HER2-low and HER2-ultralow metastatic breast cancer: lines of therapy

Cancer page →

4 standard-of-care settings across 2 lines and 3 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers	HER2-low	HR-positive
Second line	·	1	1
Other settings	1	1	·

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
HER2-low	After one or two lines of chemotherapy	Trastuzumab deruxtecan for HER2-low disease of either hormone receptor status (DESTINY-Breast04).	Trastuzumab deruxtecanDESTINY-Breast04HER2-low and HER2-ultralow		97
HR-positive	Hormone receptor-positive, after endocrine therapy, chemotherapy-naive	Trastuzumab deruxtecan ahead of chemotherapy for HER2-low or ultralow disease (DESTINY-Breast06).	Trastuzumab deruxtecanDESTINY-Breast06HER2-low and HER2-ultralow		97

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Lung toxicity	Baseline and interval CT, prompt corticosteroids and permanent discontinuation for grade 2 or higher interstitial lung disease.	CT (computed tomography)Interstitial lung disease (ILD) / pneumonitis		66
HER2-low	Triple-negative HER2-low disease	TROP2 antibody-drug conjugates first (ASCENT, TROPION-Breast02), trastuzumab deruxtecan as a later option.	Sacituzumab govitecanDatopotamab deruxtecanASCENTTROPION-Breast02Trastuzumab deruxtecan		97

Sequence and caution pairings

CautionApproved

Caution: DXd ADC + agents with pneumonitis risk

Enhertu and its DXd cousins can inflame the lungs; combining them with immunotherapy, radiation, or mTOR inhibitors stacks that risk.

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.