1. TNM Staging: Breast TONYA BRANDENBURG, MHA, CTR KENTUCKY CANCER REGISTRY

2. Overview  Anatomy  Common Terms  Changes in T,N,M Staging from AJCC 6 th edition to 7 th edition  Elements of Staging: TX-T4, Clinical N, Pathological N and M0-M1  Stage Groups and Prognostic Factors  Helpful Hints  Breast Examples

4. Breast Anatomic sites and subsites of the breast. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

5. Schematic diagram of the breast and regional lymph nodes. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

6. Common Terms  Duct carcinoma, NOS: The largest group of breast cancers. Duct carcinoma, NOS is not a specific histologic type because it lacks specific features that can be used to better classify the tumor  In Situ: A tumor that is confined to the duct system (ductular or lobular) and does not invade surrounding stroma  Invasive: A tumor that penetrates beyond the ductal basement membrane into the adjacent stroma of the breast parenchyma  Paget Disease: Paget disease of the nipple is a condition where the epidermis of the nipple is Infiltrated with neoplastic cells. ICD-O-3 classifies all mammary Paget disease as a malignant process with a malignant behavior(/3). Under the matrix system, only if the Paget disease is explicitly specified as in situ or non-invasive by the pathologist, code the behavior in situ (/2).

7. Changes in T,N,M Staging for Breast from 6 th edition to 7 th edition  Identification of specific imaging modalities that can be used to estimate clinical tumor size  Recommendations about sizing a tumor grossly and microscopically  Recommendations of use of clinical versus pathological tumor size in cases of neoadjuvant treatment  Estimating tumor size  Clarification of inflammatory cancer definition  Recommended use of Nottingham combined histologic grade

8. Changes continued  Tighter classification of isolated tumor cells and single cells  Use of (sn) modifier on when 6 or more sentinel nodes are identified on gross exam  Subdivision of Stage 1 tumors into Stage 1a and Stage 1b based on nodal micrometastases  Creation of new M0 (i+) category, for either disseminated cells in bone marrow, or circulating tumor cells, or cells found incidentally (such as ovaries that are removed prophylactically)

9. Elements of Staging: TX, T0, and Tis  TX: Primary tumor cannot be assessed  T0: No evidence of primary tumor  Tis: Carcinoma in situ (CIS)  Tis (DCIS): Ductal carcinoma in situ  Tis (LCIS): Lobular carcinoma in situ  Tis (Paget’s): Paget’s disease of the nipple without mass

10. Tis (Paget's) is defined as Paget's disease of the nipple with no tumor. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

11. Elements of Staging: T1  T1: Tumor 2 cm or less  T1mi : Tumor 1 mm or less  T1a Tumor > 1 mm but < 5 mm  T1b Tumor > 5 mm but < 10 mm  T1c Tumor > 10 mm but < 20 mm

12. Elements of Staging: T1mi  T1mi is defined as microinvasion 1 mm or less in greatest dimension  No focus more than 1 mm  If multiple foci of microinvasion, use largest to classify

13. The presence of multiple tumor foci of microinvasion (top of diagram) should be noted in parentheses. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

15. Elements of Staging: T2-T3  T2: Tumor > 2.0 cm but not more than 5.0 cm in greatest dimension  T3: Tumor more than 5.0 cm in greatest dimension

16. T2 (above dotted line) is defined as tumor more than 20 mm but not more than 50 mm in greatest dimension, and T3 (below dotted line) is defined as tumor more than 50 mm in greatest dimension. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

17. Elements of Staging: T4 (T4a, T4b,T4c, and T4d)  T4: Tumor of any size with direct extension to chest wall and/or skin  T4a: Extension to chest wall, NOT including pectoralis muscle adherence/invasion  T4b: Ulceration and/or ipsilateral satellite skin nodules and/or edema (including peau d’orange) of the skin, which do not meet criteria for inflammatory carcinoma  T4c: Both T4a and T4b  T4d: Inflammatory carcinoma

18. Inflammatory Carcinoma  Characterized by diffuse erythema and edema (Pea d’orange) involving a third or more of the skin of the breast  Palpable mass? Maybe, maybe not  Involvement of dermal lymphatics without clinical skin changes do not qualify as inflammatory carcinoma  Neither do locally advanced breast cancers directly invading the dermis or ulcerating the skin without clinical skin changes or tumor emboli in dermal lymphatics

19. T4 is defined as a tumor of any size with direct extension to chest wall and/or to the skin (ulceration or skin nodules). T4a (illustrated here) is extension to the chest wall, not including only pectoralis muscle adherence/invasion. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

20. T4b, illustrated here as satellite skin nodules, is defined as edema (including peau d’orange) of the skin, or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast. These do not meet the criteria for inflammatory carcinoma. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

21. T4b illustrated here as edema (including peau d’orange) of the skin. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

22. T4c is defined as both T4a and T4b. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

23. T4d is inflammatory carcinoma. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

24. Elements of Staging: NX, N0, N1, N2, N2a, and N2b Clinical  cNX: Regional LN cannot be assessed  cN0: No regional LN metastases  cN1: metastases to movable ipsilateral axillary lymph node(s)  cN2: Ipsilateral LNs fixed or matted OR in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axilla  cN2a: Ipsilateral axillary LNs fixed or matted to each other or other structures  cN2b: “Clinically apparent” ipsilateral internal mammary nodes in the ABSENCE of clinically evident axillary LNs

