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NCI/PDQ® Health professionals: Breast Cancer Treatment (PDQ®)

National Cancer Institute
Last Modified: January 4, 2013

TABLE OF CONTENTS


General Information About Breast Cancer

Back Up

This summary discusses only primary epithelial breast cancers. Rarely, the breast may be involved by other tumors such as lymphomas, sarcomas, or melanomas. (Refer to the PDQ® summaries on Adult Hodgkin Lymphoma Treatment, Adult Soft Tissue Sarcoma Treatment, and Melanoma Treatment for more information.)


Incidence and Mortality

Estimated new cases and deaths from breast cancer (women only) in the United States in 2012: 1

  • New cases: 226,870.
  • Deaths: 39,510.


Genetic Characteristics and Risk Factors

Several well-established factors have been associated with an increased risk of breast cancer, including family history, nulliparity, early menarche, advanced age, and a personal history of breast cancer (in situ or invasive).

Age-specific risk estimates are available to help counsel and design screening strategies for women with a family history of breast cancer. 2 3 Of all women with breast cancer, 5% to 10% may have a germ-line mutation of the genes BRCA1 and BRCA2. 4 Specific mutations of BRCA1 and BRCA2 are more common in women of Jewish ancestry. 5 The estimated lifetime risk of developing breast cancer for women with BRCA1 and BRCA2 mutations is 40% to 85%. Carriers with a history of breast cancer have an increased risk of contralateral disease that may be as great as 5% per year. 6 Ma le carriers of BRCA2 mutations are also at increased risk for breast cancer. 7

Mutations in either the BRCA1 or BRCA2 gene also confer an increased risk of ovarian cancer. 7 8 9 In addition, mutation carriers may be at increased risk of other primary cancers. 7 9 Genetic testing is available to detect mutations in members of high-risk families. 10 11 12 13 14 Such individuals should first be referred for counseling. 15 (Refer to the PDQ® summaries on Genetics of Breast and Ovarian Cancer; Breast Cancer Prevention; and Breast Cancer Screening for more information.)


Screening

Clinical trials have established that screening with mammography, with or without clinical breast examination, may decrease breast cancer mortality. (Refer to the PDQ® summary on Breast Cancer Screening for more information.)


Patient Evaluation

Patient management following initial suspicion of breast cancer generally includes confirmation of the diagnosis, evaluation of stage of disease, and selection of therapy. At the time the tumor tissue is surgically removed, estrogen receptor (ER) and progesterone receptor (PR) status should be determined.


Prognostic and Predictive Factors

Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. Prognosis and selection of therapy may be influenced by the following clinical and pathology features (based on conventional histology and immunohistochemistry): 16

  • The age and menopausal status of the patient.
  • The stage of the disease.
  • The histologic and nuclear grade of the primary tumor.
  • The ER and PR status of the tumor.
  • Human epidermal growth factor type 2 receptor (HER2/neu) overexpression.
  • Proliferative capacity of the tumor (e.g., Ki67).

Molecular profiling has led to classification of breast cancer into the following five distinct subtypes: 17 18

  • Basal-like.
  • HER2+.
  • Normal.
  • Luminal A.
  • Luminal B.

The use of molecular profiling in breast cancer includes the following: 17 18

  • ER and PR status testing.
  • HER2/neu receptor status testing.
  • Gene profile testing by microarray assay or reverse transcription-polymerase chain reaction (e.g., MammaPrint, Oncotype DX).

