Systemic Treatment of Patients With Metastatic Breast Cancer: ASCO Resource–Stratified Guideline Q and A

Abstract

The Systemic Treatment of Patients with Metastatic Breast Cancer: @ASCO Resource-Stratified Guideline Q and A presents takeways, rationale, and key recommendations based on #JCOGO full guideline for patients by menopausal and marker status.

In 2024, ASCO published a guideline for clinicians, patients, and policymakers in resource-constrained settings on the treatment of patients with metastatic breast cancer (MBC).¹ The purpose of that guideline is to provide expert guidance on the systemic treatment of MBC to clinicians, public health leaders, patients, and policymakers in resource-constrained settings (Appendix Table A1). The guideline's target population is adult patients with MBC in resource-constrained settings and focuses on medical treatment. The guideline is not intended for patients in Maximal settings.

QUESTION: WHY ARE RESOURCE-STRATIFIED GUIDELINES FOR MANAGEMENT OF PATIENTS WITH MBC NEEDED?

More than half of patients diagnosed with breast cancer worldwide are in regions with limited healthcare resources where access to the most effective treatment may be limited and may vary significantly between healthcare settings and populations. The resource-stratified guidelines aim to address the main challenges of delivering best practice care in the context of such limitations in two ways—first, by providing a framework for healthcare providers that outlines a rational, evidence-based approach to the selection of best treatments in the context of resource limitations (Table 1). Second, these guidelines aim to assist the health systems in identifying the goals for improvement in access to treatments that are the most effective and equitable.

TABLE 1.

Summary of Key Guideline Recommendations

Applying guidelines to the management of patients with MBC presents some unique challenges. Unlike other cancer care interventions that depend on capital infrastructure (such as surgery or screening programs), significant aspects of the management of patients with MBC involve systemic therapies such as hormonal therapy, chemotherapy, or targeted therapy. These agents can be increasingly sourced by patients themselves, and there is significant variation in access that may change rapidly over time, depending on market forces and supply. Accordingly, limitations in resources are not static and require that healthcare providers adopt a flexible, evidence-based, and patient-centered approach.

QUESTION: WHAT ARE THE MAIN TAKEAWAYS?

The approach to the management of patients with MBC should be guided by the pathological features of the tumor, patients' palliative care needs, and available evidence-based, effective treatment. Within the resource constraints, clinicians should select the most effective accessible treatments with the input of the multidisciplinary care team. Patients' preferences and consideration of any potential financial toxicity need to be considered, especially in settings where the gains in efficacy from costly therapies may be marginal. Research of cancer therapies, including the study of patient-reported outcomes and patients' preferences, conducted in resource-constrained settings should be a priority to build the evidence base.

QUESTION: WHAT IS THE RECOMMENDED FRONTLINE TREATMENT FOR PATIENTS WITH HORMONE RECEPTOR–POSITIVE MBC?

Hormonal therapy is the cornerstone of management for patients with hormone receptor–positive cancer. The type of hormonal therapy depends on the menopausal status of the patient. For patients who are premenopausal, therapy includes ovarian ablation, either by medical, surgical, or radiation means (see the section on Recommended Treatment for Premenopausal Patients with MBC for more). For patients who are postmenopausal, aromatase inhibitors (AIs) with or without CDK4/6 inhibitors can be used where available. Patients with high volume of hormone receptor–positive visceral disease where the risk of visceral crisis is a concern may be offered chemotherapy as an initial treatment.

QUESTION: WHAT IS THE RECOMMENDED TREATMENT FOR PATIENTS WITH HER2-POSITIVE MBC?

Human epidermal growth factor receptor 2 (HER2)–targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with cardiovascular contraindications. In special circumstances, such as low disease burden, and/or the presence of a long disease free-interval, clinicians may offer first-line endocrine therapy alone.

When treating patients with HER2-positive MBC, trastuzumab, pertuzumab, and a taxane, or endocrine therapy for first-line treatment are recommended according to ASCO guidelines. However, in resource-constrained settings, the resource-stratified guideline presents a tiered list of alternatives. For example, if pertuzumab isn't available, then clinicians may offer either chemotherapy plus trastuzumab, or chemotherapy. Trastuzumab emtansine, capecitabine plus lapatinib, chemotherapy or endocrine therapy plus trastuzumab, or either without trastuzumab if the latter is not available. Navelbine can be used with trastuzumab in the frontline setting, if taxanes are not available. Another possible companion is platinum therapy.

In the second-line setting, or relapse within 12 months of adjuvant therapy, HER2-targeted therapy should be given based on prior therapy, hormone receptor status, and availability. While trastuzumab deruxtecan is the Maximal setting–recommended second-line option, in resource-constrained settings where patients and clinicians cannot access the most resource-required targeted therapy, chemotherapy or endocrine therapy may be offered with or without alternate HER2-targeted therapy regimens. The alternatives are again listed in a tiered order.