25. Elements of Staging: N3, N3a, N3b, and N3c Clinical  cN3: Ipsilateral infraclavicular LNs with or without axillary LN involvement, clinically apparent ipsilateral internal mammary LNs and axillary LNs, or Ipsilateral supraclavicular LNs with or without axillary or internal mammary LN involvement  cN3a: Ipsilateral infraclavicular LNs with or without axillary LN involvement  cN3b: Clinically apparent ipsilateral internal mammary LNs and axillary LNs  cN3c: Ipsilateral supraclavicular LNs with or without axillary or internal mammary LN involvement

26. N1 is defined as metastases in movable ipsilateral level I, II axillary lymph node(s). Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

27. N2a is defined as metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

28. N2b is defined as metastases only in clinically detected ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastases. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

29. N3a is defined as metastases in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I, II axillary lymph node involvement. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

30. N3b is defined as metastases in clinically detected ipsilateral internal mammary lymph node(s) and clinically evident axillary lymph node(s). Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

31. N3c is defined as metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

32. Elements of Staging: NX, N0, Pathological  pNX: Regional lymph nodes cannot be assessed  pN0: No regional lymph node metastases histologically  pN0 (i-): No regional lymph node metastases histologically, negative IHC  pN0 (i+): Malignant cells in regional lymph nodes, no greater than 0.2m (detected by H & E or IHC including ITC)  pN0 (mol -): No regional lymph node metastases histologically, negative molecular findings  pN0 (mol +): Positive molecular findings but no regional lymph node metastases histologically or by IHC

33. pN0(i + ) is defined as malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC including ITC). Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

34. Elements of Staging: N1 Pathological  pN1 mi Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm)  pN1a: metastases in 1 to 3 axillary LNs, at least one metastases greater than 2.0 mm  pN1b: metastases in internal mammary nodes with micrometastases or macrometastases detected by sentinel LND but NOT “clinically apparent”  pN1c: metastases in 1 to 3 axillary LNs and internal mammary LNs with micrometastases or macrometastases detected by sentinel LND but NOT “clinically apparent”

35. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

36. pN1b metastases in internal mammary nodes detected by sentinel lymph node biopsy but not clinically detected. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

37. pN1c illustrating 3 positive axillary lymph nodes and metastases in internal mammary lymph nodes detected by sentinel lymph node biopsy but not clinically detected. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

38. Elements of Staging: N2 Pathological  pN2a metastases in 4to 9 axillary lymph nodes (at least one tumor deposit greater than 2.0 mm)  pN2b metastases in clinically detected internal mammary lymph nodes in the ABSENCE of axillary lymph node metastases

39. pN2b illustrating metastases in clinically detected internal mammary nodes with no axillary lymph node involvement. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

40. Elements of Staging: N3 Pathological  pN3a: metastases in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm), OR metastases to the infraclavicular (level III axillary) lymph nodes  pN3b: metastases in clinically detected ipsilateral internal mammary LNs in the presence of 1 or more positive axillary LNs, OR in more than 3 axillary LNs and in internal mammary LNs with micrometastases or macrometastases detected by sentinel LND but NOT “clinically apparent”  pN3c metastases to ipsilateral supraclavicular lymph nodes

41. pN3b illustrated as metastases in clinically detected internal mammary nodes in the presence of 3 positive axillary lymph nodes. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

42. pN3b illustrated as metastases in 6 positive axillary lymph nodes and in one internal mammary lymph node with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

43. pN3c illustrated as metastases in ipsilateral supraclavicular lymph nodes. Compton, C.C., Byrd, D.R., et al., Editors. AJCC CancerStaging Atlas, 2nd Edition. New York: Springer, 2012. ©American Joint Committee on Cancer

44. Elements of Staging: MX, M0, and M1  MX: No longer exists in TNM Staging  M0: No distant metastases (Remember: not possible for pathologic staging)  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 no larger than 0.2mm in a patient without symptoms or signs of metastases  M1: Distant metastases

45. Stage Groups

46. Prognostic Factors for Breast  Paget’s disease  Estrogen receptor, Progesterone receptor, and test method (IHC, RT- PCR, other)  HER2 status and test method (IHC, FISH, CISH, RT-PCR, other)  Method of lymph node assessment (e.g., clinical, fine needle aspiration; core biopsy; sentinel lymph node biopsy/IHC of regional lymph nodes  Molecular studies of regional lymph nodes  Distant metastases method of detection (clinical, radiographic, biopsy)  Circulating Tumor Cells (CTC) and method of detection (RT-PCR, immunomagnetic separation, other)  Disseminated Tumor Cells (DTC; bone marrow micrometastases) and method of detection (RT-PCR, immunohistochemical, other)  Multi-gene signature score  Response to neoadjuvant therapy will be collected in the registry, but does not affect the post­ neoadjuvant stage

47. Hints for Breast  Please see notes on page 362 in TNM 7th edition, under the table for pathologic lymph nodes but above the table for distant metastasis  Also read pages 364 through 369 for useful information

48. Breast Case 1 Answers  Topography: C50.2  Histology: 8500/3  This case is one primary per rule M3 Clinical Staging cT1b cN0 cM0 Clinical Stage Group IA Pathological Staging pT1b pN0(i-) pMcM0 Pathologic Stage Group IA SEER Summary Stage: 1 - Localized

49. Breast Case 2 Answers  Topography: c50.4  Histology: 8500/3  This case is one primary per rule M3 Clinical Staging cT2 cN0 cM0 Clinical Stage Group IIA Pathological Staging pT2 pN0(i+) pMcM0 Pathologic Stage Group IIA SEER Summary Stage: 1 - Localized