Invasive breast cancer

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The article deals with invasive breast cancer and the evaluation of hormone receptor & HER2 status. Non-invasive breast cancer is dealt with in non-invasive breast cancer.

Introduction

Overview of invasive breast cancer subtypes

Common epithelial subtypes

Type and percentage of breast carcinomas:[1]

Common stromal types

Comprehensive list of invasive breast cancer subtypes

Epithelial

Counterparts of in situ lesions:

Other epithelial tumours:

Epithelial tumours seen in the salivary gland:

Seen in the skin:

Clinically diagnosed:

  • Inflammatory carcinoma.

In situ lesions:

Proliferative lesions:

Non-specific:

  • Microinvasive carcinoma.

Papillary:

  • Papilloma.
  • Atypical papilloma.
  • Intraductal papillary carcinoma.

Adenomas:

  • Ductal adenoma.
  • Tubular adenoma.
  • Lactating adenoma.
  • Apocrine adenoma.
  • Pleomorphic adenoma.

Myoepithelial

  • Myoepitheliosis.
  • Adenomyoepithelial adenosis.
  • Adenomyoepithelioma.
  • Malignant adenomyoepithelioma.

Mesenchymal tumours

See: Soft tissue lesions.

Fibroepithelial tumours

Nipple lesions

Other

Familial breast cancer

BRCA1 vs. BRCA2:[3]

Gene Age Histology Other cancers
BRCA1 younger worse types, e.g. triple negative breast ca. uterine tube
BRCA2 older sporadic types stomach, melanoma, gallbladder, bile duct, pharynx

Types of cancer assoc. with both BRCA1 and BRCA2:

  • Ovarian, male breast, prostate, pancreas.

Breast IHC

Molecular classification of invasive carcinoma

A molecular classification:[4]

Type Percentage IHC Histology Prognosis/clinical
Luminal A ~45% ER+ PR+ HER2- well-differentiated good, chemo resistant
Luminal B 17% ER+ PR+ HER2+ high grade poor, +/- chemo responsive
Normal breast-like ~8% ER+ PR+ (?) HER2- well-differentiated good
Basal-like ~20% ER- PR- HER2- poorly differentiated aggressive, may have good chemo response
HER2 positive ~10% ER- PR- (?) HER2+ poorly differentiated poor

The above is not applied clinically. IHC (ER, PR, HER2, EGFR, CK5/6) can reproduce the molecular groupings and has been proposed as a way to applied the classification.[5]

Subtyping breast cancer

  • DCIS vs LCIS:[6]
    • E-cadherin (+ve DCIS, -ve LCIS).
    • antibody 34betaE12 (+ve perinuclear LCIS, -ve DCIS).
    • CAM5.2 (peripheral stain = DCIS, perinuclear stain = LCIS).
      • CAM5.2 is against CK8.
    • Beta-catenin (-LCIS, +DCIS).
  • D2-40:[7][8]
    • Monoclonal antibody to podoplanin.
    • Useful to assess lymphovascular invasion.
  • ADH and DCIS:[9]
    • E-cadherin.
      • Present in most epithelial cells.
      • Lost in LCIS & invasive lobular carcinoma.
    • SMMHC (smooth muscle cell myosin heavy chain).
      • Marks myoepithelial cells.

Treatment-related markers - overview

  • Immunostaining of any sentinel lymph nodes - to look for isolated tumour cells and small lymph node mets.
    • Sunnybrook uses CAM5.2.
  • ER (estrogen receptor).
    • Positive in most breast cancers; +ve in ~75-80%.[10]
  • PR (progesterone receptor).
    • Positive in most breast cancers; +ve in ~65-70%.[10]
  • HER2/neu.
    • Usually negative; -ve in 70-80%.[10]
    • Positivity association with a worse prognosis.

ER & PR scoring[10]

  • Give a percentage, i.e. 0-100%.
    • Important cut points: 1% and 10%.
      • 0% = negative - not treated.
      • <10% = low positivity - treated.

