Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative

Publication Date: January 10, 2023
Last Updated: May 10, 2023

Treatment

New Recommendation from 2023 Guideline Rapid Recommendation Update

Patients with hormone receptor-positive HER2-negative metastatic breast cancer who are refractory to endocrine therapy and have received at least 2 prior lines of chemotherapy for metastatic disease may be offered sacituzumab govitecan. (Quality of Evidence - Medium) ( EB , , B , S )
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New Recommendation from 2022 Guideline Rapid Recommendation Update

Patients with HER2 IHC 1+ or 2+ and ISH negative metastatic breast cancer who have received at least one prior chemotherapy for metastatic disease, and if HR+ are refractory to endocrine therapy, should be offered treatment with trastuzumab deruxtecan. (Quality of Evidence - Moderate) ( EB , , B , S )
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Patients with metastatic triple negative breast cancer with expression of programmed cell death ligand-1 (PD-L1-positive) and no existing contraindications may be offered the addition of immune checkpoint inhibitor to chemotherapy (atezolizumab plus nab-paclitaxel or pembrolizumab plus chemotherapy) as first-line therapy. ( EB , I , B , S )
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Patients with metastatic triple negative breast cancer without expression of programmed cell death ligand-1 (PD-L1-negative) should be offered single agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for symptomatic or immediately life-threatening disease for which time may allow only one potential chance for therapy. ( EB , I , B , S )
Practical Information: Patients may be offered either platinum- or non-platinum-based regimens based on individualized patient and provider assessment of preferences, risks, and benefits.
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Patients with metastatic triple negative breast cancer who have received at least two prior therapies for metastatic disease should be offered treatment with sacituzumab govitecan. ( EB , H , B , S )
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Patients with metastatic triple negative breast cancer with germline BRCA1 or 2 mutations who have previously been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic disease setting may be offered an oral PARP inhibitor (olaparib or talazoparib) rather than chemotherapy. ( EB , I , B , S )
Practical Information: Small single-arm studies show that oral PARP inhibitor therapy demonstrates high response rates in metastatic breast cancer encoding DNA repair defects, such as germline PALB2 mutation carriers and somatic BRCA mutations. It should also be noted that the randomized PARP inhibitor trials made no direct comparison with taxanes, anthracyclines, or platinums. Comparative efficacy against these compounds is unknown.
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Patients with metastatic hormone receptor-positive (HR-positive) breast cancer with disease progression on a prior endocrine agent with or without targeted therapy may be offered treatment with either endocrine therapy with or without targeted therapy (refer to the companion ASCO guideline on Endocrine Therapy and Targeted Therapy for Hormone Receptor-Positive, HER2-negative Metastatic Breast Cancer [Burstein et al. J Clin Oncol. doi: 10.1200/JCO.21.01392] for details) or single-agent chemotherapy. ( EB , I , B , S )
Practical Information: Treatment choice should be based on individualized patient and provider assessment of preferences, risks, and benefits.
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Patients with metastatic HR-positive but HER2-negative breast cancer with germline BRCA1 or 2 mutations who are no longer benefiting from endocrine therapy may be offered an oral PARP inhibitor in the first- through to third-line setting rather than chemotherapy. ( EB , I , B , S )
Practical Information: Small single-arm studies show that oral PARP inhibitor therapy demonstrates high response rates in metastatic breast cancer encoding DNA repair defects, such as germline PALB2 mutation carriers and somatic BRCA mutations. It should also be noted that the randomized PARP inhibitor trials made no direct comparison with taxanes, anthracyclines, or platinums. Comparative efficacy against these compounds is unknown.
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Patients with HR-positive HER2-negative metastatic breast cancer no longer benefiting from endocrine therapy should be offered single agent chemotherapy rather than combination therapy, although combination regimens may be offered for symptomatic or immediately life-threatening disease for which time may allow only one potential chance for therapy. ( EB , I , B , S )
Practical Information: Choice of chemotherapy agent should be based on individualized patient and provider assessment of preferences, risks, and benefits.
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No recommendation regarding at which point a patient’s care should be transitioned to hospice or best supportive care only is possible at this time. ( CB , , U, S )
Practical Information: Given the heterogeneity of breast cancer and the treatment goals of patients with breast cancer, it is not possible to identify a universal optimal time to transition to hospice or best supportive care. When to transition is a decision that should be shared between the patient and clinician in the context of an ongoing conversation regarding goals of care. The conversation about integration of supportive care and eventual consideration of hospice care should start early in the management of metastatic breast cancer.
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Recommendation Grading

Overview

Title

Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative

Authoring Organization

Publication Month/Year

January 10, 2023

Last Updated Month/Year

March 20, 2024

Document Type

Guideline

Country of Publication

US

Target Patient Population

Women or men with HER2-negative MBC that is HR-positive but endocrine-pretreated or triple negative.

Target Provider Population

Health care providers (including primary care physicians, specialists, nurses, social workers, and any other relevant member of a comprehensive multidisciplinary cancer care team

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D018567 - Breast Neoplasms, Male, D001943 - Breast Neoplasms

Keywords

breast cancer, chemotherapy, Metastatic Breast Cancer, Targeted Therapy

Source Citation

Moy B, Rumble RB, Come S et al. Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2023 January 10. doi: 10.1200/JCO.22.02807

Moy B, Rumble RB, Come S et al. Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2022 August 4. doi: 10.1200/JCO.22.01533

Moy B, Rumble RB, Come S et al. Chemotherapy and Targeted Therapy for Patients With Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That is Either Endocrine-Pretreated or Hormone Receptor–Negative: ASCO Guideline Update. J Clin Oncol. 2021;39(35):3938-3958. doi:10.1200/jco.21.01374.

Supplemental Methodology Resources

Evidence Tables