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Last reviewed: 20 Apr 2025
Last updated: 24 Apr 2025

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • bone pain
  • pleural effusion
  • palpable mass after treatment of the primary tumour
Full details

Other diagnostic factors

  • shortness of breath
  • cough (non-productive)
  • anorexia
  • weight loss
  • neurological 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)
  • tumour >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 non-polyposis colorectal cancer)
  • CHEK2 mutations
  • ATM mutations
  • minimal residual disease (MRD)
  • bone metastasis and lung metastasis gene signatures
Full details

Diagnostic investigations

1st investigations to order

  • FBC
  • LFTs
  • calcium
  • CT (of chest and abdomen)
  • bone scan (scintigraphy)
Full details

Investigations 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
  • multi-gated acquisition (MUGA) scan
  • pleural cytology
Full details

Treatment algorithm

ONGOING

hormone receptor-positive, HER2-negative, without visceral crisis: post-menopausal

hormone receptor-positive, HER2-negative, without visceral crisis: pre-menopausal

hormone receptor-positive, HER2-positive, without visceral crisis: post-menopausal

hormone receptor-positive, HER2-positive, without visceral crisis: pre-menopausal

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
Edward Sauter

Medical and Program Officer

Division of Cancer Prevention

National Cancer Institute

Rockville

MD

Disclosures

ES declares that he has no competing interests.

Wajeeha Razaq, MD

​Breast Cancer Site Chair

University Oklahoma School of Medicine

Oklahoma City

OK

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

UK

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

AL

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 here.

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