Invasive breast cancer
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
Types of invasive breast cancer
Common epithelial types
Type and percentage of breast carcinomas:[1]
- Ductal - AKA no special type (NST) - 79%.
- Lobular 10%.
- Cribriform (tubular) 6%.
- Mucinous (colloid) 2%.
- Medullary 2%.
- Papillary 1%.
- Metaplastic <1%.
Classic stromal
- Angiosarcoma - post-radiation ~ 10 years.[2]
Familial breast cancer
BRCA1 vs. BRCA2:[3]
- BRCA1:
- Younger.
- Ovarian cancer.
- Worse types of breast cancer (e.g. triple negative breast cancer: PR-, ER-, HER2/neu-).
- BRCA2:
- Older.
- Like sporatic.
- Male breast cancer.
- BOTH are associated with increased risk of (memory device CPP):
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).
- 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.
- E-cadherin.
- 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.
- Important cut points: 1% and 10%.
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
List of subtypes
Epithelial
Counterparts of in situ lesions:
- Invasive ductal carinoma, not otherwise specified.
- Invasive lobular carcinoma.
- Invasive cribriform carcinoma.
- Invasive papillary carcinoma.
- Invasive micropapillary carcinoma.
Other epithelial tumours:
- Tubular carcinoma.
- Medullary carcinoma.
- Mucinous carinoma.
- Metaplastic carcinoma.
- Neuroendocrine tumour.
- Apocrine carcinoma.
- Lipid-rich carcinoma.
- Secretory carcinoma.
- Oncocytic carcinoma.
- Glycogen-rich clear cell carcinoma.
Epithelial tumours seen in the salivary gland:
- Adenoid cystic carcinoma.
- Acinic cell carcinoma.
- Carcinoma ex pleomorphic adenoma.
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
- Fibroadenoma.
- Phyllodes tumour.
- Periductal stromal sarcoma, low grade.
- Mammary hamartoma.
Nipple lesions
- Nipple adenoma.
- Syringomatous adenoma.
- Paget disease of the breast.
Other
- Lymphoma.
- Metastasis.
Ductal carcinoma
- AKA "NST" = No Specific Type.
Microscopic
Features:
- Cohesive cells - forming ducts or in sheets.
- Nuclear pleomorphism.
Clinical
- Typically: ER+, PR+, HER2-.
Lobular carcinoma
General
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.
- Cell should not be cohesive -- lymphoma should briefly come to mind.
- 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:
- Lobular carcinoma - low mag. (WC).
- Lobular carcinoma - high mag. (WC).
- Lobular carcinoma - 1 (WC).
- Lobular carcinoma - 2 (WC).
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 carcinoma
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:
- Lesion has well-circumscribed border.
- Syncytial growth pattern = clumps of cells with poorly defined cell borders.
- Lymphocytic infiltrate.
- High nuclear grade (as per Nottingham grading system).
- No tubule formation.
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
- 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:
Metaplastic carcinoma
General
- May be difficult to diagnosis.
- Prognosis - poor.
Microscopic
Features:[19]
- Malignant mesenchymal elements:
- Spindle cells
- +/-Adenocarcinoma.
- +/-Squamous carcinoma.
Notes:
- If it looks like squamous cell carcinoma... in the breast it is metaplastic carcinoma.
Images: Metaplastic carcinoma (breastpathology.info).[19]
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:[20]
- Matrix-producing carcinoma:[21]
- Features: cartilaginous and/or osseous stromal matrix; no osteoclastic giant cells.
- Spindle cell carcinoma:[22]
- Features: (non-malignant) spindle cells.
- Prognosis: better prognosis than other metaplastic carcinomas.
- Carcinosarcoma:[23]
- Features: malignant mesenchymal element.
- Prognosis: survival worse when compared to other metaplastic carcinomas.
- Squamous cell carcinoma of ductal origin:[24]
- Features: purely squamous; metastases are squamous cell carcinoma.
- Metaplastic carcinoma with osteoclastic giant cells:[25]
- Features: osteoclastic giant cells.
- The WHO subclassifies as follows:[26]
- Epithelial - includes: squamous cell carcinoma, adenocarcinoma with spindle cell differentiation, adenosquamous carcinoma.
- 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. (???)
Micropapillary carcinoma
General
- Poor prognosis.
- LVI common.[27]
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".[28]
Note:
- Ductal carcinoma commonly has clefting... but it isn't diffuse.
IHC
- EMA +ve (periphery of nests); described as inside-out pattern.[28]
- E-cadherin +ve (centre of nests). (???)
- p63 +ve/-ve.
Apocrine carcinoma
General
- Need >=90% apocrine morphology.[29]
Microscopic
Features:[29]
- Prominent nucleoli.
- Often multiple.[30]
- Abundant granular eosinophilic cytoplasm.
- Architecture like invasive ductal carcinomas no special type.
Images:
IHC
Smaller tumours classically:[31]
- AR +ve.
- GCDFP-15 +ve.
Usually:[29]
- ER -ve.
- PR -ve.
Mucinous breast carcinoma
- AKA mucinous carcinoma of the breast.
General
- Rare.
- Good prognosis.[32]
Microscopic
Features:
- Mucin producing glands.
- Should comprise >90% of the tumour.[33]
Note:
- The amount of mucinous component to call mucinous carcinoma varies by anatomical site.
Grading breast cancer
Most common system: Nottingham (aka Scarff-Bloom-Richardson) which is based on:
- Nuclear grade.
