatment of breast cancer, the resection range should be at least 65438±0mm from the tumor edge, and it should have a good cosmetic effect. Breast cancer resection is recommended in the following situations: breast-conserving surgery is not suitable for tumor size, breast multifocal lesions and large masses, even breast-conserving surgery can not achieve good cosmetic effect and patient requirements. Preoperative adjuvant therapy to reduce tumor volume is increasingly recommended, which can increase the chances of breast-conserving surgery.

3, axillary lymph node dissection

At the same time of diagnosing breast cancer, ultrasound examination or suspicious lymph node biopsy should be performed on the ipsilateral axillary lymph nodes to determine the stage of breast cancer. If axillary lymph nodes are negative, sentinel lymph node biopsy (SLNB) is feasible, usually at the same time as breast surgery. In the past, sentinel lymph node positive patients should undergo total axillary lymph node dissection (ALND). The main purpose of ALND is to reduce axillary recurrence. In fact, 50% of sentinel lymph node positive patients did not find any other axillary lymph node invasion after ALND. Should sentinel lymph node positive patients receive further ALND treatment? The clinical study of Z00 1 1 answered this question.

This study is a phase 3 randomized controlled study involving more than 800 breast cancer patients. 89 1 patients were randomly divided into SLNB group (446 cases) or further ALND group (445 cases). All patients received segmental mastectomy and breast radiotherapy, and received systemic adjuvant therapy according to their condition. After a median follow-up of 6.3 years, the 5-year recurrence rates of breast cancer in ALND group and SLNB group were 3.7% and 2.65438 0% respectively.

The 5-year recurrence rates of lymph nodes were 0.6% and 65438 0.3% respectively.

From the results of Z00 1 1 test, it can be seen that there is no significant difference in overall survival, disease-free survival and local recurrence rate between breast cancer patients with positive sentinel lymph node metastasis and breast cancer patients without axillary lymph node dissection, that is, breast cancer patients with positive sentinel lymph node cannot benefit from further axillary lymph node dissection in these aspects.

There is no unified conclusion as to whether patients with sentinel lymph node positive in breast cancer should be further treated with ALND. Recent guidelines suggest that if 1 or 2 sentinel lymph nodes are positive, patients undergoing breast-conserving surgery after radiotherapy may not need further ALND.

4. Adjuvant treatment according to the pathology and molecular subtypes of breast cancer.

The molecular typing of estrogen receptor positive patients with poor traditional staging is heterogeneous, and their sensitivity to chemotherapy and responsiveness to endocrine therapy are also different. The prognosis of poor staging caused by high T stage and positive lymph nodes may be affected by some good molecular biological characteristics, such as positive hormone receptor, low expression of Ki-67 and low risk of 2 1 gene.

When the staging and typing are inconsistent, single-gene and multi-gene spectral detection may bring us more information, but at present, the advantages of multi-gene detection are mainly reflected in the prediction of prognosis, and the prediction of treatment effect needs further confirmation.

For patients with poor pathological stages, standard chemotherapy should be avoided if the hormone reactivity is good, Her2 is negative and the proliferation is low (2 1 gene or 70 gene expression is low risk). The most important thing is to distinguish which patients are estrogen receptor positive and which are negative, because the treatment and prognosis of these two types of patients are completely different.

Adjuvant chemotherapy for early breast cancer

1, the first 5 years of hormone therapy

The purpose of adjuvant therapy is to improve the cure chance by eliminating micrometastasis. About 80% of breast cancer patients are positive for estrogen receptor. For these patients, adjuvant tamoxifen treatment for five years can reduce the recurrence rate by 465,438+0% and the mortality rate by 365,438+0%. Tamoxifen is still the standard treatment for premenopausal breast cancer patients.

For postmenopausal breast cancer patients, studies have proved that aromatase inhibitors are superior to tamoxifen. Data from two large studies, ATAC and BIG 1-98, show that anastrozole and letrozole are superior to tamoxifen.

It is important to monitor the bone mineral density of patients treated with aromatase inhibitors. In case of osteoporosis, calcium and vitamin D should be supplemented, and bisphosphate and Prolia(denosumab) can be added if necessary. For breast cancer patients diagnosed before menopause, it is still beneficial to use aromatase inhibitors (physiology or chemotherapy) after menopause.

2.5 years later, hormone adjuvant therapy.

