Treatment

Document Overview

Design and created by Guideline Central in participation with the American Society of Clinical Oncology.

Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

American Society of Clinical Oncology

Publication Date: May 30, 2022

Page Last Updated: May 5, 2026

Grading Table

Recommendation Grading

Type		Benefit/harm		Evidence Quality		Strength of Recommendation
EB	Evidence-based	B	Benefits outweigh harms	H	High	Strong
CB/ FC	Consensus-based/ Formal Consensus	H	Harms outweigh benefits	M	Moderate	Moderate
IC	Informal consensus	B / H	Relative balance of benefits and harms	I	Intermediate	Weak
		U	Benefits/harms ratio uncertain	L	Low
				VL	Very Low
				Ins	Insufficient

Recommendation Rating Definitions

Quality of Evidence

Term	Definitions
H = High	We are very confident that the true effect lies close to that of the estimate of the effect
M = Moderate	We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
L = Low	Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
VL = Very low	We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect.

Strength of Recommendation

Term	Definitions
S = Strong	In recommendations for an intervention, the desirable effects of an intervention outweigh its undesirable effects. In recommendations against an intervention, the undesirable effects of an intervention outweigh its desirable effects. All or almost all informed people would make the recommended choice for or against an intervention.
C = Conditional/ W = Weak	In recommendations for an intervention, the desirable effects probably outweigh the undesirable effects, but appreciable uncertainty exists. In recommendations against an intervention, the undesirable effects probably outweigh the desirable effects, but appreciable uncertainty exists. Most informed people would choose the recommended course of action, but a substantial number would not.

Brozek JL, Akl EA, Compalati E, et al: Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations. Allergy 66:588-95, 2011

Document Overview

Document Title: Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Authoring Society: American Society of Clinical Oncology

Document Publication Date: May 30, 2022

Page Last Reviewed/Updated: May 5, 2026

Document Type: Guideline

Country of Publication: United States

Full Text Freely Available: Yes

Full Text Guideline: ascopubs.org/doi/full/10.1200/JCO.22.00519

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.

Supplemental Implementation Resources

Document Scope, Criteria, and Use Cases

Document Objectives: The purpose of this guideline update is to provide oncologists, other health care practitioners, patients, and caregivers with recommendations regarding guidance for optimal management of patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC).

Scope: Treatment

Diseases/Conditions (MeSH)

D001943 - Breast Neoplasms

Keywords: Advanced Breast Cancer, HER2, HER2 Positive, breast cancer, human epidermal growth factor receptor 2 (HER2)

Target Patient Population: Individuals with advanced HER2-positive breast cancer.

Target Provider Population: Medical oncologists, radiation oncologists, surgeons, oncology nurses

Inclusion Criteria: Female, Adult, Older Adult

Health Care Settings: Ambulatory, Hospital, Outpatient

Intended Users: Nurse, Nurse Practitioner, Physician, Physician Assistant

Recommendation Development Processes & Methodology

PICO Questions

What is the optimal treatment for patients with HER2-positive advanced breast cancer?
What is the optimal medical therapy for advanced human epidermal growth factor receptor 2 (HER2)–positive breast cancer in combination with chemotherapy and/or endocrine therapy?

Supplemental Methodology Resources: Data Supplement Evidence Tables

Number of Source Documents: 51

Literature Search Start Date: Sunday, July 31, 2016

Literature Search End Date: Wednesday, March 31, 2021

Includes peer/external review process?: Yes

Includes public comment process?: Yes

Methodologist involvement?: Yes

Patient involvement?: No

Includes multi-disciplinary group?: Yes

Includes systematic review?: Yes

Grades quality of strength of evidence?: Yes

Grades quality of strength of recommendation?: Yes

Discloses funding source?: Yes

Discloses conflicts of interest?: Yes

Includes benefits/harms analysis with recommendations?: No

Systemic Therapy for Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Treatment

HER2+

First-Line

Recommendation 1.0

Recommendation 1.1

Second-Line

Recommendation 2.0

Recommendation 2.1 (updated)

Third-Line

Recommendation 3.0

Recommendation 3.1 (updated)

Recommendation 3.1.1 (updated)

Recommendation 3.1.2 (updated)

Recommendation 3.1.3 (updated)

Recommendation 3.1.4 (updated)

Recommendation 3.1.5

Recommendation 3.1.6

Recommendation 3.1.7

Recommendation 3.1.8 (updated)

Recommendation 3.1.9

Recommendation 3.2.0

Recommendation 3.2.1 (updated)

Timing, Dose, Schedule, and Duration

Recommendation 4.0

Recurrence

Recommendation 5.0

Recommendation 5.1

HER2+, ER+, PgR+

First-Line

Recommendation 6.0

Recommendation 6.0.1

Recommendation 6.0.2

Recommendation 6.0.3

Endocrine Therapy Sequencing

Recommendation 7.0

First-Line Endocrine Therapy

Recommendation 8.0

Grading Table

Recommendation Grading

Recommendation Rating Definitions

Quality of Evidence

Strength of Recommendation

Document Overview

Supplemental Implementation Resources

Document Scope, Criteria, and Use Cases

Recommendation Development Processes & Methodology