Preface
Recently, the American Society of Clinical Oncology (ASCO) released the 2024 Guidelines for Stratified Treatment of Systemic Therapy Resources for Metastatic Breast Cancer. Breast cancer is now one of the most common malignancies in the world, the fifth most common cause of cancer-related deaths, and remains the leading cause of cancer death among women worldwide, the guidelines state. The guidelines target adult patients with metastatic breast cancer (MBC) in resource-constrained settings and provide guidance to clinicians, public health leaders, patients, and policymakers on the best treatment options available.
The ASCO guidelines provide expert guidance on the treatment of patients with metastatic breast cancer, including first-, second- and third-line treatment options. Guidelines recommend different treatment regimens based on individual patient differences. In addition, the guidelines emphasize that pain management and palliative care should be provided to patients through the establishment of a coordinated health care system where resources are limited. In addition, the guidelines also introduce the relationship between breast cancer incidence and mortality and the Human Development Index (HDI), as well as the differences in breast cancer in different regions and stages, aiming to provide better services for cancer patients in resource-limited settings, and propose corresponding treatment strategies.
The Human Development Index (HDI) drives regional differences in breast cancer occurrence
HDI is a comprehensive index proposed by the United Nations Development Programme (UNDP) in the 1990 Human Development Report, which is a comprehensive indicator to measure the economic and social development level of United Nations member states based on the three basic variables of "life expectancy, education level and quality of life" according to certain calculation methods.
Data show that in 2020, breast cancer surpassed lung cancer for the first time as the world's most common malignancy, the fifth leading cause of cancer-related deaths, and remains the leading cause of cancer mortality among women worldwide. Of the 2.26 million new cases of breast cancer diagnosed in 2020, about 1.4 million cases were reported in low- and middle-income countries.
These statistics suggest that breast cancer incidence and mortality are higher in resource-constrained settings, and that breast cancer patients in resource-constrained settings are younger and have higher breast cancer mortality. Breast cancer incidence and mortality are inversely correlated with the Human Development Index.
Based on this situation, the guidelines recommend that specific public health policies be developed to provide evidence-based guidance for clinical practice, and that priority should be prioritized based on the patient's condition, treatment needs, and available resources, so as to develop individualized treatment plans and achieve effective allocation of resources.
Implement a four-level resource setup and develop ASCO resource tiering guidelines
In order to guide breast cancer treatment in different resource settings, ASCO has implemented a four-level resource setup, from which ASCO resource stratification guidelines have been developed. Emphasizing that disparities occur not only between different countries, but also within countries where disparities exist, for example, between rural and urban areas.
The method divides resources into four levels: Basic, Limited, Enhanced, and Maximal, as follows:
1. Basic resource setting: the minimum level of resources, including basic medical services and medicines;
2. Limited resource setting: including limited medical services and medicines, but more abundant than basic resource setting;
3. Enhanced resource setting: Include more abundant medical services and medicines, but less than the maximum resource setting;
4. Maximum resource setup: This includes state-of-the-art medical facilities and medications.
Table 1: Framework for resource tiering (guidance recommendations do not include maximum resources)
These updates are based on the ASCO Resource Stratification Guidelines to provide guidance for clinicians and policymakers in resource-constrained settings for metastatic breast cancer treatment, and note that the guidelines were developed to complement but not replace local guidelines.
Systemic therapy for metastatic breast cancer
Systemic treatment for adult patients with MBC includes first-, second- and third-line regimens. Palliative care aims to relieve symptoms and pain and improve quality of life.
1. First-line treatment of metastatic breast cancer
Table 2: Stratification strategies for first-line treatment of metastatic breast cancer
HR-positive patients:
Assessment of menopausal status is critical in patients with HR-positive MBC. In the basic case, if immunohistochemistry is not available, clinicians may assume positive HR and offer tamoxifen in most cases. For HR-positive, HER2-negative MBC patients, endocrine therapy alone is used when nonsteroidal aromatase inhibitors and CDK4/6 inhibitors are not available. For life-threatening disease, clinicians may use single-agent chemotherapy and surgery if resection is required for local control. Premenopausal patients with HR-positive, HER2-negative MBC should be given ovarian suppression or ablation plus endocrine therapy. Patients with HR-positive MBC taking endocrine medications before menopause may undergo ovarian ablation, combined with endocrine therapy in an augmentation resource setting, and alternative endocrine therapy or surgery in a limited setting. Patients receiving chemotherapy for HR-positive, HER2-negative MBC should be treated with single-agent chemotherapy rather than combination chemotherapy, and combination chemotherapy may be offered for severe symptomatic or life-threatening disease. Postmenopausal patients with HR-positive MBC can receive endocrine therapy or targeted therapy and single-agent chemotherapy. Patients with HR-positive MBC who are not receiving endocrine therapy before menopause can receive tamoxifen, or ovarian ablation or ovarian suppression alone, or sequential endocrine therapy, or nonsteroidal aromatase inhibitors with ovarian ablation or ovarian suppression and CDK4/6 inhibitors in an augmentation resource setting. In limited cases, tamoxifen or ovarian ablation in combination with endocrine therapy, tamoxifen is used in the basic setting.