Most patients with estrogen receptor-positive breast cancer relapse after 5 years. For postmenopausal patients who have been treated with tamoxifen for 5 years, the relative risk can be reduced by 42% if letrozole, a non-aromatase inhibitor, is used. For patients who have been treated with tamoxifen for 5 years and are not menopausal, or who cannot tolerate aromatase inhibitors, continuing to use tamoxifen can benefit patients.

The international atlas (comparing long-term and short-term adjuvant tamoxifen therapy) shows that taking tamoxifen 10 year can reduce the late recurrence rate and mortality rate of ER+ breast cancer patients, and the effect is good. The main additional benefit of continuing to take tamoxifen is to reduce the mortality rate in the second decade after breast cancer diagnosis.

ATTom's research also reached the same result. Combining the results of ATLAS study and ATTom study, for breast cancer with estrogen receptor positive, extending tamoxifen adjuvant therapy to 10 years instead of 5 years can further reduce the risk of recurrence. Compared with not using tamoxifen, using tamoxifen as adjuvant therapy 10 year can reduce the risk of death by at least one third.

3. Chemotherapy

Chemotherapy can reduce the relative risk of breast cancer death by one third, but chemotherapy can not improve the survival time of patients, because many patients can only be cured by surgery and hormone therapy. What kind of patients need chemotherapy needs further study. We know that through molecular testing, such as

Oncotype DX can predict the prognosis of patients. In fact, this detection technology can also identify which patients can be cured by surgery and hormone therapy.

MINDACT study evaluated the clinical value of increasing gene expression profile on the basis of routine clinical and pathological examination to guide the adjuvant treatment choice of breast cancer patients. It is designed to make more patients avoid adjuvant chemotherapy and get a better quality of life.

This study is the first attempt to use gene-guided patient classification to reduce the cost of tumor treatment, which not only embodies the idea of giving appropriate treatment to suitable patients, but also emphasizes that unnecessary treatment should not be given to unsuitable patients.

Of course, in the future, we need to identify high-risk patients, so that they can get better and more adequate treatment, and further explore how to integrate better tumor subgroup classification and biomarkers for predicting curative effect into the adjuvant treatment of breast cancer. Even if breast cancer patients need chemotherapy, the formulation of chemotherapy plan is very knowledgeable. How to make a chemotherapy plan and reduce the mortality and side effects caused by chemotherapy is a problem that needs to be considered at present.

4.HER2 targeted therapy

The treatment of breast cancer has entered the era of molecular typing, and human epidermal growth factor receptor 2(HER2) positive breast cancer accounts for about 20%-30% of all breast cancer patients. HER2 is a clear prognostic indicator of breast cancer.

As the first humanized monoclonal antibody against HER2, the advent of trastuzumab changed the prognosis of patients with HER2 positive breast cancer. All clinical studies on postoperative adjuvant treatment of breast cancer suggest that surgery plus anti-HER2 drug trastuzumab can improve the DFS rate of patients, and most clinical trials also show that OS rate is improved.

For patients with large masses who are not suitable for breast-conserving surgery, preoperative adjuvant chemotherapy, HER2 targeted therapy or hormone therapy can reduce the tumor load and create conditions for breast-conserving surgery. For those breast cancer patients with complete pathological remission, especially those with negative estrogen receptor, the prognosis is better.

Patients with locally advanced breast cancer should receive adjuvant chemotherapy before radical mastectomy. For patients with inflammatory breast cancer with erythema and edema, the best treatment is preoperative adjuvant chemotherapy, and then choose surgery or radiotherapy according to the situation. Because such patients are unlikely to be positive for hormone receptors, they are more likely to be positive for HER2 gene.

Treatment of advanced breast cancer

The main purpose of selective chemotherapy for advanced breast cancer is to relieve the symptoms of patients, control the progress of the disease and improve the survival time. In the choice of chemotherapy scheme, we should also pay attention to the side effects caused by chemotherapy and minimize the toxicity of treatment. According to different subtypes, the median survival time of breast cancer after distant metastasis is different, generally ranging from half a year to 2.2 years. In the past 30 years, the overall survival time of breast cancer patients has been significantly improved, especially the breast cancer with HER2 gene positive. Metastatic breast cancer is still incurable, but the survival time and quality of life of patients can be improved through treatment.