Although certain rare inherited mutations, such as those of BRCA1 and BRCA2, predispose women to develop breast cancer, prognostic data on BRCA1/BRCA2 mutation carriers who have developed breast cancer are conflicting; these women are at greater risk of developing contralateral breast cancer. Since criteria for menopausal status vary widely, some studies have substituted age older than 50 years as a surrogate for the postmenopausal state. Breast cancer is classified into a variety of histologic types, some of which have prognostic importance. For example, favorable histologic types include mucinous, medullary, and tubular carcinoma. 19 20 21


Contralateral Disease

Pathologically, breast cancer can be a multicentric and bilateral disease. Bilateral disease is somewhat more common in patients with infiltrating lobular carcinoma. Patients who have breast cancer should have bilateral mammography at the time of diagnosis to rule out synchronous disease. The role of magnetic resonance imaging (MRI) in screening and follow-up continues to evolve. Having demonstrated an increased detection rate of mammographically occult disease, the selective use of MRI for additional screening is being used with increased frequency despite the absence of randomized, controlled data. Because only 25% of MRI-positive findings represent malignancy, pathologic confirmation prior to treatment action is recommended. Whether this increased detection rate will translate into improved treatment outcome is unknown. 22 23 24 When BRCA1/BRCA2 mutation carriers were diagnosed at a young age, the risk of a contralateral breast cancer reached nearly 50% in the ensuing 25 years. 25 26

Patients should continue to have regular breast physical examinations and mammography to detect either recurrence in the ipsilateral breast in those patients treated with breast-conserving surgery or a second primary cancer in the contralateral breast. 27 The risk of a primary breast cancer in the contralateral breast is approximately 1% per year. 28 29 Patient age younger than 55 years at the time of diagnosis or lobular tumor histology appear to increase this risk to 1.5%. 30 The development of a contralateral breast cancer is associated with an increased risk of distant recurrence. 31 32


Hormone Replacement Therapy

The use of hormone replacement therapy (HRT) poses a dilemma for the rising numbers of breast cancer survivors, many of whom enter menopause prematurely as a result of therapy. HRT has generally not been used for women with a history of breast cancer because estrogen is a growth factor for most breast cancer cells in the laboratory; however, empiric data on the safety of HRT after breast cancer are limited. 33 34

Two randomized trials (including Regional Oncologic Center-Hormonal Replacement Therapy After Breast Cancer--Is It Safe [ROC-HABITS]) comparing HRT with no hormonal supplementation have been reported. 35 36 The first trial included 345 evaluable breast cancer patients with menopausal symptoms and was terminated early because of an increased incidence of recurrences and new primaries in the HRT group (hazard ratio [HR], 3.5; 95% confidence interval [CI], 1.57.4). 35[Level of evidence: 1iiDii] In total, 26 women in the HRT group and 7 in the non-HRT group developed recurrences or new primaries. This study, however, was not double blinded, and it is possible that patients on HRT were monitored more closely. Because of the results of the first trial, the second trial, which was conducted under a joint steering committee with the first, closed prematurely after the enrollment of 378 patients. 36 With a median follow-up of 4.1 years, there were 11 recurrences in the hormone replacement group and 13 recurrences in the patients assigned to no hormone replacement (HR, 0.82; 95% CI, 0.351.9). 36[Level of evidence: 1iiDii] The trials differed in several ways; 37 however, until further data become available, decisions concerning the use of HRT in patients with breast cancer will have to be based on the results of these studies and on inferences from the impact of HRT use on breast cancer risk in other settings. 37 A comprehensive intervention, including education, counseling, and nonhormonal drug therapy, has been shown to reduce menopausal symptoms and to improve sexual functioning in breast cancer survivors. 38[Level of evidence: 1iiC] (Refer to the PDQ® summaries on Fever, Sweats, and Hot Flashes and Sexuality and Reproductive Issues for more information.)


Breast Reconstruction

For patients who opt for a total mastectomy, reconstructive surgery may be used at the time of the mastectomy (immediate reconstruction) or at some subsequent time (delayed reconstruction). 39 40 41 42 Breast contour can be restored by the submuscular insertion of an artificial implant (saline-filled) or a rectus muscle or other flap. If a saline implant is used, a tissue expander can be inserted beneath the pectoral muscle. Saline is injected into the expander to stretch the tissues for a period of weeks or months until the desired volume is obtained. The tissue expander is replaced by a permanent implant. (Visit the FDA's Web site for more information on breast implants.) Rectus muscle flaps require a considerably more complicated and prolonged operative procedure, and blood transfusions may be required.

