Breast cancer staging

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor in Chief(s): Soroush Seifirad, M.D.[2] Ammu Susheela

Overview

Breast cancer used to be staged according to the TNM system. Recently, the American Joint Committee on Cancer (AJCC) Staging Manual (8th edition, last updated 1/25/2018) extensively revised their staging system. The 8th edition of the AJCC TNM breast cancer staging system delivers a flexible platform for prognostic classification based on traditional anatomic factors, which may be modified and enhanced with respect to patient biomarkers and other prognostic panel data. Nevertheless, in order to maintain worldwide value, AJCC tumor staging system remained based on classic TNM anatomic factors. Prognosis is closely linked to results of staging, and staging is also used to allocate patients to treatments both in clinical trials and clinical practice.

Staging

• The 8th edition of the AJCC TNM breast cancer staging system delivers a flexible platform for prognostic classification based on traditional anatomic factors, which may be modified and enhanced with respect to patient biomarkers and other prognostic panel data.
• Nevertheless, in order to maintain worldwide value, AJCC tumor staging system remained based on the classic TNM anatomic factors.
• Major changes in the 8th edition of AJCC TNM staging system were discussed below.
• AJCC panel incorporated biologic factors into the staging system as follows:

• Tumor grade
• Proliferation rate
• Estrogen and progesterone receptor expression
• Human epidermal growth factor 2 (HER2) expression
• Gene expression prognostic panels

• Hence components of recent breast cancer staging system are as follows:

• The extent (size) of the tumor (T)
• The spread to nearby lymph nodes (N)
• The spread (metastasis) to distant sites (M)
• Estrogen receptor (ER) presence
• Progesterone receptor (PR) presence
• Her2/neu (HER2) presence
• Histopathologic grade of the cancer (G):
• In certain circumstances, gene expression panels might also be used such as The Oncotype DX® and the MammaPrint® .

Gene expression panels

• Oncotype DX®:

• For small hormone receptor-positive tumors that have not spread to more than 3 lymph nodes
• Also may be used for more advanced tumors
• Might be used for DCIS (ductal carcinoma in situ or stage 0 breast cancer). as well looks at a set of 21 genes in tumor biopsy samples to get a “recurrence score,” which is a number between 0 and 100.
• The score reflects the risk of breast cancer coming back (recurring) in the next 10 years and how likely you will benefit from getting chemo after surgery.
• The lower the score (usually 0-10) the lower the risk of recurrence.
• Benefit from chemotherapy is in doubt in most women with low scores
• An intermediate score (usually 11-25): intermediate risk of recurrence.
• Benefit from chemotherapy is in doubt in most women with intermediate-recurrence scores,
• Nevertheless chemotherapy is believed to be beneficial for women younger than 50 with a higher intermediate score (16-25)
• The possible risks and benefits of chemo should be weighted and discussed prior to decision making.
• A high score (usually 26-100): higher risk of recurrence.Chemotherapy is recommended for women with high scores in order to help lower the chance of cancer *recurrence.
• OncotypeDx is the only multigene panel with level I of evidence, and hence has been incorporated in the AJCC staging system

• MammaPrint®:

• To determine the likelihood of cancer recurrence in a distant part of the body after treatment.
• May be used in any type of breast cancer with stage 1 or 2 that has spread to no more than 3 lymph nodes.
• Hormone and HER2 status are also evaluated in this test. Seventy different genes are examined in this test to determine the 10 years cancer recurrence
• The test results are reported as either “low risk” or “high risk.”
• Unlike OncotypeDx has not been incorporated in the AJCC staging system yet.

TNM Staging

According to the AJCC statement "Content is available for user's personal use. It can not be sold, published or incorporated into any software, product or publication with a written license agreement with ACS." Hence, we may not provide the details of their recent staging system here.

You may find more information for your personal use here.

Breast carcinoma TNM anatomic stage group

• This system is solely recommended for countries with no/limited access to the other mentioned biochemical and genetic tests.
• This system is the classic Tumor(T) Lymph Node(N), Metastasis (M) system.

Prognostic stage groupings

• Patients has been assigned to clinical prognosis stages with respect to the above-mentioned criteria.
• The clinical prognostic stage applies to all patients with breast cancer.
• It is the primary prognostic staging system for patients who receive neoadjuvant treatment or for those who do not receive surgery.
• It is based on clinical T, N, and M; grade; and HER2 and hormone receptor status and does not include genomic profile information.

Approach to determine the prognostic stage groupings of the patients according to the AJCC staging recommendations for breast cancer (8th edition)

Approach to determine the clinical prognostic stage group of the patients according to the AJCC staging recommendations for breast cancer (8th edition). The diagram is the authors' (Soroush Seifirad) own work.

Adopted and modified from AJCC 8th Edition staging system.

Pathologic prognostic stage

• For patients who receive surgical resection as initial treatment,
• Based on:

• Pathologic T, N, and M;
• Pathologic grade;
• HER2
• Hormone receptor status
• and for T1 to T2 N0, ER-positive, HER2-negative disease:

• Genomic testing.  

Summary of stages

In a nutshell

In a nutshell, rather than classic TNM staging system, the following biological factors were incorporated into the prognostic staging system of the eighth edition of the AJCC staging manual:

• Estrogen receptor (ER) and progesterone receptor (PR) expression
• Human epidermal growth factor receptor 2 (HER2)
• Histologic grade
• Recurrence Score (RS): Oncotype DX

In addition to the above-mentioned factors, the AJCC mentioned several other factors that might help to determine the prognosis in patients with breast cancer, although the followings were not formally included in the current staging system:

• Ki-67 :

• Cellular proliferation and tumor balk marker

• Multigene expression assays other than RS:

• Mammaprint, EndoPredict, PAM50 Risk of Recurrence (ROR), and the Breast Cancer Index (level II evidence)

• Risk assessment models:

• Adjuvant! Online
• PREDICT-Plus

• Circulating tumor cells (CTCs):

• Cancer cells that separate from solid tumors and enter the bloodstream
• The cutoff for an unfavorable prognosis is ≥5 cells/7.5 mL

• Disseminated tumor cells (DTCs):

• Disseminated tumor cells in the bone marrow
• Might predict the likelihood of relapse at the time of initial tumor resection
• The relevant cutoff is ≥1 cell.

References

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