QUESTION: WHAT IS THE RECOMMENDED TREATMENT FOR PATIENTS WITH TRIPLE-NEGATIVE MBC?

Patients with triple-negative, PD-L1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment in Limited as well as Enhanced settings. However, for patients with symptomatic or immediate life-threatening disease, combination therapy, if possible, may be offered.

In the second-line setting, with or without prior PD-L1 checkpoint inhibitors, clinicians may offer palliative or best supportive care in the Basic setting; chemotherapy with anthracyclines, taxanes, or carboplatin in the Limited setting and chemotherapy, if sacituzumab govitecan is unavailable, in the Enhanced setting. In the third-line setting, for patients with triple-negative MBC, clinicians may offer chemotherapy and/or palliative care.

QUESTION: WHAT IS THE RECOMMENDED TREATMENT FOR PATIENTS WITH MBC AND UNKNOWN RECEPTOR STATUS?

In Basic settings, if no immunohistochemistry testing is available, clinicians may presume hormone receptor positivity and offer tamoxifen in most cases. This is based on the higher prevalence of hormone receptor–positive tumors worldwide and the relatively low toxicity of tamoxifen. Another alternative is single-agent chemotherapy. Combination regimens may be offered for symptomatic or immediately life-threatening disease for which time may allow only one potential chance for therapy. Clinicians may offer primary surgery for palliative reasons, including local control.

QUESTION: WHAT IS THE RECOMMENDED TREATMENT FOR PATIENTS WITH MBC WHOSE CANCER IS PD-L1–POSITIVE OR BRCA1/2 MUTATION–POSITIVE OR HORMONE RECEPTOR–POSITIVE?

The guideline presents treatment options for patients with MBC and positive PD-L1 or BRCA1/2 status. For germline BRCA1/2 mutation–positive MBC, if poly ADP-ribose polymerase inhibitor (PARPi) is unavailable, clinicians may use hormonal therapy (hormone receptor–positive MBC; with or without ovarian ablation) and chemotherapy (hormone receptor–negative MBC) in the first-line setting. In second-line setting, patients with triple-negative MBC with germline BRCA1/2 mutations who previously received chemotherapy may be offered a PARPi rather than chemotherapy, if available. But clinicians should not offer these unless the patient has a known germline BRCA mutation.

This resource-stratified guideline and related ASCO guidelines present treatment for patients with these diagnoses, when quality-assured pathology results are available to guide the selection of targeted therapy, which are not yet available in many Basic and Limited Settings. The authors refer readers to the full guidelines.

QUESTION: WHAT IS THE RECOMMENDED TREATMENT FOR PATIENTS WITH MBC WHO ARE PREMENOPAUSAL THAT’S UNIQUE AS COMPARED TO THOSE WHO ARE POSTMENOPAUSAL?

When treating patients who are premenopausal, the same recommendations apply as in the case of postmenopausal patients, with one caveat. Whenever hormonal therapy—besides tamoxifen—is indicated, ovarian ablation is a prerequisite. It is recommended in addition to any modality used for treatment and can be combined with either tamoxifen or an AI, depending on availability and patients' tolerance. Surgical oophorectomy or radiotherapy ablation (when available) should be recommended rather than medical ovarian suppression strategies. For those patients who cannot tolerate ovarian ablation, tamoxifen is a reasonable alternative. Only surgeons with gynecologic surgical expertise should perform oophorectomies.

QUESTION: WHAT IS THE ROLE OF PRIMARY TUMOR SURGERY IN MBC?

Primary tumor surgery in appropriately selected patients with de novo stage IV breast cancer controls locoregional progression, but interpretation of the limited evidence continues regarding its impact on overall survival in patients with oligometastatic or bone-only disease. Until the Expert Panel has further prospective data, especially when medical therapy resources are constrained, surgery of the primary tumor in appropriately selected patients with limited disease burden, bone-only disease, and estrogen receptor–positive and/or HER2-positive disease, who can attain a negative margin on surgery especially those younger than 55 years, is recommended. The Panel acknowledges the controversy surrounding this recommendation and advises discussion with the patient, emphasizing the palliative benefit and the potentially positive impact. In addition, the Expert Panel suggests palliative mastectomy for patients with bleeding or progressively ulcerating tumors not responding to systemic therapy, especially in Basic or Limited settings; whenever radiation therapy is not available.

APPENDIX

TABLE A1.

Framework of Resource Stratification

AUTHOR CONTRIBUTIONS

Conception and design: Sana Al Sukhun, Bogda Koczwara, Sarah Temin, Banu K. Arun

Administrative support: Sana Al Sukhun, Sarah Temin, Banu K. Arun

Collection and assembly of data: All authors

Data analysis and interpretation: All authors

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/go/authors/author-center.

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