Notes:

  • Normal breast epithelial cells have a patchy staining for ER and PR.
  • Evaluated on the invasive component.

HER2 scoring

Immunohistochemical based testing:[10][11][12]

Score Staining intensity Cells stained (%) Membrane staining Management Percentage of cases
0 nil <10% incomplete No HER2 blocker ~60%
1+ minimum >10% incomplete No HER2 blocker ~10%
2+ weak >10% complete Needs SISH or FISH ~10%
3+ uniform staining (used to be strong) >30% (used to >10%) complete HER2 blocker ~20%

Notes 1:

  • Normal breast epithelial cells do not stain with HER2.
  • Evaluated on the invasive component.
  • SISH = silver in situ hybridization.
  • FISH = fluorescence in situ hybridization.

ISH based testing:[11]

Result Ratio criteria Gene copy number criteria
Positive >2.2 HER2/CEP17 >6.0 copies of HER2/cell
Equivocal 1.8-2.2 HER2/CEP17 4.0-6.0 copies of HER2/cell
Negative <1.8 HER2/CEP17 <4.0 copies of HER2/cell

Notes 2:

  • Can be called positive based on either ratio criteria or gene copy number criteria.

Clinical

  • ER & PR status determine whether a patient will get tamoxifen or other estrogen receptor modulators, such as raloxifene (Evista).
  • HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.

Characteristics of the subtypes

Invasive ductal carcinoma of the breast

  • AKA "NST" = No Specific Type.
  • AKA invasive mammary carcinoma.

General

  • Most common type of invasive breast cancer.

Microscopic

Features:

  • Cohesive cells.
    • Forming ducts or sheets.
  • Nuclear pleomorphism.
    • Nucleoli common.

IHC

Typically:

  • ER +ve.
  • PR +ve.
  • HER2 -ve.

Invasive lobular carcinoma

  • Abbreviated ILC.
  • AKA lobular carcinoma.

General

  • May be associated with a CDH-1 mutation - seen in diffuse type gastric cancer.[13]

Microscopic

Features:

  • "Single file" - cell line-up in a row.
    • Cell should not be cohesive -- lymphoma should briefly come to mind.
      • primary lymphoma of the breast exists... but it is extremely rare.
  • NO gland formation.
    • If it forms glands... it is more likely NST.
  • May have signet ring morphology.
  • NO desmoplastic reaction, i.e. the stroma surrounding the tumour cells should look benign and undisturbed.

Note:

  • commonly have low grade nuclear features

Images:

Subclassification:

  • Classic lobular carcinoma.
    • Low nuclear grade - NO significant variation of nucleus size.
  • Pleomorphic lobular carcinoma.
    • Significant nuclear atypia.

Note: Some pathologist grade lobular carcinoma like other types and avoid the term "pleomorphic lobular carcinoma."[14]

Medullary breast carcinoma

  • AKA medullary carcinoma of the breast.

General

  • Some pathologists don't believe this exists.

Epidemiology:

  • Thought to have a better prognosis that no special type (NST).
  • Association with BRCA1 mutations.

Microscopic

Features:

  1. Lesion has well-circumscribed border.
  2. Syncytial growth pattern = clumps of cells with poorly defined cell borders.
  3. Lymphocytic infiltrate.
  4. High nuclear grade (as per Nottingham grading system).
  5. No tubule formation.

Tubular carcinoma of the breast

  • AKA tubular carcinoma.

General

Epidemiology:

  • Typically excellent prognosis.
  • Hormone receptors commonly present.

Note:

  • May be seen in association with lobular carcinoma in situ and columnar cell lesions - known as Rosen triad.[15]
    • Memory device TLC = Tubular ca., LCIS, Columnar cell lesions.

Microscopic

Features:[16][17][18]

  • Well-formed tubules.
  • Myoepithelial cells absent.
  • +/- Cribriform spaces.
  • Apocrine snouts typical.
  • +/- Calcification.
  • Angled ducts common: "prows" - important feature (low power).
  • Looks benign to the uninitiated -- IMPORTANT.