Following breast reconstruction, radiation therapy can be delivered to the chest wall and regional nodes either in the adjuvant setting or if local disease recurs. Radiation therapy following reconstruction with a breast prosthesis may affect cosmesis, and the incidence of capsular fibrosis, pain, or the need for implant removal may be increased. 43


Follow-up

Evidence from randomized trials indicates that periodic follow-up with bone scans, liver sonography, chest x-rays, and blood tests of liver function does not improve survival or quality of life when compared to routine physical examinations. 44 45 46 Even when these tests permit earlier detection of recurrent disease, patient survival is unaffected. 45 Based on these data, some investigators recommend that acceptable follow-up be limited to physical examination and annual mammography for asymptomatic patients who complete treatment for stage I to stage III breast cancer. The frequency of follow-up and the appropriateness of screening tests after the completion of primary treatment for stage I to breast cancer remain controversial.


Related Summaries

Other PDQ® summaries containing information related to breast cancer include the following:

References:

  1. American Cancer Society.: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012. Available online [PUBMED Abstract]
  2. Claus EB, Risch N, Thompson WD: Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer 73 (3): 643-51, 1994. [PUBMED Abstract]
  3. Gail MH, Brinton LA, Byar DP, et al.: Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81 (24): 1879-86, 1989. [PUBMED Abstract]
  4. Blackwood MA, Weber BL: BRCA1 and BRCA2: from molecular genetics to clinical medicine. J Clin Oncol 16 (5): 1969-77, 1998. [PUBMED Abstract]
  5. Offit K, Gilewski T, McGuire P, et al.: Germline BRCA1 185delAG mutations in Jewish women with breast cancer. Lancet 347 (9016): 1643-5, 1996. [PUBMED Abstract]
  6. Frank TS, Manley SA, Olopade OI, et al.: Sequence analysis of BRCA1 and BRCA2: correlation of mutations with family history and ovarian cancer risk. J Clin Oncol 16 (7): 2417-25, 1998. [PUBMED Abstract]
  7. Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J Natl Cancer Inst 91 (15): 1310-6, 1999. [PUBMED Abstract]
  8. Miki Y, Swensen J, Shattuck-Eidens D, et al.: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266 (5182): 66-71, 1994. [PUBMED Abstract]
  9. Ford D, Easton DF, Bishop DT, et al.: Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 343 (8899): 692-5, 1994. [PUBMED Abstract]
  10. Biesecker BB, Boehnke M, Calzone K, et al.: Genetic counseling for families with inherited susceptibility to breast and ovarian cancer. JAMA 269 (15): 1970-4, 1993. [PUBMED Abstract]
  11. Hall JM, Lee MK, Newman B, et al.: Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250 (4988): 1684-9, 1990. [PUBMED Abstract]
  12. Easton DF, Bishop DT, Ford D, et al.: Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet 52 (4): 678-701, 1993. [PUBMED Abstract]
  13. Berry DA, Parmigiani G, Sanchez J, et al.: Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history. J Natl Cancer Inst 89 (3): 227-38, 1997. [PUBMED Abstract]
  14. Hoskins KF, Stopfer JE, Calzone KA, et al.: Assessment and counseling for women with a family history of breast cancer. A guide for clinicians. JAMA 273 (7): 577-85, 1995. [PUBMED Abstract]
  15. Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility, Adopted on February 20, 1996. J Clin Oncol 14 (5): 1730-6; discussion 1737-40, 1996. [PUBMED Abstract]
  16. Simpson JF, Gray R, Dressler LG, et al.: Prognostic value of histologic grade and proliferative activity in axillary node-positive breast cancer: results from the Eastern Cooperative Oncology Group Companion Study, EST 4189. J Clin Oncol 18 (10): 2059-69, 2000. [PUBMED Abstract]
  17. Sírlie T, Perou CM, Tibshirani R, et al.: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98 (19): 10869-74, 2001. [PUBMED Abstract]
  18. Perou CM, Sírlie T, Eisen MB, et al.: Molecular portraits of human breast tumours. Nature 406 (6797): 747-52, 2000. [PUBMED Abstract]
  19. Rosen PP, Groshen S, Kinne DW: Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study. J Clin Oncol 9 (9): 1650-61, 1991. [PUBMED Abstract]
  20. Diab SG, Clark GM, Osborne CK, et al.: Tumor characteristics and clinical outcome of tubular and mucinous breast carcinomas. J Clin Oncol 17 (5): 1442-8, 1999. [PUBMED Abstract]
