Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer
Publication Date: May 31, 2022
Last Updated: August 22, 2022
Key Points
Key Points
Human epidermal growth factor receptor 2 (HER2)-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis.
Treatment
Treatment
HER2+
First-Line
Recommendation 1.0
Clinicians should recommend HER2-targeted therapy-based combinations for first-line treatment, except for highly selected patients with estrogen receptor-positive (ER+) or progesterone receptor-positive (PgR+) and HER2-positive disease for whom clinicians may use endocrine therapy alone. (EB, , H, S)
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Recommendation 1.1
Clinicians should recommend the combination of trastuzumab, pertuzumab, and a taxane for first-line treatment, unless the patient has a contraindication to taxanes. (EB, B, H, S)
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Second-Line
Recommendation 2.0
If a patient’s HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy, clinicians should recommend second-line HER2-targeted therapy-based treatment. (EB, , H, S)
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Recommendation 2.1 (updated)
If a patient’s HER2-positive advanced breast cancer has progressed during or after first-line HER2-targeted therapy (and the patient has not received trastuzumab deruxtecan), clinicians should recommend trastuzumab deruxtecan as a second-line treatment. (EB, B, M, S)
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Third-Line
Recommendation 3.0
If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment, clinicians should recommend third-line or greater-line HER2-targeted therapy-based treatment. (EB, , I, M)
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Overall, there are a lack of head-to-head trials, therefore there is insufficient evidence to recommend one regimen over another. The patient and clinician should discuss differences in treatment schedules, routes, and toxicities during the decision-making process.
Options include the following:
Options include the following:
Recommendation 3.1 (updated)
If a patient’s HER2-positive advanced breast cancer has progressed during or after second-line or greater HER2-targeted treatment and the patient has already received pertuzumab and trastuzumab deruxtecan, clinicians should recommend third-line or greater HER2-targeted therapy-based treatment. (, , , )
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Recommendation 3.1.1 (updated)
If a patient has not received trastuzumab emtansine (T-DM1) in second-line, should offer T-DM1 regimen. (EB, B, H, S)
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Recommendation 3.1.2 (updated)
May offer tucatinib combined with trastuzumab and capecitabine. (EB, B, M, S)
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Recommendation 3.1.3 (updated)
May offer trastuzumab deruxtecan. (EB, B, M, S)
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Recommendation 3.1.4 (updated)
May offer neratinib combined with capecitabine. (EB, B, M, W)
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Recommendation 3.1.5
May offer lapatinib and trastuzumab. (EB, B, M, W)
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Recommendation 3.1.6
May offer lapatinib and capecitabine. (EB, B, M, W)
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Recommendation 3.1.7
May offer other combinations of chemotherapy and trastuzumab. (EB, B, M, W)
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Recommendation 3.1.8 (updated)
May offer margetuximab plus chemotherapy. (EB, B, M, W)
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Recommendation 3.1.9
If a patient has not received pertuzumab, clinicians may offer pertuzumab. (IC, B, Ins, W)
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Recommendation 3.2.0
May offer hormonal therapy (in patients with ER+ and/or PgR+ disease). (EB, B, M, W)
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Recommendation 3.2.1 (updated)
May offer abemaciclib combined with trastuzumab and fulvestrant. (EB, B, M, W)
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Timing, Dose, Schedule, and Duration
Recommendation 4.0
If a patient is receiving HER2-targeted therapy and chemotherapy combinations, the chemotherapy should continue for approximately 4–6 months (or longer) and/or to the time of maximal response, depending on toxicity and in the absence of progression. When chemotherapy is stopped, clinicians should continue the HER2-targeted therapy; no further change in the regimen is needed until the time of progression or unacceptable toxicities. (EB, , I, M)
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Recurrence
Recommendation 5.0
If a patient finished trastuzumab-based adjuvant treatment ≤12 months before recurrence, clinicians should follow the second-line HER2-targeted therapy-based treatment recommendations. (EB, , I, M)
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Recommendation 5.1
If a patient finished trastuzumab-based adjuvant treatment >12 months before recurrence, clinicians should follow the first-line HER2-targeted therapy-based treatment recommendations. (EB, , H, S)
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HER2+, ER+, PgR+
First-Line
Recommendation 6.0
If a patient’s cancer is hormone receptor-positive and HER2-positive, clinicians may recommend either: (, , , )
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Recommendation 6.0.1
HER2-targeted therapy plus chemotherapy. (EB, , H, S)
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Recommendation 6.0.2
Endocrine therapy plus trastuzumab or lapatinib (in selected cases). (EB, , M, S)
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Recommendation 6.0.3
Endocrine therapy alone (in selected cases). (EB, , I, W)
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Endocrine Therapy Sequencing
Recommendation 7.0
If the patient has started with a HER2-positive targeted therapy and chemotherapy combination, clinicians may add endocrine therapy to the HER2-targeted therapy when chemotherapy ends and/or when the cancer progresses. (IC, , Ins, W)
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First-Line Endocrine Therapy
Recommendation 8.0
In special circumstances, such as low disease burden, the presence of co-morbidities (contradictions to HER2-targeted therapy such as congestive heart failure), and/or the presence of a long disease free-interval, clinicians may offer first-line endocrine therapy alone. (IC, , Ins, W)
Qualifying Statement: Although the clinician may discuss using endocrine therapy with or without HER2-targeted, the majority of patients should still receive chemotherapy plus HER2-targeted therapy.
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Figure 1. Algorithm for Patients with HER2+ Advanced Disease
Notes:
If patient is receiving HER2-targeted therapy and chemotherapy combinations, give chemotherapy for 4–6 months or and/or to the time of maximal response, if low toxicity and no progression.
Continue HER2-targeted therapy after stoppage of chemotherapy.
a Except if contraindications to taxanes.
If patient is receiving HER2-targeted therapy and chemotherapy combinations, give chemotherapy for 4–6 months or and/or to the time of maximal response, if low toxicity and no progression.
Continue HER2-targeted therapy after stoppage of chemotherapy.
a Except if contraindications to taxanes.
Recommendation Grading
Abbreviations
- ASCO: American Society Of Clinical Oncology
- ER: Estrogen Receptor
- HER2: Human Epidermal Growth Factor Receptor 2
- PgR: Progesterone Receptor
- T-DM1: Trastuzumab Emtansine
Source Citation
Giordano SH, Franzoi MB, Temin S, et al. Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: ASCO Guideline Update. J Clin Oncol. 2022 May 31. doi: 10.1200/JCO.22.00519.
Disclaimer
This pocket guide is derived from recommendations in the American Society of Clinical Oncology Guideline. This resource is a practice tool based on ASCO® practice guidelines and is not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients. This pocket guide does not purport to suggest any particular course of medical treatment. Use of the practice guidelines and this resource are voluntary. The practice guidelines and additional information are available at www.asco.org/breast-cancer-guidelines. Copyright © 2022 by American Society of Clinical Oncology. All rights reserved.