Notes:

  • Prow = front of a ship.

DDx:

Image:

Metaplastic breast carcinoma

  • AKA metaplastic carcinoma.

General

  • May be difficult to diagnose.
  • Prognosis - poor.

Microscopic

Features - one of the following:[19][20]

  1. Malignant mesenchymal elements - either:
    1. Spindle cells.
    2. Osseous, chondroid or rhabdoid differentiation.
  2. Squamous component.

Images:

Subclassification

  • There are various way to subclassify this subtype of breast cancer. This a consequence of physician automomy.
    • There is a series of articles on the topic by Wargotz & Norris that is quite old... yet it is mentioned in Sterberg:[21]
    1. Matrix-producing carcinoma:[22]
      • Features: cartilaginous and/or osseous stromal matrix; no osteoclastic giant cells.
    2. Spindle cell carcinoma:[23]
      • Features: (non-malignant) spindle cells.
      • Prognosis: better prognosis than other metaplastic carcinomas.
    3. Carcinosarcoma:[24]
      • Features: malignant mesenchymal element.
      • Prognosis: survival worse when compared to other metaplastic carcinomas.
    4. Squamous cell carcinoma of ductal origin:[25]
      • Features: purely squamous; metastases are squamous cell carcinoma.
    5. Metaplastic carcinoma with osteoclastic giant cells:[26]
    • The WHO subclassifies as follows:[27]
    1. Epithelial - includes: squamous cell carcinoma, adenocarcinoma with spindle cell differentiation, adenosquamous carcinoma.
    2. Mixed epithelial and mesenchymal - includes: carcinosarcoma, carcinoma with metaplasia (chondroid, osseous).

IHC

  • S100 -ve (r/o melanoma).
  • AE1/AE3 +ve (epithelial elements only).
  • CK7 +ve (epithelial elements only).
  • p63 +ve (epithelial elements only).
  • Vimentin +ve.
  • Desmin -ve.
  • EMA -ve. (???)

Invasive micropapillary carcinoma of the breast

  • AKA micropapillary carcinoma.

General

  • Poor prognosis.
  • LVI common.[28]

Microscopic

Features:

  • Clear spaces/clefting around (small) nests of tumour - diffuse/through-out the tumour - key feature.
    • Described as "small clusters of tumour lying within dilated vascular channel-like spaces".[29]

Note:

  • Ductal carcinoma commonly has clefting... but it isn't diffuse.

IHC

  • EMA +ve (periphery of nests); described as inside-out pattern.[29]
  • E-cadherin +ve (centre of nests). (???)
  • p63 +ve/-ve.

Apocrine carcinoma of the breast

General

  • Need >=90% apocrine morphology.[30]

Microscopic

Features:[30]

  • Prominent nucleoli.
  • Abundant granular eosinophilic cytoplasm.
  • Architecture like invasive ductal carcinomas no special type.

Images:

IHC

Smaller tumours classically:[32]

  • AR +ve.
  • GCDFP-15 +ve.

Usually:[30]

  • ER -ve.
  • PR -ve.

Mucinous breast carcinoma

  • AKA mucinous carcinoma of the breast, AKA colloid carcinoma of the breast.

General

  • Rare.
  • Good prognosis.[33]

Microscopic

Features:

  • Mucin producing glands.
    • Should comprise >90% of the tumour.[34]

Note:

Adenoid cystic carcinoma of the breast

  • AKA breast adenoid cystic carcinoma.

General

Microscopic

See: Adenoid cystic carcinoma article.

DDx:

Images:

Invasive papillary carcinoma of the breast

  • AKA intracystic papillary carcinoma of the breast.
  • AKA encapsulated papillary carcinoma of the breast.