  21. Rakha EA, Lee AH, Evans AJ, et al.: Tubular carcinoma of the breast: further evidence to support its excellent prognosis. J Clin Oncol 28 (1): 99-104, 2010. [PUBMED Abstract]
  22. Lehman CD, Gatsonis C, Kuhl CK, et al.: MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 356 (13): 1295-303, 2007. [PUBMED Abstract]
  23. Solin LJ, Orel SG, Hwang WT, et al.: Relationship of breast magnetic resonance imaging to outcome after breast-conservation treatment with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. J Clin Oncol 26 (3): 386-91, 2008. [PUBMED Abstract]
  24. Morrow M: Magnetic resonance imaging in the breast cancer patient: curb your enthusiasm. J Clin Oncol 26 (3): 352-3, 2008. [PUBMED Abstract]
  25. Graeser MK, Engel C, Rhiem K, et al.: Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27 (35): 5887-92, 2009. [PUBMED Abstract]
  26. Garber JE, Golshan M: Contralateral breast cancer in BRCA1/BRCA2 mutation carriers: the story of the other side. J Clin Oncol 27 (35): 5862-4, 2009. [PUBMED Abstract]
  27. Orel SG, Troupin RH, Patterson EA, et al.: Breast cancer recurrence after lumpectomy and irradiation: role of mammography in detection. Radiology 183 (1): 201-6, 1992. [PUBMED Abstract]
  28. Rosen PP, Groshen S, Kinne DW, et al.: Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up. J Clin Oncol 11 (11): 2090-100, 1993. [PUBMED Abstract]
  29. Gustafsson A, Tartter PI, Brower ST, et al.: Prognosis of patients with bilateral carcinoma of the breast. J Am Coll Surg 178 (2): 111-6, 1994. [PUBMED Abstract]
  30. Broít P, de la Rochefordiíre A, Scholl SM, et al.: Contralateral breast cancer: annual incidence and risk parameters. J Clin Oncol 13 (7): 1578-83, 1995. [PUBMED Abstract]
  31. Healey EA, Cook EF, Orav EJ, et al.: Contralateral breast cancer: clinical characteristics and impact on prognosis. J Clin Oncol 11 (8): 1545-52, 1993. [PUBMED Abstract]
  32. Heron DE, Komarnicky LT, Hyslop T, et al.: Bilateral breast carcinoma: risk factors and outcomes for patients with synchronous and metachronous disease. Cancer 88 (12): 2739-50, 2000. [PUBMED Abstract]
  33. Cobleigh MA, Berris RF, Bush T, et al.: Estrogen replacement therapy in breast cancer survivors. A time for change. Breast Cancer Committees of the Eastern Cooperative Oncology Group. JAMA 272 (7): 540-5, 1994. [PUBMED Abstract]
  34. Roy JA, Sawka CA, Pritchard KI: Hormone replacement therapy in women with breast cancer. Do the risks outweigh the benefits? J Clin Oncol 14 (3): 997-1006, 1996. [PUBMED Abstract]
  35. Holmberg L, Anderson H; HABITS steering and data monitoring committees.: HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet 363 (9407): 453-5, 2004. [PUBMED Abstract]
  36. von Schoultz E, Rutqvist LE; Stockholm Breast Cancer Study Group.: Menopausal hormone therapy after breast cancer: the Stockholm randomized trial. J Natl Cancer Inst 97 (7): 533-5, 2005. [PUBMED Abstract]
  37. Chlebowski RT, Anderson GL: Progestins and recurrence in breast cancer survivors. J Natl Cancer Inst 97 (7): 471-2, 2005. [PUBMED Abstract]
  38. Ganz PA, Greendale GA, Petersen L, et al.: Managing menopausal symptoms in breast cancer survivors: results of a randomized controlled trial. J Natl Cancer Inst 92 (13): 1054-64, 2000. [PUBMED Abstract]
  39. Feller WF, Holt R, Spear S, et al.: Modified radical mastectomy with immediate breast reconstruction. Am Surg 52 (3): 129-33, 1986. [PUBMED Abstract]
  40. Cunningham BL: Breast reconstruction following mastectomy. In: Najarian JS, Delaney JP, eds.: Advances in Breast and Endocrine Surgery. Chicago, Ill: Year Book Medical Publishers, 1986, pp 213-226. [PUBMED Abstract]
  41. Scanlon EF: The role of reconstruction in breast cancer. Cancer 68 (5 Suppl): 1144-7, 1991. [PUBMED Abstract]
  42. Hang-Fu L, Snyderman RK: State-of-the-art breast reconstruction. Cancer 68 (5 Suppl): 1148-56, 1991. [PUBMED Abstract]
  43. Kuske RR, Schuster R, Klein E, et al.: Radiotherapy and breast reconstruction: clinical results and dosimetry. Int J Radiat Oncol Biol Phys 21 (2): 339-46, 1991. [PUBMED Abstract]
  44. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. JAMA 271 (20): 1587-92, 1994. [PUBMED Abstract]
  45. Rosselli Del Turco M, Palli D, Cariddi A, et al.: Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up. JAMA 271 (20): 1593-7, 1994. [PUBMED Abstract]
  46. Khatcheressian JL, Wolff AC, Smith TJ, et al.: American Society of Clinical Oncology 2006 update of the breast cancer follow-up and management guidelines in the adjuvant setting. J Clin Oncol 24 (31): 5091-7, 2006. [PUBMED Abstract]