- Small, regular (1.5-2x RBC dia.) = 1.
- Moderated variability = 2.
- Marked variation (>2.5x RBC dia.) = 3.
- Tubule formation.
- Majority of tumour - tubules >75% = 1.
- Moderate - 10% to 75% = 2.
- Minimal <10% = 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.[34] They also wrote a follow-up article in 2002.[35]
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.
- Thus, on a resident scope (with a FOV of 0.2376 mm^2) one should sample 6 or 7 fields of view (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.[36]
Staging breast cancer
Definitions:[37]
- Isolated tumour cells: <=0.2 mm and <200 cells.
- Micrometastasis: <=0.2 cm and ( >0.2 mm or >=200 cells ).
- 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:[40]
- 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:[41][42]
- Must be outside of the tumour proper.
- LVI is usually very close -- typically within 0.1 cm.
- Contour of cells should differ from possible vessel wall.
- DCIS with retraction artifact mimicing LVI has a contour that matches its surrounding fibrous tissue.
- Endothelium (usu. flat) should be visible.
- 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
General
- Associated with underlying breast carcinoma.[43]
Notes:
- Unrelated to Paget disease of the bone.
Microscopic
Features:[43]
- 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:
- See Paget disease.
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.[44]
- 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.
- Nuclear changes of malignancy:
Pitfalls:
- Naevus cell rests.[45]
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[46] 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.[47] The study is supported by NCI's SEER data.[48] Also, it generated many comments.[47]
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.[49]
See also
References
- ↑ 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.
- ↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html. Accessed on: 28 November 2010.
- ↑ 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. 1133. ISBN 0-7216-0187-1.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Lester, Susan Carole (2005). Manual of Surgical Pathology (2nd ed.). Saunders. pp. 122. ISBN 978-0443066450.
- ↑ 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.
- ↑ 11.0 11.1 Lester, Susan Carole (2010). Manual of Surgical Pathology (3rd ed.). Saunders. pp. 87. ISBN 978-0-323-06516-0.
- ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 27 November 2011.
- ↑ URL: http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=33006. Accessed on: 19 April 2011.
- ↑ MUA. Jan 22, 2009.
- ↑ 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.
- ↑ 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.
- ↑ URL: http://www.bweems.com/nsj3mp2.jpg.
- ↑ URL: http://surgpathcriteria.stanford.edu/breast/tubularcabr/.
- ↑ 19.0 19.1 URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_0807%20discussion.html. Accessed on: 28 November 2010.
- ↑ 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.
- ↑ Wargotz, ES.; Norris, HJ. (Jul 1989). "Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma.". Hum Pathol 20 (7): 628-35. PMID 2544506.
- ↑ 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.
- ↑ Wargotz, ES.; Norris, HJ. (Oct 1989). "Metaplastic carcinomas of the breast. III. Carcinosarcoma.". Cancer 64 (7): 1490-9. PMID 2776108.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 28.0 28.1 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.
- ↑ 29.0 29.1 29.2 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Elston CW, Ellis IO (November 1991). "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". Histopathology 19 (5): 403–10. PMID 1757079.
- ↑ MUA. 20 January 2009.
- ↑ URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
- ↑ URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
- ↑ URL: http://www.cancerhelp.org.uk/type/breast-cancer/treatment/tnm-breast-cancer-staging. Accessed on: 9 July 2010.
- ↑ URL: http://www.cancer.org/Cancer/BreastCancer/DetailedGuide/breast-cancer-staging. Accessed on: 8 July 2010.
- ↑ Rosen, PP. (1983). "Tumor emboli in intramammary lymphatics in breast carcinoma: pathologic criteria for diagnosis and clinical significance.". Pathol Annu 18 Pt 2: 215-32. PMID 6674861.
- ↑ URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf. Accessed on: 5 August 2011.
- ↑ 43.0 43.1 URL: http://emedicine.medscape.com/article/1101235-diagnosis
- ↑ Giuliano AE, Hunt KK, Ballman KV, et al. (February 2011). "Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial". JAMA 305 (6): 569–75. doi:10.1001/jama.2011.90. PMID 21304082.
- ↑ URL: http://www.breastpathology.info/Case_of_the_month/2007/COTM_1107%20discussion.html. Accessed on: 28 November 2010.
- ↑ Porembka, MR.; Abraham, RL.; Sefko, JA.; Deshpande, AD.; Jeffe, DB.; Margenthaler, JA. (Oct 2008). "Factors associated with lymph node assessment in ductal carcinoma in situ: analysis of 1988-2002 seer data.". Ann Surg Oncol 15 (10): 2709-19. doi:10.1245/s10434-008-9947-5. PMID 18483831. http://onlinelibrary.wiley.com/doi/10.1002/cncr.24592/pdf.
- ↑ 47.0 47.1 Zahl, PH.; Maehlen, J.; Welch, HG. (Nov 2008). "The natural history of invasive breast cancers detected by screening mammography.". Arch Intern Med 168 (21): 2311-6. doi:10.1001/archinte.168.21.2311. PMID 19029493.
- ↑ Jatoi, I.; Anderson, WF. (May 2009). "Breast cancer overdiagnosis with screening mammography.". Arch Intern Med 169 (10): 999-1000, author reply 1000-1. doi:10.1001/archinternmed.2009.95. PMID 19468099.
- ↑ 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.