Breast Cancer – Metastatic Disease

Oligometastatic breast cancer usually means up to 5 metastatic lesions in the same or different organ sites. These patients may be considered for definitive therapy with curative intent, potentially including surgery or ablative therapy.

The algorithm provides guidelines for the evaluation and treatment of metastatic breast cancer at MD Anderson, using a multidisciplinary approach tailored to the institution's patient population, services, and structure. It is not intended to replace independent medical judgment.

No, the algorithm specifically states it should not be used to treat pregnant women.

Recommended evaluations include biopsy for confirmation and determination of ER/PR/HER2 status, tumor genomic analysis, CT with contrast or PET/CT/MRI, surgical and radiation oncology consult as indicated, CBC with chemistries, tumor markers (as adjunct), assessment of symptoms and metastatic sites, genetic testing, lifestyle risk assessment, and discussion of Goal Concordant Care.

All metastatic breast cancer patients, regardless of subtype and family history, should have genetic testing performed via referral to Clinical Genetics or provider-ordered genetic testing pathway.

Patients with bone metastases and life expectancy over 12 weeks should receive a bisphosphonate (if creatinine clearance ≥30 mL/min) or denosumab after dental evaluation, in addition to anti-cancer therapy.

First-line therapy is an aromatase inhibitor (AI) or fulvestrant with a CDK4/6 inhibitor (ribociclib or abemaciclib). If prior AI therapy within one year, consider fulvestrant plus CDK4/6 inhibitor.

Targeted therapies include fulvestrant with alpelisib or capivasertib (for PIK3CA/AKT1/PTEN mutations), elacestrant (for ESR1 mutation), larotrectinib or entrectinib (for NTRK fusion), pembrolizumab or dostarlimab (for MSI-H/dMMR), selpercatinib (for RET fusion), dabrafenib and trametinib (for BRAF V600E), and neratinib/fulvestrant/trastuzumab (for HER2 mutation).

If no prior trastuzumab or >6 months since adjuvant trastuzumab, docetaxel or paclitaxel plus trastuzumab and pertuzumab are recommended. For select patients, AI with trastuzumab or trastuzumab/lapatinib, or trastuzumab+pertuzumab+AI.

Paclitaxel (or docetaxel) plus trastuzumab and pertuzumab is first-line if no prior trastuzumab or >6 months since adjuvant trastuzumab.

Fam-trastuzumab deruxtecan-nxki is recommended after at least one line of systemic chemotherapy in the metastatic setting for HER2-low tumors.

Pembrolizumab plus chemotherapy (albumin-bound paclitaxel, paclitaxel, or gemcitabine/carboplatin) is recommended if PD-L1 is present.

Scenarios include oligometastasis, Stage IV NED, brain metastases, leptomeningeal disease, choroid metastases, cord compression, plexopathy/radiculopathy, extensive loco-regional disease, pathologic/impending pathologic fracture, pleural/pericardial effusion, SVC syndrome, biliary/ureteral obstruction, pregnancy, and de novo M1 inflammatory breast cancer.

Preferred single agents include doxorubicin, pegylated liposomal doxorubicin, paclitaxel, albumin-bound paclitaxel, capecitabine, gemcitabine, vinorelbine, eribulin, carboplatin, and sacituzumab govitecan-hziy.

The ECOG performance status is a scale from 0 (fully active) to 5 (dead) used to assess a patient's level of functioning and ability to tolerate cancer therapy, guiding treatment decisions.

Surgery is generally not recommended in stage IV disease except within clinical trials or in select cases such as patients with oligometastatic disease and excellent response to systemic therapy.

For oligometastatic disease, radiation may target both the primary and metastatic sites, and enrollment in clinical trials is encouraged. In widely metastatic disease, radiation is palliative and site-specific.

Options include switching to another endocrine therapy (e.g., fulvestrant, exemestane, tamoxifen, everolimus, abemaciclib if not previously given), capivasertib, targeted therapies for actionable mutations, or chemotherapy agents as per Appendix B.

Options include fam-trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, tucatinib with trastuzumab and capecitabine, capecitabine plus lapatinib or neratinib, margetuximab-cmkb plus chemotherapy, or trastuzumab with other chemotherapies.

PD-L1 is assessed using immunohistochemical assay 22C3, and considered positive if the combined positive score (CPS) is ≥10.

For BRCA1/2 or PALB2 germline mutations, PARP inhibitors like talazoparib or olaparib are recommended.

Oligometastatic breast cancer usually means up to 5 metastatic lesions in the same or different organ sites. These patients may be considered for definitive therapy with curative intent, potentially including surgery or ablative therapy.

The algorithm provides guidelines for the evaluation and treatment of metastatic breast cancer at MD Anderson, using a multidisciplinary approach tailored to the institution's patient population, services, and structure. It is not intended to replace independent medical judgment.