Cellular Classification of Breast Cancer

Back Up

The following is a list of breast cancer histologic classifications. 1 Infiltrating or invasive ductal cancer is the most common breast cancer histologic type and comprises 70% to 80% of all cases.

  • Carcinoma, NOS (not otherwise specified).
  • Ductal.
    • Intraductal (in situ).
    • Invasive with predominant intraductal component.
    • Invasive, NOS.
    • Comedo.
    • Inflammatory.
    • Medullary with lymphocytic infiltrate.
    • Mucinous (colloid).
    • Papillary.
    • Scirrhous.
    • Tubular.
    • Other.

  • Lobular.
    • In situ.
    • 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.

The following are tumor subtypes that occur in the breast but are not considered to be 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. [PUBMED Abstract]
  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

Back Up

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 primarily according to tumor size, lymph node status, estrogen-receptor and progesterone-receptor levels in the tumor tissue, human epidermal growth factor receptor 2 (HER2/neu) status, menopausal status, and the general health of the patient.


Definitions of TNM

The AJCC has designated staging by TNM classification to define breast cancer. 1 When this system was modified in 2002, some nodal categories that were previously considered stage II were reclassified as stage III. 2 As a result of the stage migration phenomenon, survival by stage for case series classified by the new system will appear superior to those using the old system. 3