General

  • Very good prognosis.
  • Classical menopausal women.
  • ~30% present with bloody discharge.[36]

Microscopic

Features:

  • Lesion confined to a duct (intraductal) or cyst (intracystic).
    • May have a thick fibrous capsule = encapsulated papillary carcinoma.[36]
  • Loss of myoepithelial cells - key feature.
  • Neoplastic epithelial cells:

Glycogen-rich clear cell carcinoma of the breast

  • Abbreviated GRCC.

General

Microscopic

Features:

  • Groups of cells with abundant clear cytoplasm - need to comprise 90% of the tumour.[38]
    • Various architectural arrangements: cords, trabeculae, clusters, cribriform.
    • Minimal nuclear pleomorphism.

Notes:

DDx:

  • Signet-ring carcinoma.
  • Lipid-rich carcinoma.
  • Apocrine carcinoma.
  • Secretory carcinoma.

Image:

Stains

Features:[38]

  • PAS +ve.
  • PASD -ve.

Others:[38]

  • Oil red O -ve.
    • Lipid-rich carcinoma +ve.

IHC

Features:[38]

  • BRST2 -ve.
    • Apocrine carcinoma +ve.

Grading breast cancer

Most common system: Nottingham (aka Scarff-Bloom-Richardson) which is based on:

  1. Nuclear grade.
    • Small, regular (1.5-2x RBC dia.) = 1.
    • Moderated variability = 2.
    • Marked variation (>2.5x RBC dia.) = 3.
  2. Tubule formation.
    • Majority of tumour - tubules >75% = 1.
    • Moderate - 10% to 75% = 2.
    • Minimal <10% = 3.
  3. Mitotic rate.
    • 0-5 mitosis/10 HPF (1.52 mm^2 --or-- 0.0152 mm^2 * 10) = 1.
    • 6-10 mitosis/10 HPF (1.52 mm^2) = 2.
    • >11 mitosis/10 HPF (1.52 mm^2) = 3.

Mnemonic: TMN = tubule formation, mitotic rate, nuclear grade.

Notes:

  • Elston & Ellis devised the system that is used.[39] They also wrote a follow-up article in 2002.[40]

Note about mitosis counting

  • One MUST adjust for the size of the field of view.
  • Most of the Resident scopes have an eye piece diameter of 22 mm. Therefore, the field diameter at 40 X is approximately 22 mm / 40 X ~= 0.55 mm and the field of view is pi/4*(0.55 mm)^2 = 0.2376 mm^2.
    • Thus, on a resident scope (with a FOV of 0.2376 mm^2) one should sample 6 or 7 fields of view (FsOV).
      • Calculation: 1.52 mm^2 (sampling area) / 0.2376 mm^2 (area / FOV ) = 6.40 FsOV.
  • RANT: Sampling 10 fields, where the field of view (FOV) is 0.152 mm^2, is not the same as sampling ten fields, where the FOV is 0.312 mm^2. It surprises me that Elston & Ellis ignore the fact that "10 HPFs" on different microscopes represent different sample areas and that they do not standardize the sampling area.

Calculating Nottingham score

  • Grade I = 3-5 points.
  • Grade II = 6-7 points.
  • Grade III = 8-9 points.

Notes:

  • I've found most tumours are grade II.
  • The mitotic score is usually 1/3.
  • The nuclear score is rarely 1/3 -- even in the tubular subtype.[41]

Staging breast cancer

Definitions:[42]

  • Isolated tumour cells: <=0.2 mm and <200 cells.
  • Micrometastasis: <=0.2 cm and ( >0.2 mm or >=200 cells ).

Tumour:[43][44]

  • pT1: <= 2 cm.
    • pT1mic <= 0.1 cm.
    • pT1a > 0.1 cm and <= 0.5 cm.
    • pT1b > 0.5 cm and <= 1.0 cm.
    • pT1c > 1.0 cm and <= 2.0 cm.
  • pT2: > 2 cm and <= 5 cm
  • pT3: > 5 cm.
  • pT4: chest wall or skin involvement.