1, hormone therapy

Hormone therapy is still the first choice for metastatic breast cancer with estrogen receptor positive. The choice of hormone therapy should be based on the patient's previous response to treatment and whether she is menopausal or not. Drug resistance is common and inevitable in hormone therapy for metastatic breast cancer. How to avoid drug resistance is the focus of current research. MTOR-mediated signaling pathway is activated at high frequency in breast cancer, which leads to hormone resistance and becomes an important target for breast cancer treatment.

A study shows that the mTOR inhibitor everolimus combined with exemestane can prolong the disease-free progression of patients with advanced breast cancer, and the risk of cancer deterioration is significantly reduced by 57% compared with exemestane alone.

Everolimus can cause serious side effects, including stomatitis, rash, diarrhea and fatigue, and pneumonia is also very common. Attention should be paid to the occurrence of these side effects during the treatment, and once they appear, they should be treated as soon as possible. Everolimus has been approved in North America and Europe for the treatment of hormone receptor-positive and HER2-positive breast cancer patients.

2. Chemotherapy

Chemotherapy is usually used for the following types of breast cancer: hormone resistant breast cancer, hormone receptor negative breast cancer, rapidly progressive breast cancer and most HER2 positive breast cancer. The choice of chemotherapy should be based on the patient's physical condition, the nature of the tumor (such as triple negative breast cancer, HER2 positive) and the previous response to chemotherapy. Chemotherapy is generally a short course of treatment, which is completed in several cycles. As for how many courses of chemotherapy are needed, there is no unified conclusion at present.

3.HER2 targeted therapy

Before the advent of targeted drugs, HER2 positive breast cancer patients were considered to have a poor prognosis. With the appearance of humanized monoclonal antibody against HER2, the prognosis of such patients has been significantly improved. Tratuzumab combined with Taxus chinensis in

HER2

In neoadjuvant therapy, the survival time of patients with positive breast cancer is significantly improved. Rapatinib is a small molecule kinase inhibitor, which can be used for breast cancer patients who are HER2 positive but have not received trastuzumab treatment. At present, rapatinib has been approved in combination with capecitabine as a second-line drug for the treatment of HER2-positive breast cancer.

Tratuzumab EMTANSINE (T-DM1) is an antibody-drug coupling drug, which can be used to treat HER2-positive breast cancer. EMILIA research shows that compared with capecitabine/lapatinib (XL) combined therapy, the experimental new drug T-DM 1 is well tolerated in 978 patients with HER2-positive metastatic breast cancer, and can significantly prolong the progression-free survival and overall survival. Due to the emergence of these new drugs, the median survival time of patients with HER2 positive metastatic breast cancer has been significantly improved in the past three years.

Management of bone metastasis of breast cancer

60%-80% of advanced breast cancer will have bone metastasis. Bone-related events include bone pain, fracture and spinal cord compression. Previous studies have confirmed that zoledronic acid can reduce the risk of complications of bone metastasis in breast cancer, and its principle is that zoledronic acid can inhibit osteoclast-mediated bone resorption.

Denosumab(XGEVA) is a monoclonal antibody injected subcutaneously. XGEVA can bind to RANKL, which is a transmembrane protein or soluble protein that is extremely important for the formation, function and survival of osteoclasts. In solid tumors with bone metastasis, RANKL stimulates the activity of osteoclasts, and XGEVA can prevent the activation of RANKL, thus preventing the occurrence of bone marrow-related events.

A recent randomized controlled study shows that XGEVA can reduce the incidence of bone marrow-related events more effectively than zoledronic acid. Both XGEVA and zoledronic acid can cause hypocalcemia, so calcium and vitamin D should be supplemented. The incidence of jaw necrosis in patients treated with XGEVA and zoledronic acid is 0.5%- 1%. Therefore, when taking such drugs, attention should be paid to maintaining oral hygiene and avoiding dental related operations as much as possible.

Management of brain metastasis of advanced breast cancer

As the survival time of breast cancer patients is obviously prolonged, the probability of brain metastasis is also increasing. The incidence of brain metastasis in HER-2 positive breast cancer is higher than that in HER-2 negative breast cancer, because most chemotherapy drugs, such as trastuzumab, cannot cross the blood-brain barrier.

Brain metastasis in patients with breast cancer usually indicates poor prognosis. For patients with multiple brain metastases, whole brain radiotherapy is the standard treatment. For patients with single or few brain metastases, tumor reduction surgery or stereotactic radiotherapy can be considered. Some patients with brain metastases from breast cancer can also achieve good results after treatment.