Breast Cancer Workup

Clinical Work-up

* Hx (menstrual status, parity, family hx)
* Physical (breasts, axilla, supraclav, etc.) Clinical exam of nodes is wrong ~35% of the time.

  • Imaging Work-up
    • Mammo/US before Bx
    • X-Rays: Chest x-ray, CT chest, bone scan if indicated
  • Labs
    • CBC, LFT's, electrolytes
    • Path: Bloom-Richardson score, ER/PR, DNA index, S-phase, HER2/NEU

Staging

Primary Tumor Staging

PRIMARY TUMOR (T) Description
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis (DCIS) (LCIS) (Paget's) Carcinoma in situ
T1
T1 mic 0.1 cm or less
T1 a 0.1 - 0.5 cm
T1 b 0.5 - 1.0 cm
T1 c 1.0 - 2.0 cm
T2 2.0 - 5.0 cm
T3 > 5.0 cm
T4
T4a Extension to chest wall, not including pectoralis muscle
T4b Edema (including peau d'orange) or ulceration of skin or satellite skin nodules
T4c T4a & T4b together
T4d Inflammatory carcinoma

Clinical Lymph Node Staging

a b c
N1 movable AXL N2 fixed (matted) AXL
IMC but no AXL - N3 infraclavicular LN
IMC and AXL Supraclavicular LN

Pathologic Lymph Node Staging

  • pNX, regional LN cannot be assessed
  • pN0, no regional LN metastasis histologicaly, no additional examination for isolated tumor cells (ITC)
  • pN0 (i-), negative IHC
  • pN0 (i+), postive IHC
  • pN0 (mol-), RT-PCR negative
  • pN0 (mol+), RT-PCR positive
  • p N1 mi Micrometastasis (0.2 to 2.0 mm)
pathological stage a b c
pN1 1 - 3 ALN mic IMC by SLND pN1b + pN1a
pN2 4 - 9 ALN IMC (clinical) -
pN3 10+ ALN pN2b + pN1a/2a/3a
pN1b + pN2a/3a
Supraclavicular LN

AXL : ipsilateral axillary lymph nodes
LN: Lymph node
IMC: ipsilateral internal mammory lymph nodes
IHC: immunohisto chemistry

Notes

  • ITC found in sentinel LN in cases where the primary tumor is very small the probabillity of metastsis in a nonsentinel LN seems to be virtually zero.

Axillary LN Dissection

  • The minimum number of axillary lymph nodes to be removed in a level I/II node dissection is 6. [2]

Biopsy

Needle Biopsy

  • FNA
    • Immediate results
    • Cannot distinguish in situ from invasive cancer reliably
    • Requires skilled cytopathologist
  • Core biopsy
    • Should be recommended as it contains architectural information (invasion vs in situ) where as FNA does not.

Excisional biopsy

  • Core biopsy does not correlate with clinical data

Other Issues with Biopsy

  • Atypical ductal hyperplasia
    • when ADH is found in a needle biopsy, DCIS is found in 20-50% of cases in subsequent excisional biopsy.
  • Radial scar
  • Inadequate tissue sample
  • Wire Guided Biopsy

Negative biopsy results

  • If the clinical picture (ie. Mammogram/US/PE) is suspicious it must be confirmed positively by a core biopsy or excised. One can not be satisfied with a negative core in face of suspicion.
  • Mammo/ US after Excision
  • If the lesion was visible in imaging, re-image to show that the correct lesion was removed.