Lymph nodes:[45]

  • pN0: nil.
    • pN0(i+): <=0.2 mm and <200 cells.
  • pN1: 1-3 axillary LNs or internal mammary LNs.
    • pN1mi: <=0.2 cm and ( >0.2 mm or >=200 cells ).
    • pN1a.
    • pN1b.
    • PN1c.
  • pN2 4-9 positive LNs; internal mammary LNs or axillary LNs.
  • pN3.

Lymphovascular invasion

There are famous criteria for lymphovascular invasion (LVI).

Rosen criteria for LVI:[46][47]

  1. Must be outside of the tumour proper.
    • LVI is usually very close -- typically within 0.1 cm.
  2. Contour of cells should differ from possible vessel wall.
    • DCIS with retraction artifact mimicing LVI has a contour that matches its surrounding fibrous tissue.
  3. Endothelium (usu. flat) should be visible.
  4. Lymphatics are found adjacent to blood vessels - vessels should be present in the vicinity.

Memory device LUBE-O:

  • LVI has a Unique contour, Blood vessels and Endothelium in the vicinity, and is Outside of the tumour.

Other

Paget's disease

Main article: Paget disease of the breast

General

  • Associated with underlying breast carcinoma.[48]

Notes:

Microscopic

Features:[48]

  • Cells in the epidermis:
    • Epitheliod morphology (round/ovoid).
    • Cells nested or single.
    • Clear/pale cytoplasm key feature - may also be eosinophilic.
    • Large nucleoli.

Images:

IHC & DDx:

Sentinel lymph node biopsy

General

  • Used for staging, positive LNs = poorer prognosis.

Notes:

  • If there is no palpable disease, there is no mortality benefit from axillary lymph node dissection, i.e. positive axillary lymph nodes can be left in situ without affecting outcome.[49]
    • This does not negate the fact that a positive sentinel LN biopsy (vs. negative sentinel LN biopsy) portends a poorer prognosis.

Microscopic

Features:

  • Atypical cells.
    • Nuclear changes of malignancy:
      • Nuclear enlargement + variation in size.
      • Variation in shape.
      • Hyperchromasia and variation in staining.
    • Usually in the subcapsular sinuses.

Pitfalls:

  • Naevus cell rests.[50]

IHC

Some hospitals use:

  • CAM5.2 (LMWK) - to look for isolated tumour cells and small lymph node metstases.

Trivia

Tumour size and lymph node metastases

There is a paper[51] that calculates the probability of lymph node mets based on tumour size. The developed formula is:

Where:

  • = the probability of the lymph nodes being positive.
  • D = the largest dimension of the tumour in millimetres.
  • Z = 1.0041.
  • = 0.019.

Selected values

Tumour size (mm) Probability
5 9 %
10 17 %
15 25 %
20 32 %
25 38 %
30 44 %
35 49 %
40 54 %
45 58 %
50 62 %

Natural history

There is a theory that up to 22% of small (radiographically detected) breast tumours regress, based on an analysis in a large population.[52] The study is supported by NCI's SEER data.[53] Also, it generated many comments.[52]

Missed macrometastases

The effect of missed macrometastases is small; this implies using IHC to look for isolated tumour cells is money that isn't well spent.[54]