HER2-positive patients:
HER2-targeted therapy is recommended for patients with HER2-positive advanced disease, except for those with clinically congestive heart failure or markedly impaired left ventricular ejection fraction, which should be evaluated on a case-by-case basis. First-line treatment with trastuzumab, pertuzumab, and taxane is recommended. If pertuzumab is not available, then clinicians can provide chemotherapy and trastuzumab in an augmentative resource setting. Chemotherapy is provided in a limited setting. For patients with HER2-positive and HR-positive MBC, a variety of anti-HER2-targeted therapies and chemotherapy or endocrine therapy, chemotherapy alone or endocrine therapy alone, are available, depending on the availability of anti-HER2 therapy.
Triple negative patients:
For patients with PD-L1-positive triple-negative MBC, immune checkpoint inhibitors can be added to chemotherapy as first-line therapy in an enhanced setting. In limited cases, most patients with triple-negative MBC can receive chemotherapy. Patients with triple-negative MBC who are PD-L1 negative should be given single-agent chemotherapy rather than combination chemotherapy as first-line therapy. PARP inhibitor therapy is available for patients with HR-negative, HER2-negative MBC harboring BRCA1 or BRCA2 mutations. Patients with HR-positive MBC and known BRCA mutations who are not treated with a PARP inhibitor may be treated with endocrine therapy with or without ovarian ablation.
2. Second-line treatment of metastatic breast cancer
Second-line therapy refers to the further treatment measures taken after a patient has failed to respond to first-line therapy or has developed resistance. Second-line treatment usually includes chemotherapy, targeted therapy, immunotherapy, etc., and the specific treatment options need to be selected according to the specific situation of the patient.
Table 3: Second-line therapy for metastatic breast cancer
HR-positive patients:
In an augmented resource setting, it is recommended to rely on prior therapy, e.g., prior endocrine therapy, and clinicians may offer second-line endocrine therapy, with or without targeted therapy (eg, CDK4/6 inhibitors or everolimus). In limited cases of prior endocrine therapy, clinicians may provide second-line endocrine therapy or otherwise chemotherapy.
HER2-positive patients:
HER2-targeted therapy should be given based on prior therapy and HR status. Second-line treatment may be trastuzumab or an alternative regimen. In limited cases, chemotherapy can be offered, and trastuzumab may be used if available. In the basic case, if the patient has been previously treated, and there is no medication and pathology, and there are symptoms, the clinician can provide primary surgery, including local control, for palliative care reasons. A second-line option is offered if the patient received adjuvant trastuzumab-based therapy less than 1 year prior to relapse.
HR阳性，BRCA1/2突变患者：
Patients with HR-positive MBC with BRCA1/2 mutations who have failed endocrine therapy can be offered PARP inhibitor therapy instead of chemotherapy, or chemotherapy if PARP inhibitors are not available.
Triple negative patients:
In the second line, clinicians can provide chemotherapy with or without PD-L1 checkpoint inhibitors. Patients with triple-negative MBC with BRCA1/2 mutations who have received prior chemotherapy may be treated with PARP inhibitors.
3. Third-line treatment of metastatic breast cancer
Table 4: Third-line therapy for metastatic breast cancer
HER2-positive patients:
In third-line therapy, clinicians should offer other HER2-targeted therapy combinations. Endocrine therapy should be offered to patients with HER2-positive HR-positive MBC, with the decision to add trastuzumab on a case-by-case basis.
Triple negative patients:
In third-line therapy, PARP inhibitor therapy is considered if BRCA1/2 is mutated, and if not available, then clinicians can provide chemotherapy and palliative care.
4. Palliative care
Palliative care is a treatment for people with advanced cancer that aims to relieve symptoms and pain and improve quality of life. Palliative care usually includes medications, radiation therapy, psychotherapy, etc. In the treatment of metastatic breast cancer, palliative care may or may not include radiation therapy to control symptoms. In the basic case, it is assumed that neither chemotherapy nor targeted therapy nor molecular testing will be available. According to the ASCO palliative care guidelines, a health care system that coordinates oncology care should be established to identify palliative care needs for patients and families, and to support specialists in providing care to patients with MBC in resource-constrained settings with the help of telecommunications. Pain management is very important in the palliative care of MBC patients, and it is necessary to analyze the treatment plan according to the diagnosis and staging of metastatic breast cancer patients.
Bibliography:
Al Sukhun S,Temin S,Barrios CH,et al. Systemic Treatment of Patients With Metastatic Breast Cancer: ASCO Resource-Stratified Guideline.JCO Glob Oncol. 2024.
Edited by Cassie
审校:Faline
Typesetting: Cassie
Execution: Uni
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