Table 1. Primary Tumor (T)a,b

in situ; LCIS = lobular carcinoma in situ. aReprinted with permission from AJCC: 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.bThe T classification of the primary tumor is the same regardless of whether it is based on clinical or pathologic criteria, or both. Size should be measured to the nearest millimeter. If the tumor size is slightly less than or greater than a cutoff for a given T classification, it is recommended that the size be rounded to the millimeter reading that is closest to the cutoff. For example, a reported size of 1.1 mm is reported as 1 mm, or a size of 2.01 cm is reported as 2.0 cm. Designation should be made with the subscript "c" or "p" modifier to indicate whether the T classification was determined by clinical (physical examination or radiologic) or pathologic measurements, respectively. In general, pathologic determination should take precedence over clinical determination of T size.cInvasion of the dermis alone does not qualify as T4.
TX  Primary tumor cannot be assessed. 
T0  No evidence of primary tumor. 
Tis  Carcinoma in situ. 
Tis (DCIS)  DCIS. 
Tis (LCIS)  LCIS. 
Tis (Paget)  Paget disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) 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. 
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 skin nodules).c 
T4a  Extension to the chest wall, not including only pectoralis muscle adherence/invasion. 
T4b  Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d'orange) of the skin, which do not meet the criteria for inflammatory carcinoma. 
T4c  Both T4a and T4b. 
T4d  Inflammatory carcinoma.  
DCIS = ductal carcinoma  
 
 
 


Table 2. Regional Lymph Nodes (N)a

aReprinted with permission from AJCC: 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.bClinically detected is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination. Confirmation of clinically detected metastatic disease by fine needle aspiration without excision biopsy is designated with an (f) suffix, for example, cN3a(f). Excisional biopsy of a lymph node or biopsy of a sentinel node, in the absence of assignment of a pT, is classified as a clinical N, for example, cN1. Information regarding the confirmation of the nodal status will be designated in site-specific factors as clinical, fine needle aspiration, core biopsy, or sentinel lymph node biopsy. Pathologic classification (pN) is used for excision or sentinel lymph node biopsy only in conjunction with a pathologic T assignment.
Clinical 
NX  Regional lymph nodes cannot be assessed (e.g., previously removed). 
N0  No regional lymph node metastases. 
N1  Metastases to movable ipsilateral level I, II axillary lymph node(s). 
N2  Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted.  
OR 
Metastases in clinically detectedb ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases. 
N2a  Metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures. 
N2b  Metastases only in clinically detectedb ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastases. 
N3  Metastases in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I, II axillary lymph node involvement.  
OR 
Metastases in clinically detectedb ipsilateral internal mammary lymph node(s) with clinically evident level I, II axillary lymph node metastases. 
OR 
Metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. 
N3a  Metastases in ipsilateral infraclavicular lymph node(s). 
N3b   Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s). 
N3c  Metastases in ipsilateral supraclavicular lymph node(s). 
 
 