See also

References

  1. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1143. ISBN 0-7216-0187-1.
  2. ↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html. Accessed on: 28 November 2010.
  3. ↑ Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Jon (2009). Robbins and Cotran pathologic basis of disease (8th ed.). Elsevier Saunders. pp. 1078. ISBN 978-1416031215.
  4. ↑ Mitchell, Richard; Kumar, Vinay; Fausto, Nelson; Abbas, Abul K.; Aster, Jon (2011). Pocket Companion to Robbins & Cotran Pathologic Basis of Disease (8th ed.). Elsevier Saunders. pp. 547. ISBN 978-1416054542.
  5. ↑ Tang, P.; Skinner, KA.; Hicks, DG. (Sep 2009). "Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready?". Diagn Mol Pathol 18 (3): 125-32. doi:10.1097/PDM.0b013e31818d107b. PMID 19704256.
  6. ↑ Yeh IT, Mies C (March 2008). "Application of immunohistochemistry to breast lesions". Arch. Pathol. Lab. Med. 132 (3): 349-58. PMID 18318578. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349.
  7. ↑ Ordóñez NG (March 2006). "Podoplanin: a novel diagnostic immunohistochemical marker". Adv Anat Pathol 13 (2): 83-8. doi:10.1097/01.pap.0000213007.48479.94. PMID 16670463.
  8. ↑ Kahn HJ, Marks A (September 2002). "A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors". Lab. Invest. 82 (9): 1255-7. PMID 12218087.
  9. ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 122. ISBN 978-0443066450.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 241-2. ISBN 978-0443066450.
  11. ↑ 11.0 11.1 Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 87. ISBN 978-0-323-06516-0.
  12. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 27 November 2011.
  13. ↑ URL: http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33006. Accessed on: 19 April 2011.
  14. ↑ MUA. Jan 22, 2009.
  15. ↑ Brandt, SM.; Young, GQ.; Hoda, SA. (May 2008). "The "Rosen Triad": tubular carcinoma, lobular carcinoma in situ, and columnar cell lesions.". Adv Anat Pathol 15 (3): 140-6. doi:10.1097/PAP.0b013e31816ff313. PMID 18434766.
  16. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1146. ISBN 0-7216-0187-1.
  17. ↑ URL: http://www.bweems.com/nsj3mp2.jpg.
  18. ↑ URL: http://surgpathcriteria.stanford.edu/breast/tubularcabr/.
  19. ↑ 19.0 19.1 URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html. Accessed on: 28 November 2010.
  20. ↑ Barnes, PJ.; Boutilier, R.; Chiasson, D.; Rayson, D. (May 2005). "Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu expression.". Breast Cancer Res Treat 91 (2): 173-8. doi:10.1007/s10549-004-7260-y. PMID 15868445.
  21. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Reuter, Victor E; Stoler, Mark H (2009). Sternberg's Diagnostic Surgical Pathology (5th ed.). Lippincott Williams & Wilkins. pp. 328. ISBN 978-0781779425.
  22. ↑ Wargotz, ES.; Norris, HJ. (Jul 1989). "Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma.". Hum Pathol 20 (7): 628-35. PMID 2544506.
  23. ↑ Wargotz, ES.; Deos, PH.; Norris, HJ. (Aug 1989). "Metaplastic carcinomas of the breast. II. Spindle cell carcinoma.". Hum Pathol 20 (8): 732-40. PMID 2473024.
  24. ↑ Wargotz, ES.; Norris, HJ. (Oct 1989). "Metaplastic carcinomas of the breast. III. Carcinosarcoma.". Cancer 64 (7): 1490-9. PMID 2776108.
  25. ↑ Wargotz, ES.; Norris, HJ. (Jan 1990). "Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin.". Cancer 65 (2): 272-6. PMID 2153044.
  26. ↑ Wargotz, ES.; Norris, HJ. (Nov 1990). "Metaplastic carcinomas of the breast: V. Metaplastic carcinoma with osteoclastic giant cells.". Hum Pathol 21 (11): 1142-50. PMID 2227922.
  27. ↑ O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 214. ISBN 978-0443066801.