Sentinel Node Biopsy

  • Sentinel Lymph node biopsy for breast cancer was developed following successful use of the technique in the management of melanoma.
  • In general < 10% of patients with microSLN+ by IHC+ only will have macrometastasis on ALND.[4],[5]
  • For lobular carcinoma: IHC was associated with further nodal metastases in 12 of 50 cases (24%)[3]

Sentinel LN Dissection Trials

Italian (Veronesi) Randomized trial (NEJM 03; 349;6:546-53)

Dissection Regional Failure Rate Survival Patients with no arm swelling at 2 years # patients
Sentinel LN Dissection 1.0% 99% 96% 259
Axillary LD Dissection 1.6% 97% 25% 257
p-value N.S. N.S

Other Results of the Veronesi Trial

  • Sentinel LN group had less pain, numbness and arm swelling
  • 0% > 2 cm arm swelling in SLN group vs. 10% in ALND group.
  • Sensitivity 96.2%
  • Specificity 100%
  • False-negative rate 8.8%
  • Negative predictive value 95.4%

Pathologic classification

Ductal Carcinomas (DCIS)

  • DCIS with microinvasion (< 1 mm)
    • Prognosis is same as DCIS
  • Comedocarcinoma
  • Noncomedo
  • Cribriform

Papillary

  • Micropapillary

Paget’s
* DCIS extends from nipple ducts to skin
* Nipple and areola is frequently fissured, ulcerated, and oozing
* 50-60% cases have underlying mass which usually indicates carcinoma
* nipple involvement that may or may not have associated subaereolar mass.

IDC (invasive or infiltrating ductal carcinoma)

ILC (invasive lobular carcinoma)

  • 20% contralateral risk
  • Multicentric
  • Diffusely invasive pattern
  • Ones with better prognosis
  • Invasive papillary

Tubular

  • nonaggressivs
  • <10 % have + nodes
  • Rare death in stage I disease

Medullary

  • well circumscribed
  • infrequent nodes
  • 13% have BRCA1 gene
  • Do slightly better despite poor histological appearance

Mucinous/colloid

  • older pts
  • better survival than IDCa

Others

  • Cystosarcoma phyllodes
    • generally benign
    • large, and encapsulated
    • Slow growth then sudden increase in size.
    • Rare but reported mets.
  • Lymphoma
    • rare
    • usually non-Hodgkins B-cell.
  • PNET, SCCA, sarcoma, Adenoid cystic — rare
  • Metaplastic carcinoma : Carcinoma mixed with a mesenchymal or other non-epithelial component

HER2 STATUS

IHC and FISH

Percent FISH positive based in IHC score.[6]

  • 6556 breast tissues
IHC FISH
3+ 91.7 %
2+ 23.3%
1+ 7.4%
0 4.1%

Prognosis

5-OS for Patients with Breast Cancer[1]

Tumor Size No nodes (N0) 1-3 nodes (N1) 4+ nodes (N2 or N3)
< 2 cm (T1) 95% 90% 65%
< 5 cm (T2) 90% 80% 60%
5+ cm (T3 or T4) 80% 70% 45%
  • Axillary Lymph node has greater effect on survival than tumor size.
Bibliography
1. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989 Jan 1;63(1):181-7. PMID: 2910416
2. Recht A, et al. Regional nodal failure after conservative surgery and radiotherapy for early-stage breast carcinoma. Journal of Clinical Oncology. 1991;9(6):988-996.
3. Cserni G, Bianchi S, Vezzosi V, Peterse H, Sapino A, Arisio R, Reiner-Concin A, Regitnig P, Bellocq JP, Marin C, Bori R, Penuela JM, Iturriagagoitia AC. The value of cytokeratin immunohistochemistry in the evaluation of axillary sentinel lymph nodes in patients with lobular breast carcinoma. J Clin Pathol. 2006 May;59(5):518-22. Epub 2006 Feb 23. PMID: 16497870
4. Reynolds C, Mick R, Donohue JH, et al. Sentinel lymph node biopsy with metastasis: can axillary dissection be avoided in some patients with breast cancer? J Clin Oncol 1999;17:1720–1726.
5. Dabbs DJ, Fung M, Landsittel D, McManus K, Johnson R. Sentinel lymph node micrometastasis as a predictor of axillary tumor burden. Breast J. 2004 Mar-Apr;10(2):101-5. PMID: 15009035
6. Owens MA, Horten BC, Da Silva MM. HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004 Apr;5(1):63-9.
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