Breast cancer

Spread and metastases

Deputy Editor-in-Chief: Debra L. Zynger, M.D.
Emily S. Reisenbichler, M.D.

Last author update: 1 May 2018
Last staff update: 5 July 2022

Copyright: 2002-2022,, Inc.

PubMed Search: Spread and metastases[TI] breast[TI] full text[sb]

Emily S. Reisenbichler, M.D.
Page views in 2021: 2,326
Page views in 2022 to date: 1,147
Cite this page: Reisenbichler ES Spread and metastases. website. Accessed July 5th, 2022.
Definition / general
  • See also Staging topic
  • Breast carcinoma spreads by axillary, interpectoral and internal mammary lymphatic and vascular channels first to regional lymph nodes
  • Regional lymph nodes for breast carcinoma include ipsilateral intramammary, internal mammary, axillary and supraclavicular lymph nodes for staging purposes (pN)
  • Metastases to any other lymph nodes, including cervical or contralateral internal mammary or contralateral axillary lymph nodes, are considered distant metastases for staging purposes (pM)
  • Additional sites of distant metastases vary depending on tumor type and receptor status but most often include bone, lung, brain and liver
  • Circulating tumor cells or incidental tumor deposits (≤ 0.2 mm) called microscopic tumor cells do not constitute metastatic disease
Essential features
ICD coding
  • C77.3: Secondary and unspecified malignant neoplasm of axilla and upper limb lymph nodes
  • C77.9: Secondary and unspecified malignant neoplasm of lymph node, unspecified
  • C78.00: Secondary malignant neoplasm of unspecified lung
  • C79.31: Secondary malignant neoplasm of brain
  • C79.51: Secondary malignant neoplasm of bone
  • Cervical, contralateral internal mammary and contralateral axillary lymph nodes are distant metastases (pM1)
  • Ipsilateral axillary, intramammary, internal mammary and supraclavicular lymph nodes are considered regional nodes, not distant, and are part of pathologic nodal staging of the primary tumor (pN)
  • HER2+ and triple negative (ER- / PR- / HER2-) breast tumors typically recur within 5 years of primary diagnosis (J Cancer Res Clin Oncol 2018 Apr 19 [Epub ahead of print])
  • Basal-like tumors have higher rates of brain, lung and distant nodal metastases than liver and bone (J Clin Oncol 2010;28:3271)
  • ER+ tumors often recur after long periods and have a propensity to first metastasize to bone (Medicine (Baltimore) 2016;95:e2909)
  • Malignant phyllodes tumors and primary sarcomas of the breast have a propensity to metastasize to lungs, bones and liver (Br J Cancer 2004;91:237)
Radiology description
  • Imaging studies are utilized to screen for regional and distant metastases, focusing on organs most frequently involved in breast carcinoma
  • Axillary ultrasound or MRI may be used for preoperative evaluation of regional lymph nodes to determine clinical stage
  • National Comprehensive Cancer Network (NCCN) guidelines version 1.2018 for preoperative workup (NCCN: NCCN Guidelines [Accessed 24 May 2018]):
    • For clinical stage I - IIB: additional studies only if clinical signs or symptoms (i.e. bone scan if bone pain or elevated alkaline phosphatase; abdominal CT or MRI if abnormal liver function tests or abdominal symptoms)
    • For clinical stage IIIA (T3, N1, M0): strongly consider chest, abdominal and pelvic CT with contrast or MRI, bone scan, FDG PET / CT
Prognostic factors
  • ER status and lymph node involvement are significant prognostic factors for late skeletal recurrence (Medicine (Baltimore) 2016;95:e2909)
  • Patients with bone metastases at site of first relapse have better overall survival than patients with visceral metastases at site of first relapse (Breast Cancer Res Treat 2000;59:271)
  • Conversion from negative to positive ER or PR or remaining receptor negative is significantly worse than patients remaining receptor positive (Cancer 2012;118:4929)
  • ER or PR conversion from positive in the primary breast tumor to negative in distant metastases is a poor prognostic indicator (Cancer 2012;118:4929)
Case reports
  • 47 year old woman with breast cancer metastases to the gastrointestinal tract, mimicking hyperplastic polyps (Surg Case Rep 2018;4:23)
  • 51 year old woman with menorrhagia, found to have an undiagnosed invasive ductal carcinoma of the breast, metastatic to the endometrium (Am J Case Rep 2018;19:494)
  • 65 year old woman with lobular breast carcinoma, metastatic to anorectum (BMC Res Notes 2018;11:268)
Microscopic (histologic) description
  • Metastatic tumors often resemble the morphology of the primary tumor
  • Only the stromal component of a malignant phyllodes tumor will metastasize and morphologically resembles a primary sarcoma
  • Receptor status in distant metastases often changes from the original primary tumor receptor status (J Natl Cancer Inst 2018 Jan 5 [Epub ahead of print]):
    • Estrogen receptor (ER):
      • 22.5% positive primary to negative in the metastasis
      • 21.5% negative primary to positive in the metastasis
    • Progesterone receptor (PR):
      • 49.4% positive primary to negative in the metastasis
      • 15.9% negative primary to positive in the metastasis
    • HER2:
      • 21.3% positive primary to negative in the metastasis
      • 9.5% negative primary to positive in the metastasis
Microscopic (histologic) images

Contributed by Emily S. Reisenbichler, M.D.

Poorly differentiated breast carcinoma, metastatic to the liver (H&E and GATA3 immunostain)

Case #125

Breast cancer metastases - to endometrial polyp

Breast cancer metastases - to endometrial polyp
(left to right): ER, PR, GCDFP-15

Breast cancer metastases - to cervix

Positive stains
Differential diagnosis
Board review style question #1
What is the most likely combination of the site of breast carcinoma metastasis, tumor type and timing of metastases from primary diagnosis?

  1. ER+ / PR+ / HER2- metastasis to bone 10 years after primary diagnosis
  2. ER- / PR- / HER2- metastasis to bone 10 years after primary diagnosis
  3. ER+ / PR+ / HER2- metastasis to brain 2 years after primary diagnosis
  4. ER- / PR- / HER2- metastasis to ovary 10 years after primary diagnosis
Board review style answer #1
A. ER+ / PR+ / HER2- metastasis to bone 10 years after primary diagnosis. Hormone receptor+ (estrogen receptor+ / progesterone receptor+) tumors are more likely to metastasize after long periods and the most frequent site of first distant metastases is the bone. Triple negative (estrogen receptor- / progesterone receptor- / HER2-) tumors typically metastasize within 5 years of primary diagnosis.

Comment Here

Reference: Spread and metastases
Back to top
Image 01 Image 02