  28. ↑ Yu, JI.; Choi, DH.; Park, W.; Huh, SJ.; Cho, EY.; Lim, YH.; Ahn, JS.; Yang, JH. et al. (Jun 2010). "Differences in prognostic factors and patterns of failure between invasive micropapillary carcinoma and invasive ductal carcinoma of the breast: matched case-control study.". Breast 19 (3): 231-7. doi:10.1016/j.breast.2010.01.020. PMID 20304650.
  29. ↑ 29.0 29.1 Yamaguchi, R.; Tanaka, M.; Kondo, K.; Yokoyama, T.; Kaneko, Y.; Yamaguchi, M.; Ogata, Y.; Nakashima, O. et al. (Aug 2010). "Characteristic morphology of invasive micropapillary carcinoma of the breast: an immunohistochemical analysis.". Jpn J Clin Oncol 40 (8): 781-7. doi:10.1093/jjco/hyq056. PMID 20444748.
  30. ↑ 30.0 30.1 30.2 O'Malley, Frances P.; Pinder, Sarah E. (2006). Breast Pathology: A Volume in Foundations in Diagnostic Pathology series (1st ed.). Churchill Livingstone. pp. 217. ISBN 978-0443066801.
  31. ↑ O'Malley, FP.; Bane, A. (Jan 2008). "An update on apocrine lesions of the breast.". Histopathology 52 (1): 3-10. doi:10.1111/j.1365-2559.2007.02888.x. PMID 18171412.
  32. ↑ Honma, N.; Takubo, K.; Akiyama, F.; Sawabe, M.; Arai, T.; Younes, M.; Kasumi, F.; Sakamoto, G. (Aug 2005). "Expression of GCDFP-15 and AR decreases in larger or node-positive apocrine carcinomas of the breast.". Histopathology 47 (2): 195-201. doi:10.1111/j.1365-2559.2005.02181.x. PMID 16045781.
  33. ↑ Barkley, CR.; Ligibel, JA.; Wong, JS.; Lipsitz, S.; Smith, BL.; Golshan, M. (Oct 2008). "Mucinous breast carcinoma: a large contemporary series.". Am J Surg 196 (4): 549-51. doi:10.1016/j.amjsurg.2008.06.013. PMID 18809061.
  34. ↑ Dogan, E.; Aksoy, S.; Dizdar, O.; Arslan, C.; Dede, DS.; Ozisik, Y.; Altundag, K.. "Pure mucinous carcinoma of the breast: a single center experience.". J BUON 16 (3): 565-7. PMID 22006768.
  35. ↑ 35.0 35.1 Boujelbene, N.; Khabir, A.; Boujelbene, N.; Jeanneret Sozzi, W.; Mirimanoff, RO.; Khanfir, K. (Dec 2011). "Clinical review - Breast adenoid cystic carcinoma.". Breast. doi:10.1016/j.breast.2011.11.006. PMID 22154460.
  36. ↑ 36.0 36.1 Rodríguez, MC.; Secades, AL.; Angulo, JM. (Nov 2010). "Best cases from the AFIP: intracystic papillary carcinoma of the breast.". Radiographics 30 (7): 2021-7. doi:10.1148/rg.307105003. PMID 21057133.
  37. ↑ Hayes, MM.; Seidman, JD.; Ashton, MA. (Aug 1995). "Glycogen-rich clear cell carcinoma of the breast. A clinicopathologic study of 21 cases.". Am J Surg Pathol 19 (8): 904-11. PMID 7611537.
  38. ↑ 38.0 38.1 38.2 38.3 38.4 Thondavadi, SR.; Krishnamurthy, J.; Gubbanna, VM.. "A case report of glycogen-rich clear cell carcinoma of breast.". Indian J Pathol Microbiol 53 (2): 374-5. doi:10.4103/0377-4929.64289. PMID 20551566.
  39. ↑ Elston CW, Ellis IO (September 2002). "Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. C. W. Elston & I. O. Ellis. Histopathology 1991; 19; 403-410". Histopathology 41 (3A): 151–2, discussion 152–3. PMID 12405945.
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  44. ↑ URL: http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging. Accessed on: 9 July 2010.
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  47. ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 5 August 2011.
  48. ↑ 48.0 48.1 URL: http://emedicine.medscape.com/article/1101235-diagnosis
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  50. ↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html. Accessed on: 28 November 2010.
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  54. ↑ Weaver, DL.; Ashikaga, T.; Krag, DN.; Skelly, JM.; Anderson, SJ.; Harlow, SP.; Julian, TB.; Mamounas, EP. et al. (Feb 2011). "Effect of occult metastases on survival in node-negative breast cancer.". N Engl J Med 364 (5): 412-21. doi:10.1056/NEJMoa1008108. PMID 21247310.

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