Table 3. Pathologic (pN)a,b

aReprinted with permission from AJCC: 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.bClassification is based on axillary lymph node dissection with or without sentinel lymph node biopsy. Classification based solely on sentinel lymph node biopsy without subsequent axillary lymph node dissection is designated (SN) for "sentinel node," for example, pN0(SN).c"Not clinically detected" is defined as not detected by imaging studies (excluding lymphoscintigraphy) or not detected by clinical examination.d"Clinically detected" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis based on fine-needle aspiration biopsy with cytologic examination.
pNX  Regional lymph nodes cannot be assessed (e.g., previously removed or not removed for pathologic study). 
pN0  No regional lymph node metastasis identified histologically. 
Note: ITCs are defined as small clusters of cells 0.2 mm, or single tumor cells, or a cluster of <200 cells in a single histologic cross-section. ITCs may be detected by routine histology or by IHC methods. Nodes containing only ITCs are excluded from the total positive node count for purposes of N classification but should be included in the total number of nodes evaluated. 
pN0(i)  No regional lymph node metastases histologically, negative IHC. 
pN0(i+)  Malignant cells in regional lymph node(s) 0.2 mm (detected by H&E or IHC including ITC). 
pN0(mol)  No regional lymph node metastases histologically, negative molecular findings (RT-PCR). 
pN0(mol+)  Positive molecular findings (RT-PCR), but no regional lymph node metastases detected by histology or IHC. 
pN1  Micrometastases. 
OR 
Metastases in 13 axillary lymph nodes. 
AND/OR 
Metastases in internal mammary nodes with metastases detected by sentinel lymph node biopsy but not clinically detected.c 
pN1mi  Micrometastases (>0.2 mm and/or >200 cells but none >2.0 mm). 
pN1a  Metastases in 13 axillary lymph nodes, at least one metastasis >2.0 mm. 
pN1b  Metastases in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected.c 
pN1c  Metastases in 13 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected. 
pN2  Metastases in 49 axillary lymph nodes. 
OR 
Metastases in clinically detectedd internal mammary lymph nodes in the absence of axillary lymph node metastases. 
pN2a  Metastases in 49 axillary lymph nodes (at least 1 tumor deposit >2 mm). 
pN2b  Metastases in clinically detectedd internal mammary lymph nodes in the absence of axillary lymph node metastases. 
pN3  Metastases in 10 axillary lymph nodes. 
OR 
Metastases in infraclavicular (level III axillary) lymph nodes.  
OR 
Metastases in clinically detectedc ipsilateral internal mammary lymph nodes in the presence of one or more positive level I, II axillary lymph nodes.  
OR 
Metastases in >3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected.c  
OR 
Metastases in ipsilateral supraclavicular lymph nodes. 
pN3a  Metastases in 10 axillary lymph nodes (at least 1 tumor deposit >2.0 mm). 
OR 
Metastases to the infraclavicular (level III axillary lymph) nodes. 
pN3b  Metastases in clinically detectedd ipsilateral internal mammary lymph nodes in the presence of one or more positive axillary lymph nodes;  
OR 
Metastases in >3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected.c 
pN3c  Metastases in ipsilateral supraclavicular lymph nodes. 
Posttreatment ypN 
Posttreatment yp "N" should be evaluated as for clinical (pretreatment) "N" methods above. The modifier "SN" is used only if a sentinel node evaluation was performed after treatment. If no subscript is attached, it is assumed that the axillary nodal evaluation was by AND. 
The X classification will be used (ypNX) if no yp posttreatment SN or AND was performed. 
N categories are the same as those used for pN. 
AND = axillary node dissection; H&E = hematoxylin and eosin stain; IHC = immunohistochemical; ITC = isolated tumor cells; RT-PCR = reverse transcriptase/polymerase chain reaction. 
 
 
 
 


Table 4. Distant Metastases (M)a

aReprinted with permission from AJCC: 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.
M0  No clinical or radiographic evidence of distant metastases. 
cM0(i+)  No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are 0.2 mm in a patient without symptoms or signs of metastases. 
M1  Distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven >0.2 mm. 
 

Posttreatment yp M classification. The M category for patients treated with neoadjuvant therapy is the category assigned in the clinical stage, prior to initiation of neoadjuvant therapy. Identification of distant metastases after the start of therapy in cases where pretherapy evaluation showed no metastases is considered progression of disease. If a patient was designated to have detectable distant metastases (M1) before chemotherapy, the patient will be designated as M1 throughout. 1


Table 5. Anatomic Stage/Prognostic Groupsa,b

aReprinted with permission from AJCC: 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.bT1 includes T1mi.cT0 and T1 tumors with nodal micrometastases only are excluded from Stage IIA and are classified Stage IB.
Stage  T  N  M 
0  Tis  N0  M0 
IA  T1b  N0  M0 
IB  T0  N1mi  M0 
  T1b  N1mi  M0 
IIA  T0  N1c  M0 
  T1b  N1c  M0 
  T2  N0  M0 
IIB  T2  N1  M0 
  T3  N0  M0 
IIIA  T0  N2  M0 
  T1b  N2  M0 
  T2  N2  M0 
  T3  N1  M0 
  T3  N2  M0 
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