Updated Interpretation of AJCC Breast Invasive Cancer N Staging, 8th Edition, 2018

The word cancer comes from Hippocrates, and in the past, people were afraid of cancer, but with increasing health awareness, early detection of cancer, and advances in treatment technology, the survival rate and quality of life of cancer patients have greatly improved, and people no longer talk about cancer.

What is AJCC?

What is AJCC staging?

What is AJCC staging?

The AJCC stands for American Joint Committee on Cancer, a joint initiative of the American College of Surgeons, the American College of Radiology, the College of American Pathologists, the American College of Physicians, the American Cancer Society, and the National Cancer Institute. The AJCC cancer staging is the common language for cancer clinical and research worldwide, as this association and the International Union Against Cancer (UICC) respect each other and perfect the staging system based on anatomical primary tumor (T), regional lymph node (N), and distant metastasis (M). This time, after 7 years, the AJCC breast cancer staging system is updated again, which is of great significance to the diagnosis and treatment of breast cancer. Today we will focus on N staging in the latest 8th edition of staging.

Specifics of N-staging in the 8th edition of AJCC Breast Cancer Staging

The changes in N staging in the 8th edition of breast cancer are minor, but the pathologic criteria for lymph node metastasis are clearer. Unlike T-staging, N-staging in invasive breast cancer includes both clinical N-staging (cN) and pathologic N-staging (pN). The so-called pN is a unique aspect of N staging, in which the pathologist examines the lymph nodes and classifies the number of metastatic lymph nodes and the size of metastatic foci in the lymph nodes, and even the number of metastatic tumor cells.

First, let’s look at the specifics of AJCC 8th edition breast cancer N staging:

Clinical N staging (cN)

cNX

Regional lymph nodes not resected or previously resected

cN0 No regional lymph node metastasis
cN1 Ipsilateral Ⅰ and Ⅱ level axillary lymph node metastasis with movable lymph nodes
cN1mi micro-metastases
cN2 Ipsilateral Ⅰ or Ⅱ level axillary lymph node metastasis, fixed or fused; or clinical signs of ipsilateral internal breast lymph node metastasis without clinical signs of axillary lymph node metastasis
cN2a Ipsilateral Ⅰ or Ⅱ level axillary lymph node metastasis with fixation or fusion of lymph nodes with each other or with other structures
cN2b

Clinical signs of ipsilateral internal breast lymph node metastasis only, without clinical signs of axillary lymph node metastasis at the level of I and II

cN3

Ipsilateral subclavian lymph node metastasis with or without Ⅰ or Ⅱ level axillary lymph node metastasis; or clinical signs of ipsilateral internal breast lymph node metastasis with axillary lymph node metastasis; or ipsilateral supraclavicular lymph node metastasis with or without axillary or internal breast lymph node metastasis

cN3a  Ipsilateral subclavian lymph node metastasis
cN3b Ipsilateral internal mammary lymph node and axillary lymph node metastases
cN3c Ipsilateral supraclavicular lymph node metastasis

Pathology N stage (pN)

) detected by sentinel lymph node biopsy

pNX Regional lymph nodes not resected or previously resected
pN0 No regional lymph node metastasis or only isolated tumor cells
pN0(i+)

Regional lymph nodes with isolated tumor cells only

pN0(mol+) Reverse transcriptase-polymerase chain reaction (RT-PCR) shows positive at the molecular level; no isolated tumor cells identified
pN1

Micro-metastases; or 1-3 ipsilateral axillary lymph node metastases, and/or microscopic metastases in internal breast lymph nodes detected by anterior lymph node biopsy, but no clinical signs

pN1mi micro-metastases
pN1a 1-3 axillary lymph node metastases with at least 1 metastasis >2 mm
pN1b Microscopic metastasis to internal breast lymph nodes (excluding isolated tumor cells
pN1c pN1a + pN1b
pN2 4-9 axillary lymph node metastases; or no axillary lymph node metastases, but internal breast lymph node metastases (with clinical signs)
pN2a 4-9 axillary lymph node metastases with at least 1 metastasis >2 m
pN2b Ipsilateral internal breast lymph node metastasis with clinical signs of metastasis, but no axillary lymph node metastasis
pN3

