Breast Cancer Staging

Dr Kwan Wing Hong
M.B., B.S. (HK), F.R.C.R., F.H.K.C.R., F.H.K.A.M. (Rad)

The purpose of staging is to separate breast cancer patients into different prognostic subgroups. Based on past clinical experience, doctor can tell patients at different disease stages their approximate rate of relapse and probability of cure. It also helps the doctor to choose the best treatment method for individual patients as well as comparing his own treatment result with others.

The most commonly used staging system for breast cancer is the UICC/AJC Staging System. The updated sixth edition is published in 2002. It can either be a clinical or pathologic staging. Clinical staging is based on the information on physical examination while pathologic staging rely on the final pathology of the surgical specimen. The pathologic staging is used to guide adjuvant treatment and is more predictive for the outcome.

UICC Staging System separates patients into different groups by virtue of three important criteria; the T, N and M category. T staging depends on the size of the invasive component of the tumour as well as whether there is invasion of adjacent tissue. T1 to T3 are mobile tumour separated by their sizes (T1 2cm, T2 >2cm but 5cm, T3 >5cm) while T4 means tumour invasion of skin (T4a), underlying chest wall (T4b) or both (T4c). T4d referred to inflammatory breast cancer mimicking a rapid onset breast abscess. The entire breast is swollen and tender with skin thickening. In about half of these cases, the malignant cells grow so rapidly and invade so extensively that no mass is palpable inside the breast.

N Stage refers to the status of the regional lymphatic nodal basins. Majority of lymphatic drainage of the breast goes to the axilla on the same side while minority goes to the internal mammary chain which is situated about 2cm deep to the edge of the sternum. Cancer cells can spread further from the axillary and internal mammary chain to secondary stations in the infraclavicular and supraclavicular region. Pathologic N stage is much more important than the clinical N stage. Clinically enlarged lymph node may be reactive and do not contain cancer cells when removed and examined under the microscope. On the contrary, normal sized lymph node may already harbour tiny metastatic focus. Innovative pathologic technique could identify metastasis down to isolated tumour cells level using immunohistochemical staining or molecular technology. It is for this reason that breast cancer surgeries always incorporate removal of drainage lymph nodes for proper staging and prognosis. The N stage is categorized into different groups by the total number of involved nodes as well as the region of involved nodes. The larger the number of involved nodes and the further away the involved nodal region from the breast, the higher will be the N stage.

M stage refers to whether the disease is localized or disseminated. Results of clinical examination and various imaging techniques are used to exclude distant spread. In the absence of suspicious clinical sign and symptom as well as abnormal baseline blood results of liver and renal function tests, it is not mandatory to order extensive diagnostic imaging to rule out metastatic spread. Lung, bone and liver are the commonest sites of dissemination.

Primary Tumor: (T)

T_x Primary tumour cannot be assessed

T₀ No evidence of primary tumour

T_is Carcinoma in situ

T_is(DCIS) Ductal carcinoma in situ

T_is(LCIS) Lobular carcinoma in situ

T_{is(Piget’s)} Paget’s disease of the nipple with no tumour

Note: Paget’s disease associated with a tumour is classified according to the size of the tumour

T₁ Tumour 2 cm or less in greatest dimension

T_1mic Microinvasion 0.1 cm or less in greatest dimension

T_1a Tumour more than 0.1 cm but not more than 0.5 cm in greatest dimension

T_1b Tumour more than 0.5 cm but not more than 1 cm in greatest dimension

T_1c Tumour more than 1 cm but not more than 2 cm in greatest dimension

T₂ Tumour more than 2 cm but not more than 5 cm in greatest dimension

T₃ Tumour more than 5 cm in greatest dimension

T₄ Tumour of any size with direct extension to:

1. a)chest wall or
2. b)skin, only as described below

T_4a Extension to chest wall, not including pectoralis muscle

T_4b Edema (including peau d’orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast

T_4c Both T_4a and T_4b

T_4d Inflammatory carcinoma

Regional Lymph Nodes (N)

N_x Regional lymph nodes cannot be assessed (e.g. previously removed)

N₀ No regional lymph node metastasis

N₁ Metastasis in movable ipsilateral axillary lymph node(s)

