Metastatic breast cancer

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 26 Jun 2025

Last updated: 24 Apr 2025

Metastatic breast cancer (MBC) demonstrates great heterogeneity in both presentation and prognosis.

The diagnostic approach for MBC involves identification of risk factors, a full clinical history and physical exam, laboratory investigations, imaging studies, and assessment of tumor biomarker status (where feasible).

Potential goals of therapy are to maximize progression-free and overall survival, reduce tumor-related symptoms, enhance/maintain performance status, preserve or improve quality of life, and minimize toxicity.

Biomarkers may be used to guide therapy.

Systemic therapy (i.e., hormone therapy, chemotherapy, immunotherapy, targeted therapy) is the standard approach for managing MBC.

Treatment should be individualized, based on patient prognosis, tumor characteristics, biomarker status, performance status, and the primary goals of treatment.

Definition

Breast cancer is considered metastatic breast cancer (MBC) if the disease has spread beyond the breast and ipsilateral lymph nodes (axillary, internal mammary, infra- and supraclavicular).[1]

History and exam

Key diagnostic factors

bone pain
pleural effusion
palpable mass after treatment of the primary tumor

Full details

Other diagnostic factors

shortness of breath
cough (nonproductive)
anorexia
weight loss
neurologic symptoms (e.g., neuralgic pain, weakness, headaches, seizures)

Full details

Risk factors

female sex
age >50 years
family history of breast, ovarian, pancreatic, and/or prostate cancer
breast cancer susceptibility genes (BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, and TP53)
tumor >5 cm in diameter
high number of positive axillary lymph nodes (e.g., >10)
lymphovascular invasion
high-risk 70-gene signature
high-risk 21-gene signature
high-risk PAM50 gene signature
Lynch syndrome (hereditary nonpolyposis colorectal cancer)
CHEK2 mutations
ATM mutations
minimal residual disease (MRD)
bone metastasis and lung metastasis gene signatures

Full details

Diagnostic tests

1st tests to order

CBC
LFTs
calcium
CT (of chest and abdomen)
bone scan (scintigraphy)

Full details

Tests to consider

MRI (focused on area of concern, e.g., brain, spinal cord, bone)
FDG-PET/CT scan
biopsy of metastatic lesion
germline testing for high-penetrance breast cancer susceptibility genes
additional biomarker testing
echocardiogram
multigated acquisition (MUGA) scan
pleural cytology

Full details

Treatment algorithm

ONGOING

hormone receptor-positive, HER2-negative, without visceral crisis: postmenopausal

hormone receptor-positive, HER2-negative, without visceral crisis: premenopausal

hormone receptor-positive, HER2-positive, without visceral crisis: postmenopausal

hormone receptor-positive, HER2-positive, without visceral crisis: premenopausal

hormone receptor-negative, HER2-positive, without visceral crisis

PD-L1-negative, triple-negative (hormone receptor-negative, HER2-negative), without visceral crisis

PD-L1-positive, triple-negative (hormone receptor-negative, HER2-negative), without visceral crisis

hormone receptor-positive or negative, HER2-negative, with visceral crisis

hormone receptor-positive or negative, HER2-positive, with visceral crisis

Contributors

Authors

Edward Sauter, MD, PhD

Medical and Program Officer

Division of Cancer Prevention

National Cancer Institute

Rockville

Disclosures

ES declares that he has no competing interests.

Wajeeha Razaq, MD

Breast Cancer Site Chair

University Oklahoma School of Medicine

Oklahoma City

Disclosures

WS declares that she has no competing interests.

Acknowledgements

Dr Edward Sauter and Dr Wajeeha Razaq would like to gratefully acknowledge Dr Puja Nistala, Dr Donald Doll, Dr Carl E. Freter and Dr Michael Perry, previous contributors to this topic.

Disclosures

PN, DD, CEF and MP declare that they have no competing interests.

Peer reviewers

Alan Neville, MD

Professor

Assistant Dean

Undergraduate Program

McMaster University

Hamilton

Ontario

Canada

Disclosures

AN declares that he has no competing interests.

Gianfilippo Bertelli, MD, PhD, FRCP (Edin)

Consultant

Honorary Senior Lecturer in Medical Oncology

South West Wales Cancer Centre

Swansea

Disclosures

GB has received honoraria for participation in advisory boards (AstraZeneca, Novartis, Pfizer, Roche, GSK, Cephalon, Amgen, Sanofi, Aventis), speaker's fees (AstraZeneca, Novartis, Sanofi, Aventis), and hospitality at conferences (AstraZeneca, Novartis, Pfizer, Roche, Aventis).

Christos Vaklavas, MD

Assistant Professor

Division of Hematology/Oncology

Department of Medicine

University of Alabama at Birmingham

Birmingham

Disclosures

CV declares that University of Alabama at Birmingham has received research support from Pfizer, F. Hoffmann-La Roche, and Incyte.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Gennari A, André F, Barrios CH, et al. ESMO clinical practice guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021 Dec;32(12):1475-95.Full text Abstract

National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].Full text

Rugo HS, Rumble B, Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol. 2016 Sep 1;34(25):3069-103.Full text Abstract

Giordano SH, Franzoi MAB, Temin S, et al. Systemic therapy for advanced human epidermal growth factor receptor 2-positive breast cancer: ASCO guideline update. J Clin Oncol. 2022 Aug 10;40(23):2612-35.Full text Abstract

Van Poznak C, Somerfield MR, Barlow WE, et al. Role of bone-modifying agents in metastatic breast cancer: an American Society of Clinical Oncology-Cancer Care Ontario focused guideline update. J Clin Oncol. 2017 Dec 10;35(35):3978-86.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Lung cancer
- Osteosarcoma
- Breast sarcoma
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Guidelines
- NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, pancreatic, and prostate
- NCCN clinical practice guidelines in oncology: breast cancer
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Patient information
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Metastatic breast cancer

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

hormone receptor-positive, HER2-negative, without visceral crisis: postmenopausal

hormone receptor-positive, HER2-negative, without visceral crisis: premenopausal

hormone receptor-positive, HER2-positive, without visceral crisis: postmenopausal

hormone receptor-positive, HER2-positive, without visceral crisis: premenopausal

hormone receptor-negative, HER2-positive, without visceral crisis

PD-L1-negative, triple-negative (hormone receptor-negative, HER2-negative), without visceral crisis

PD-L1-positive, triple-negative (hormone receptor-negative, HER2-negative), without visceral crisis

hormone receptor-positive or negative, HER2-negative, with visceral crisis

hormone receptor-positive or negative, HER2-positive, with visceral crisis

Contributors

Authors

Edward Sauter, MD, PhD

Disclosures

Wajeeha Razaq, MD

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Alan Neville, MD

Disclosures

Gianfilippo Bertelli, MD, PhD, FRCP (Edin)

Disclosures

Christos Vaklavas, MD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice