Breast Cancer Treatment (PDQ®) 2/4 —Health Professional Version - National Cancer Institute

Breast Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Breast Cancer Treatment (PDQ®)–Health Professional Version

Histopathologic Classification of Breast Cancer

Table 1 describes the histologic classification of breast cancer based on tumor location.[1] Infiltrating or invasive ductal cancer is the most common breast cancer histologic type and comprises 70% to 80% of all cases.

Table 1. Tumor Location and Related Histologic Subtype

Tumor Location	Histologic Subtype
NOS = not otherwise specified.
Carcinoma, NOS
Ductal	Intraductal (in situ)
	Invasive with predominant component
	Invasive, NOS
	Comedo
	Inflammatory
	Medullary with lymphocytic infiltrate
	Mucinous (colloid)
	Papillary
	Scirrhous
	Tubular
	Other
Lobular	Invasive with predominant in situ component
	Invasive [2]
Nipple	Paget disease, NOS
	Paget disease with intraductal carcinoma
	Paget disease with invasive ductal carcinoma
Other	Undifferentiated carcinoma
	Metaplastic

The following tumor subtypes occur in the breast but are not considered typical breast cancers:

• Phyllodes tumor.[3,4]
• Angiosarcoma.
• Primary lymphoma.

References

1. Breast. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 347-76.
2. Yeatman TJ, Cantor AB, Smith TJ, et al.: Tumor biology of infiltrating lobular carcinoma. Implications for management. Ann Surg 222 (4): 549-59; discussion 559-61, 1995. [PUBMED Abstract]
3. Chaney AW, Pollack A, McNeese MD, et al.: Primary treatment of cystosarcoma phyllodes of the breast. Cancer 89 (7): 1502-11, 2000. [PUBMED Abstract]
4. Carter BA, Page DL: Phyllodes tumor of the breast: local recurrence versus metastatic capacity. Hum Pathol 35 (9): 1051-2, 2004. [PUBMED Abstract]

Stage Information for Breast Cancer

In This Section

• TNM Definitions
• AJCC Anatomic and Prognostic Stage Groups
• AJCC Pathological Prognostic Stage Groups

The American Joint Committee on Cancer (AJCC) staging system provides a strategy for grouping patients with respect to prognosis. Therapeutic decisions are formulated in part according to staging categories but also according to other clinical factors such as the following, some of which are included in the determination of stage:

• Tumor size.
• Lymph node status.
• Estrogen-receptor and progesterone-receptor levels in the tumor tissue.
• Human epidermal growth factor receptor 2 (HER2/neu) status in the tumor.
• Tumor grade.
• Menopausal status.
• General health of the patient.

The standards used to define biomarker status are described as follows:

• Estrogen receptor (ER) expression: ER expression is measured primarily by immunohistochemistry (IHC). Any staining of 1% of cells or more is considered positive for ER.[1]
• Progesterone receptor (PR) expression: PR expression is measured primarily by IHC. Any staining of 1% of cells or more is considered positive for PR.
• HER2 expression: HER2 is measured primarily by either IHC to assess expression of the HER2 protein or by in situ hybridization (ISH) to assess gene copy number. The American Society of Clinical Oncology/College of American Pathologists consensus panel has published guidelines for cases when either IHC or ISH testing is equivocal.[2]
  IHC:
  • Negative: 0 or 1+ staining
  • Equivocal: 2+ staining
  • Positive: 3+ staining
  ISH (dual probe):
  • Possible negative results:
    • HER2/chromosome enumeration probe (CEP17) ratio <2.0 AND HER2 copy number <4
  • Possible equivocal results: (requires performing alternative ISH test to confirm equivocal or IHC if not previously performed)
    • HER2/CEP17 ratio <2.0 AND HER2 copy number ≥4 but <6
  • Possible positive results:
    • HER2/CEP17 ratio ≥2.0 by ISH
    • HER2 copy number ≥6 regardless of ratio by ISH
  ISH (single probe):
  • Negative: <4 HER2 copies
  • Equivocal: ≥4 HER2 copies but <6 HER2 copies
  • Positive: ≥6 HER2 copies

TNM Definitions

The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define breast cancer.[3] The grade of the tumor is determined by its morphologic features, such as tubule formation, nuclear pleomorphism, and mitotic count.

Table 2. Definition of Primary Tumor (T) – Clinical and Pathologicala

T Category	T Criteria
DCIS = ductal carcinoma in situ.
aReprinted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
bLobular carcinoma in situ is a benign entity and is removed from TNM staging in the AJCC Cancer Staging Manual, 8th ed.
cRules for Classification - The anatomic TNM system is a method for coding extent of disease. This is done by assigning a category of extent of disease for the tumor (T), regional lymph nodes (N), and distant metastases (M). T, N, and M are assigned by clinical means and by adding surgical findings and pathological information to the clinical information. The documented prognostic impact of postneoadjuvant extent of disease and response to therapy warrant clear definitions of the use of the yp prefix and response to therapy. The use of neoadjuvant therapy does not change the clinical (pretreatment) stage. As per TNM rules, the anatomic component of clinical stage is identified with the prefix c (e.g., cT). In addition, clinical staging can include the use of fine-needle aspiration (FNA) or core-needle biopsy and sentinel lymph node biopsy before neoadjuvant therapy. These are denoted with the postscripts f and sn, respectively. Nodal metastases confirmed by FNA or core-needle biopsy are classified as macrometastases (cN1), regardless of the size of the tumor focus in the final pathological specimen. For example, if, prior to neoadjuvant systemic therapy, a patient with a 1 cm primary has no palpable nodes but has an ultrasound-guided FNA biopsy of an axillary lymph node that is positive, the patient will be categorized as cN1 (f) for clinical (pretreatment) staging and is assigned to Stage IIA. Likewise, if the patient has a positive axillary sentinel node identified before neoadjuvant systemic therapy, the tumor is categorized as cN1 (sn) (Stage IIA). As per TNM rules, in the absence of pathological T evaluation (removal of the primary tumor), which is identified with prefix p (e.g., pT), microscopic evaluation of nodes before neoadjuvant therapy, even by complete removal such as sentinel node biopsy, is still classified as clinical (cN).
TX	Primary tumor cannot be assessed.
T0	No evidence of primary tumor.
Tisb	DCIS.
Tis (Paget)	Paget disease of the nipple NOT associated with invasive carcinoma and/or DCIS in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted.
T1	Tumor ≤20 mm in greatest dimension.
–T1mi	Tumor ≤1 mm in greatest dimension.
–T1a	Tumor >1 mm but ≤5 mm in greatest dimension (round any measurement >1.0–1.9 mm to 2 mm).
–T1b	Tumor >5 mm but ≤10 mm in greatest dimension.
–T1c	Tumor >10 mm but ≤20 mm in greatest dimension.
T2	Tumor >20 mm but ≤50 mm in greatest dimension.
T3	Tumor >50 mm in greatest dimension.
T4	Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4.
–T4a	Extension to the chest wall; invasion or adherence to pectoralis muscle in the absence of invasion of chest wall structures does not qualify as T4.
–T4b	Ulceration and/or ipsilateral macroscopic satellite nodules and/or edema (including peau d'orange) of the skin that does not meet the criteria for inflammatory carcinoma.
–T4c	Both T4a and T4b are present.
–T4d	Inflammatory carcinoma (see Rules for Classificationc).

Table 3. Definition of Regional Lymph Nodes – Clinical (cN)a,b

cN Category	cN Criteria
aReprinted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
b(sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or fine-needle aspiration/core needle biopsy, respectively.
cThe cNX category is used sparingly in cases where regional lymph nodes have previously been surgically removed or where there is no documentation of physical examination of the axilla.
dcN1mi is rarely used but may be appropriate in cases where sentinel node biopsy is performed before tumor resection, most likely to occur in cases treated with neoadjuvant therapy.
cNXc	Regional lymph nodes cannot be assessed (e.g., previously removed).
cN0	No regional lymph node metastases (by imaging or clinical examination).
cN1	Metastases to movable ipsilateral Level I, II axillary lymph nodes(s).
–cN1mid	Micrometastases (approximately 200 cells, >0.2 mm, but ≤2.0 mm).
cN2	Metastases in ipsilateral Level I, II axillary lymph nodes that are clinically fixed or matted;
	or in ipsilateral internal mammary nodes in the absence of axillary lymph node metastases.
–cN2a	Metastases in ipsilateral Level I, II axillary lymph nodes fixed to one another (matted) or to other structures.
–cN2b	Metastases only in ipsilateral internal mammary nodes in the absence of axillary lymph node metastases.
cN3	Metastases in ipsilateral infraclavicular (Level Ill axillary) lymph node(s) with or without Level l, II axillary lymph node involvement; or in ipsilateral internal mammary lymph node(s) with Level l, II axillary lymph node metastases; ormetastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement.
–cN3a	Metastases in ipsilateral infraclavicular lymph node(s).
–cN3b	Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s).
–cN3c	Metastases in ipsilateral supraclavicular lymph node(s).

Table 4. Definition of Regional Lymph Nodes – Pathological (pN)a,b

pN Category	pN Criteria
ITCs = isolated tumor cells; RT-PCR = reverse transcriptase-polymerase chain reaction.
aReprinted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
b(sn) and (f) suffixes should be added to the N category to denote confirmation of metastasis by sentinel node biopsy or fine-needle aspiration/core needle biopsy, respectively, with NO further resection of nodes.
pNX	Regional lymph nodes cannot be assessed (e.g., not removed for pathological study or previously removed).
pN0	No regional lymph node metastasis identified or ITCs only.
–pN0(i+)	ITCs only (malignant cell clusters ≤0.2 mm) in regional lymph node(s).
–pN0(mol+)	Positive molecular findings by RT-PCR; no ITCs detected.
pN1	Micrometastases; or metastases in 1–3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy.
–pN1mi	Micrometastases (~200 cells, >0.2 mm, but ≤2.0 mm).
–pN1a	Metastases in 1–3 axillary lymph nodes, at least one metastasis >2.0 mm.
–pN1b	Metastases in ipsilateral internal mammary sentinel nodes, excluding ITCs.
–pN1c	pN1a and pN1b combined.
pN2	Metastases in 4–9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases.
–pN2a	Metastases in 4–9 axillary lymph nodes (at least 1 tumor deposit >2.0 mm).
–pN2b	Metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary nodes.
pN3	Metastases in ≥10 axillary lymph nodes; or in infraclavicular (Level Ill axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive Level l, II axillary lymph nodes; or in >3 axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes.
–pN3a	Metastases in ≥10 axillary lymph nodes (at least 1 tumor deposit >2.0 mm); ormetastases to the infraclavicular (Level III axillary lymph) nodes.
–pN3b	pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging);
	or pN2a in the presence of pN1b.
–pN3c	Metastases in ipsilateral supraclavicular lymph nodes.

Table 5. Definition of Distant Metastasis (M)a

M Category	M Criteria
aReprinted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
bNote that imaging studies are not required to assign the cM0 category.
M0	No clinical or radiographic evidence of distant metastases.b
cM0(i+)	No clinical or radiographic evidence of distant metastases in the presence of tumor cells or deposits ≤0.2 mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastases.
cM1	Distant metastases detected by clinical and radiographic means.
pM1	Any histologically proven metastases in distant organs; or if in nonregional nodes, metastases >0.2 mm.

Table 6. Definition of Histologic Grade (G)a

G	G Definition
SBR = Scarff-Bloom-Richardson grading system, Nottingham Modification.
aReprinted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
GX	Grade cannot be assessed.
G1	Low combined histologic grade (favorable), SBR score of 3–5 points.
G2	Intermediate combined histologic grade (moderately favorable); SBR score of 6–7 points.
G3	High combined histologic grade (unfavorable); SBR score of 8–9 points.

Table 7. Ductal Carcinoma in situ: Nuclear Gradea

G	G Definition
aReprinted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
GX	Grade cannot be assessed.
G1	Low nuclear grade.
G2	Intermediate nuclear grade.
G3	High nuclear grade.

AJCC Anatomic and Prognostic Stage Groups

There are three stage group tables for invasive cancer:[3]

• Anatomic Stage Group. The Anatomic Stage Group table is used in regions of the world where tumor grading and/or biomarker testing for ER, PR, and HER2 are not routinely available. (Refer to Table 8.)
• Clinical Prognostic Stage Group. The Clinical Prognostic Stage Group table is used for all patients in the United States. Patients who have neoadjuvant therapy as their initial treatment should have the clinical prognostic stage and the observed degree of response to treatment recorded, but these patients are not assigned a pathological prognostic stage. (Refer to Table 9.)
• Pathological Prognostic Stage Group. The Pathological Prognostic Stage Group table is used for all patients in the United States who have surgery as initial treatment and have pathological T and N information reported. (Refer to Table 10.)

In the United States, cancer registries and clinicians must use the Clinical and Pathological Prognostic Stage Group tables for reporting. It is expected that testing is performed for grade, HER2, ER, and PR status and that results are reported for all cases of invasive cancer in the United States.

AJCC Anatomic Stage Groups

Table 8. Definition of Anatomic Stage Groupsa

Stage	TNM
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
Notes:
1. T1 includes T1mi.
2. T0 and T1 tumors with nodal micrometastases (N1mi) are staged as Stage IB.
3. T2, T3, and T4 tumors with nodal micrometastases (N1mi) are staged using the N1 category.
4. M0 includes M0(i+).
5. The designation pM0 is not valid; any M0 is clinical.
6. If a patient presents with M1 disease before receiving neoadjuvant systemic therapy, the stage is Stage IV and remains Stage IV regardless of response to neoadjuvant therapy.
7. Stage designation may be changed if postsurgical imaging studies reveal the presence of distant metastases, provided the studies are performed within 4 months of diagnosis in the absence of disease progression, and provided the patient has not received neoadjuvant therapy.
8. Staging following neoadjuvant therapy is denoted with a yc or ypn prefix to the T and N classification. There is no anatomic stage group assigned if there is a complete pathological response (pCR) to neoadjuvant therapy, for example, ypT0, ypN0, cM0.
0	Tis, N0, M0
IA	T1, N0, M0
IB	T0, N1mi, M0
	T1, N1mi, M0
IIA	T0, N1, M0
	T1, N1, M0
	T2, N0, M0
IIB	T2, N1, M0
	T3, N0, M0
IIIA	T0, N2, M0
	T1, N2, M0
	T2, N2, M0
	T3, N1, M0
	T3, N2, M0
IIIB	T4, N0, M0
	T4, N1, M0
	T4, N2, M0
IIIC	Any T (Tis, T1, T0, T2, T3, T4; N3, M0)
IV	Any T (Tis, T1, T0, T2, T3, T4; Any N = N0, N1mi, N1, N2, N3, M1)

AJCC Prognostic Stage Groups

The Clinical Prognostic Stage is used for clinical classification and staging of patients in the United States with invasive breast cancer. It uses TNM information based on the patient’s history, physical examination, imaging results (not required for clinical staging), and biopsies.

Table 9. Definition of Clinical Prognostic Stage Groupsa

TNM	Grade	HER2 Status	ER Status	PR Status	Stage Group
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
bT1 includes T1mi.
cN1 does not include N1mi. T1, N1mi, M0, and T0, N1mi, M0 cancers are included for prognostic staging with T1, N0, M0 cancers of the same prognostic factor status.
dN1 includes N1mi. T2, T3, and T4 cancers and N1mi are included for prognostic staging with T2, N1; T3, N1; and T4, N1, respectively.
Notes:
1. Because N1mi categorization requires evaluation of the entire node, and cannot be assigned on the basis of an fine-needle aspiration or core biopsy, N1mi can only be used with Clinical Prognostic Staging when clinical staging is based on a resected lymph node in the absence of resection of the primary cancer, such as in the situation where sentinel node biopsy is performed before receiving neoadjuvant chemotherapy or endocrine therapy.
2. For cases with lymph node involvement with no evidence of primary tumor (e.g., T0, N1, etc.) or with breast ductal carcinoma in situ (e.g.,Tis, N1, etc.), the grade, human epidermal growth factor receptor 2 (HER2), estrogen receptor, and progesterone receptor information from the tumor in the lymph node should be used for assigning stage group.
3. For cases where HER2 is determined to be equivocal by in situ hybridization (fluorescence in situ hybridization or chromogenic in situ hybridization) testing under the 2013 American Society of Clinical Oncologists/College of American Pathologists HER2 testing guidelines, the HER2-negative category should be used for staging in the Pathological Prognostic Stage Group table.[4,5]
4. The prognostic value of these Prognostic Stage Groups is based on populations of persons with breast cancer that have been offered and mostly treated with appropriate endocrine and/or systemic chemotherapy (including anti–HER2 therapy).
Tis, N0, M0	Any (refer to Table 6 and Table 7)	Any	Any	Any	0
T1b, N0, M0	G1	Positive	Positive	Positive	IA
				Negative	IA
T0, N1mi, M0			Negative	Positive	IA
				Negative	IA
T1b, N1mi, M0		Negative	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IB
	G2	Positive	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IA
		Negative	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IB
	G3	Positive	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IA
		Negative	Positive	Positive	IA
				Negative	IB
			Negative	Positive	IB
				Negative	IB
T0, N1c, M0; T1b, N1c, M0; T2, N0, M0	G1	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIA
		Negative	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIA
	G2	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIA
		Negative	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIB
	G3	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIA
		Negative	Positive	Positive	IIA
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
T2, N1d, M0; T3, N0, M0	G1	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIB
		Negative	Positive	Positive	IIA
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
	G2	Positive	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIB
		Negative	Positive	Positive	IIA
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIIB
	G3	Positive	Positive	Positive	IB
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
		Negative	Positive	Positive	IIB
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIB
T0, N2, M0; T1b, N2, M0; T2, N2, M0; T3, N1d, M0; T3, N2, M0	G1	Positive	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIA
		Negative	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIB
	G2	Positive	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIA
		Negative	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIB
	G3	Positive	Positive	Positive	IIB
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIA
		Negative	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIC
T4, N0, M0; T4, N1d, M0; T4, N2, M0; Any T, N3, M0	G1	Positive	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIB
		Negative	Positive	Positive	IIIB
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIC
	G2	Positive	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIB
		Negative	Positive	Positive	IIIB
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIC
	G3	Positive	Positive	Positive	IIIB
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIB
		Negative	Positive	Positive	IIIB
				Negative	IIIC
			Negative	Positive	IIIC
				Negative	IIIC
Any T, Any N, M1	Any (refer to Table 6 and Table 7)	Any	Any	Any	IV

AJCC Pathological Prognostic Stage Groups

The Pathological Prognostic Stage applies to patients with invasive breast cancer initially treated with surgery. It includes all information used for clinical staging, surgical findings, and pathological findings following surgery to remove the tumor. Pathological Prognostic Stage is not used for patients treated with neoadjuvant therapy before surgery to remove the tumor.[3]