≥10 axillary lymph node metastases; or subclavian lymph node metastases; or ipsilateral internal breast lymph node metastases (with clinical signs) with ≥1 axillary lymph node metastases; or >3 axillary lymph node metastases with anterior lymph node biopsy revealing internal breast lymph node micrometastases or macrometastases without clinical signs; or ipsilateral supraclavicular lymph node metastases

pN3a ≥10 ipsilateral axillary lymph node metastases (at least 1 metastasis >2 mm), or subclavian lymph node metastases
pN3b cN2b (clinical sign of internal breast lymph node metastasis) with pN1a or pN2a, or pN1b with pN2a
pN3c Ipsilateral supraclavicular lymph node metastasis

Note: With clinical signs – lymph node metastasis on clinical examination or imaging (excluding lymphatic special angiography); high suspicion of metastasis; or needle aspiration cytology presumptive for the presence of lymph node macro-metastasis; needle aspiration cytology rather than excisional biopsy confirmed metastasis. No clinical signs – no metastases detected on clinical examination or imaging analysis (excluding lymphatic special angiography).

Since it is the staging of the lymph nodes, the most important concern for people with cancer is the presence or absence of metastases in the lymph nodes. We can see that more lymph node metastases later in the staging means more advanced N staging, which means a relatively poor prognosis. But what do macro-metastases, micrometastases, and isolated tumor cells in the lymph nodes mean in staging?

  • Macrometastasis is a tumor cell metastasis larger than 2 mm in a lymph node pathology section.
  • Micro-metastasis is defined as a tumor cell metastasis of 0.2-2 mm in a lymph node pathology section, or a single pathology section with more than 200 tumor cells.
  • Isolated tumor cells were defined as single tumor cells or clusters of tumor cells found by lymph node pathology or immunohistochemistry, and the size of the lesion did not exceed 0.2 mm; for scattered tumors, the number of tumor cells in a single pathology section per lymph node did not exceed 200. Lymph nodes containing only isolated tumor cells cannot be counted as metastatic lymph nodes.

What are the major changes in N staging in the 8th edition compared with the 7th edition?

The 8th edition N staging includes a single largest contiguous metastatic lymph node in the pN, and the total area of multiple metastases within a lymph node does not affect the pN staging. Pathologic classification requires removal of at least the axillary lymph nodes, which usually include at least 6 lymph nodes. If there were no metastases in the lymph nodes, but the total number of lymph nodes was insufficient, the classification was pN0.

In addition, pN0(i-) and pN0(mol-) were removed from the pN0 catalog compared with version 7. And cN1mi was added to cN, mainly for patients before neoadjuvant therapy.

Is it necessary to perform intraoperative pathological evaluation of the sentinel lymph nodes?

The so-called sentinel lymph nodes are the first lymph nodes through which the tumor must pass to develop lymph node metastasis. If we compare the axillary lymph nodes of the breast to a “military camp,” then the sentinel lymph nodes are the “sentinels. If the “sentinel” is invaded by tumor, then the “barracks” may also be invaded; and if the “sentinel” is not invaded, then the “barracks The “barracks” can be considered not to have been invaded.

Intraoperative pathologic evaluation of the anterior sentinel lymph node is the intraoperative determination of metastases in the lymph node by rapid pathologic testing techniques designed to detect metastatic lesions in the lymph node and thus perform axillary lymph node dissection to avoid secondary surgery. The necessity of intraoperative pathologic evaluation of the anterior lymph nodes is currently controversial. Studies have shown that breast-conserving patients with clinical stage T1-2, N0, and M0 and one or two anterior lymph node metastases do not have increased overall or tumor-free survival rates because of anterior lymph node metastases, nor do they have decreased recurrent metastasis rates, so intraoperative assessment of anterior lymph node status is no longer performed in some pathology departments.

Breast cancer has long been a highly prevalent tumor in women, posing a serious threat to the lives of women worldwide, and the update of the AJCC is an important safeguard to ensure that breast cancer patients receive standardized diagnosis and treatment. We believe that with the development of science, technology and treatment protocols, the day when cancer will be conquered is not far away.