N₂ Metastasis in ipsilateral axillary lymph nodes fixed or matted, or in clinically apparent⁽¹⁾ ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis

N_2a Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structure

N_2b Metastasis only in clinically apparent⁽¹⁾ ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis

N₃ Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent⁽¹⁾ ipsilateral internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement

N_3a Metastasis in ipsilateral infraclavicular lymph node(s) and axillary lymph node(s)

N_3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph nodes

N_3c Metastasis in ipsilateral supraclavicular lymph node(s)

Pathologic Regional Lymph Nodes (pN)⁽²⁾

pN_x Regional lymph nodes cannot be assessed (e.g., previously removed, or not removed for pathologic study)

pN₀ No regional lymph node metastasis histologically, no additional examination for isolated tumor cells (ITC)⁽³⁾

pN_0(i-) No regional lymph node metastasis histologically, negative IHC

pN_0(i+) No regional lymph node metastasis histologically, positive IHC, no IHC cluster greater than 0.2 mm

pN_0(mol-) No regional lymph node metastasis histologically, negative molecular findings (RT-PCR)⁽⁴⁾

pN_0(mol+) No regional lymph node metastasis histologically, positive molecular findings (RT-PCR)⁽⁴⁾

pN₁ Metastasis in 1 to 3 axillary lymph nodes, and/or in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent⁽⁵⁾

pN_1mi Micrometastasis (greater than 0.2 mm, none greater than 2.0 mm)

pN_1a Metastasis in 1 to 3 axillary lymph nodes

pN_1b Metastasis in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent⁽⁵⁾

pN_1c Metastasis in 1 to 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent^(5,6)

pN₂ Metastasis in 4 to 9 axillary lymph nodes, or in clinically apparent⁽¹⁾ internal mammary lymph nodes in the absence of axillary lymph node metastasis

pN_2a Metastasis in 4 to 9 axillary lymph nodes (at least one tumour deposit greater than 2.0 mm)

pN_2b Metastasis in clinically apparent⁽¹⁾ internal mammary lymph nodes in the absence of axillary lymph node metastasis

pN₃ Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in clinically apparent⁽¹⁾ ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes with clinically negative microscopic metastasis in internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes

pN_3a Metastasis in 10 or more axillary lymph nodes (at least one tumour deposit greater than 2.0 mm), or metastasis to the infraclavicular lymph nodes

pN_3b Metastasis in clinically apparent⁽¹⁾ ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent⁽⁵⁾

pN_3c Metastasis in ipsilateral supraclavicular lymph nodes

Distant Metastasis (M)

M_x Distant metastasis cannot be assessed

M₀ No distant metastasis

M₁ Distant metastasis

Stage Grouping

0 T_is N₀ M₀

I T₁⁽⁷⁾ N₀ M₀

IIA T₀ N₁ M₀

T₁⁽⁷⁾ N₁ M₀

T₂ N₀ M₀

IIB T₂ N₁ M₀

T₃ N₀ M₀

IIIA T₀ N₂ M₀

T₁⁽⁷⁾ N₂ M₀

T₂ N₂ M₀

T₃ N₁ M₀

T₃ N₂ M₀

IIIB T₄ N₀ M₀

T₄ N₁ M₀

T₄ N₂ M₀

IIIC Any T N₃ M₀

IV Any T Any N M₁

Notes:

(1) Clinically apparent is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination

(2) Classification is based on axillary lymph node dissection with or without sentinel lymph node dissection. Classification based solely on sentinel lymph node dissection without subsequent axillary lymph node dissection is designated (sn) for “sentinel node,” e.g., pN_0(i+)(sn)

(3) Isolated tumour cells (ITC) are defined as single tumour cells or small cell clusters not greater than 0.2 mm, usually detected only by immunohistochemical (IHC) or molecular methods but which may be verified on H&E stains. ITCs do not usually show evidence of metastatic activity (e.g., proliferation or stromal reaction)

(4) PT-PCR: reverse transcriptase/polymerase chain reaction.

(5) Not clinically apparent is defined as not detected by imaging studies (excluding lymphoscintigragphy) or by clinical examination.

(6) If associated with greater than 3 positive axillary lymph nodes, the internal mammary nodes are classified as pN_3b to reflect increased tumour burden

(7) T₁ includes T_1mic