Table 10. Definition of Pathological Prognostic Stage Groupsa

TNM	Grade	HER2 Status	ER Status	PR Status	Stage Group
T = primary tumor; N = regional lymph node; M = distant metastasis.
aAdapted with permission from AJCC: Breast, revised version. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 4–96.
bT1 includes T1mi.
cN1 does not include N1mi. T1, N1mi, M0 and T0, N1mi, M0 cancers are included for prognostic staging with T1, N0, M0 cancers of the same prognostic factor status.
dN1 includes N1mi. T2, T3, and T4 cancers and N1mi are included for prognostic staging with T2, N1; T3, N1; and T4, N1, respectively.
Notes:
1. For cases with lymph node involvement with no evidence of primary tumor (e.g., T0, N1, etc.) or with breast ductal carcinoma in situ (e.g.,Tis, N1, etc.), the grade, human epidermal growth factor receptor 2 (HER2), estrogen receptor, and progesterone receptor information from the tumor in the lymph node should be used for assigning stage group.
2. For cases where HER2 is determined to be equivocal by in situ hybridization (fluorescence in situ hybridization or chromogenic in situ hybridization) testing under the 2013 American Society of Clinical Oncologists/College of American Pathologists HER2 testing guidelines, the HER2-negative category should be used for staging in the Pathological Prognostic Stage Group table.[4,5]
3. The prognostic value of these Prognostic Stage Groups is based on populations of persons with breast cancer that have been offered and mostly treated with appropriate endocrine and/or systemic chemotherapy (including anti–HER2 therapy).
Tis, N0, M0	Any (refer to Table 6 and Table 7)	Any	Any	Any	0
T1b, N0, M0; T0, N1mi, M0; T1b, N1mi, M0	G1	Positive	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IA
		Negative	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IA
	G2	Positive	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IA
		Negative	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IB
	G3	Positive	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IA
		Negative	Positive	Positive	IA
				Negative	IA
			Negative	Positive	IA
				Negative	IB
T0, N1c , M0; T1b, N1c, M0; T2, N0, M0	G1	Positive	Positive	Positive	IA
				Negative	IB
			Negative	Positive	IB
				Negative	IIA
		Negative	Positive	Positive	IA
				Negative	IB
			Negative	Positive	IB
				Negative	IIA
	G2	Positive	Positive	Positive	IA
				Negative	IB
			Negative	Positive	IB
				Negative	IIA
		Negative	Positive	Positive	IA
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIA
	G3	Positive	Positive	Positive	IA
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIA
		Negative	Positive	Positive	IB
				Negative	IIA
			Negative	Positive	IIA
				Negative	IIA
T2, N1c, M0; T3, N0, M0	G1	Positive	Positive	Positive	IA
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
		Negative	Positive	Positive	IA
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
	G2	Positive	Positive	Positive	IB
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
		Negative	Positive	Positive	IB
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
	G3	Positive	Positive	Positive	IB
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIB
		Negative	Positive	Positive	IIA
				Negative	IIB
			Negative	Positive	IIB
				Negative	IIIA
T0, N2, M0; T1b, N2, M0; T2, N2, M0, T3, N1d, M0; T3, N2, M0	G1	Positive	Positive	Positive	IB
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIA
		Negative	Positive	Positive	IB
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIA
	G2	Positive	Positive	Positive	IB
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIA
		Negative	Positive	Positive	IB
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIB
	G3	Positive	Positive	Positive	IIA
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIA
		Negative	Positive	Positive	IIB
				Negative	IIIA
			Negative	Positive	IIIA
				Negative	IIIC
T4, N0, M0; T4, N1d, M0; T4, N2, M0; Any T, N3, M0	G1	Positive	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIB
		Negative	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIB
	G2	Positive	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIB
		Negative	Positive	Positive	IIIA
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIC
	G3	Positive	Positive	Positive	IIIB
				Negative	IIIB
			Negative	Positive	IIIB
				Negative	IIIB
		Negative	Positive	Positive	IIIB
				Negative	IIIC
			Negative	Positive	IIIC
				Negative	IIIC
Any T, Any N, M1	Any (refer to Table 6 and Table 7)	Any	Any	Any	IV

References

1. Barnes DM, Harris WH, Smith P, et al.: Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer 74 (9): 1445-51, 1996. [PUBMED Abstract]
2. Wolff AC, Hammond MEH, Allison KH, et al.: Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol 36 (20): 2105-2122, 2018. [PUBMED Abstract]
3. Breast. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 589–628.
4. Wolff AC, Hammond ME, Hicks DG, et al.: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 31 (31): 3997-4013, 2013. [PUBMED Abstract]
5. Wolff AC, Hammond ME, Hicks DG, et al.: Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 138 (2): 241-56, 2014. [PUBMED Abstract]