Difference between revisions of "BRST5:Secretory Carcinoma"

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{{Under Construction}}
 
 
==Primary Author(s)*==
 
==Primary Author(s)*==
  
−
Put your text here
+
Hui Chen, MD, PhD, The University of Texas MD Anderson Cancer Center
 +
 
 +
Morteza Seifi, PhD, University of Wisconsin
  
 
__TOC__
 
__TOC__
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==Cancer Category/Type==
 
==Cancer Category/Type==
  
−
Put your text here
+
Breast Tumours /  Epithelial tumours of the breast
  
 
==Cancer Sub-Classification / Subtype==
 
==Cancer Sub-Classification / Subtype==
  
−
Put your text here
+
Rare and salivary gland-type tumours / Secretory carcinoma
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
  
−
Put your text here
+
Secretory carcinoma is a low-grade tumor displaying pushing borders and areas of unequivocal stromal invasion. Tumors may show combinations of microcystic, solid and tubular patterns. The microcystic pattern is composed of irregular shaped small cysts lined with single layer of tumor cells and filled with eosinophilic secretions. The tubular pattern shows luminal eosinophil secretions. The microcystic and tubular patterns can mimic thyroid follicles and can merge into solid islands. Tumor cells are polygonal with granular eosinophilic to foamy cytoplasm. Tumor nuclei are slightly enlarged and regular in shape with inconspicuous nucleoli. Mitotic activity is rare.
  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
  
−
Put your text here
+
Synonyms: Juvenile breast carcinoma (historical)
  
 
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
  
−
Put your text here
+
Rare, < 0.02% of all breast cancers. <ref name=":0">{{Cite journal|last=Horowitz|first=David P.|last2=Sharma|first2=Charu S.|last3=Connolly|first3=Eileen|last4=Gidea-Addeo|first4=Daniela|last5=Deutsch|first5=Israel|date=2012-06|title=Secretory carcinoma of the breast: results from the survival, epidemiology and end results database|url=https://pubmed.ncbi.nlm.nih.gov/22494666|journal=Breast (Edinburgh, Scotland)|volume=21|issue=3|pages=350–353|doi=10.1016/j.breast.2012.02.013|issn=1532-3080|pmid=22494666}}</ref><ref name=":1">{{Cite journal|last=Jacob|first=John Doromal|last2=Hodge|first2=Caitlin|last3=Franko|first3=Jan|last4=Pezzi|first4=Christopher M.|last5=Goldman|first5=Charles D.|last6=Klimberg|first6=Vicki Suzanne|date=2016-06|title=Rare breast cancer: 246 invasive secretory carcinomas from the National Cancer Data Base|url=https://pubmed.ncbi.nlm.nih.gov/27040042|journal=Journal of Surgical Oncology|volume=113|issue=7|pages=721–725|doi=10.1002/jso.24241|issn=1096-9098|pmid=27040042}}</ref>
 +
 
 +
Initially described in children; most common childhood breast cancer. <ref>{{Cite journal|last=McDivitt|first=R. W.|last2=Stewart|first2=F. W.|date=1966-01-31|title=Breast carcinoma in children|url=https://pubmed.ncbi.nlm.nih.gov/4285563|journal=JAMA|volume=195|issue=5|pages=388–390|issn=0098-7484|pmid=4285563}}</ref>
 +
 
 +
Wide age range, bimodal age distribution with peaks in second and seventh decades <ref name=":0" />
 +
 
 +
M:F = 1:6 to 1:31. <ref name=":1" /><ref>{{Cite journal|last=Arce|first=C.|last2=Cortes-Padilla|first2=D.|last3=Huntsman|first3=D. G.|last4=Miller|first4=M. A.|last5=Dueñnas-Gonzalez|first5=A.|last6=Alvarado|first6=A.|last7=Pérez|first7=V.|last8=Gallardo-Rincón|first8=D.|last9=Lara-Medina|first9=F.|date=2005-06-17|title=Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/15963235|journal=World Journal of Surgical Oncology|volume=3|pages=35|doi=10.1186/1477-7819-3-35|issn=1477-7819|pmc=1184104|pmid=15963235}}</ref><ref>{{Cite journal|last=Li|first=Dali|last2=Xiao|first2=Xiuying|last3=Yang|first3=Wentao|last4=Shui|first4=Ruohong|last5=Tu|first5=Xiaoyu|last6=Lu|first6=Hongfen|last7=Shi|first7=Daren|date=2012-04|title=Secretory breast carcinoma: a clinicopathological and immunophenotypic study of 15 cases with a review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/22157932|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=25|issue=4|pages=567–575|doi=10.1038/modpathol.2011.190|issn=1530-0285|pmid=22157932}}</ref><ref>{{Cite journal|last=Herz|first=H.|last2=Cooke|first2=B.|last3=Goldstein|first3=D.|date=2000-10|title=Metastatic secretory breast cancer. Non-responsiveness to chemotherapy: case report and review of the literature|url=https://pubmed.ncbi.nlm.nih.gov/11106125|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=11|issue=10|pages=1343–1347|doi=10.1023/a:1008387800525|issn=0923-7534|pmid=11106125}}</ref> 
  
 
==Clinical Features==
 
==Clinical Features==
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{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
−
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
+
|Well-circumscribed mobile masses
−
 
 
−
EXAMPLE B-symptoms (weight loss, fever, night sweats)
 
−
 
 
−
EXAMPLE Fatigue
 
−
 
 
−
EXAMPLE Lymphadenopathy (uncommon)
 
 
|-
 
|-
 
|'''Laboratory Findings'''
 
|'''Laboratory Findings'''
−
|EXAMPLE Cytopenias
+
|Not applicable
−
 
 
−
EXAMPLE Lymphocytosis (low level)
 
 
|}
 
|}
  
 
==Sites of Involvement==
 
==Sites of Involvement==
  
−
Put your text here
+
The tumors are commonly seen in sub-areolar area.
  
 
==Morphologic Features==
 
==Morphologic Features==
  
−
Put your text here
+
Microcystic, solid and tubular patterns
  
 
==Immunophenotype==
 
==Immunophenotype==
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
−
|Positive (universal)||EXAMPLE CD1
+
|Positive (universal)||S100, EMA, TRK
 
|-
 
|-
−
|Positive (subset)||EXAMPLE CD2
+
|Positive (subset)||CEA (polyclonal), mammaglobin, SOX10
 
|-
 
|-
−
|Negative (universal)||EXAMPLE CD3
+
|Negative (universal)||ER, PR, and HER2
 
|-
 
|-
−
|Negative (subset)||EXAMPLE CD4
+
|Negative (subset)||
 
|}
 
|}
  
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
+
|t(12;15)(p13;q25)||''ETV6::NTRK3''||der(15)||92% <ref name=":2" />
−
EXAMPLE 30% (add reference)
 
 
|Yes
 
|Yes
−
|No
 
 
|Yes
 
|Yes
−
|EXAMPLE
+
|Yes
−
 
+
|The ''ETV6::NTRK3'' fusion is diagnostic of secretory carcinoma of breast in the appropriate morphology and clinical context. <ref name=":2">{{Cite journal|last=Tognon|first=Cristina|last2=Knezevich|first2=Stevan R.|last3=Huntsman|first3=David|last4=Roskelley|first4=Calvin D.|last5=Melnyk|first5=Natalya|last6=Mathers|first6=Joan A.|last7=Becker|first7=Laurence|last8=Carneiro|first8=Fatima|last9=MacPherson|first9=Nicol|date=2002-11|title=Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma|url=https://pubmed.ncbi.nlm.nih.gov/12450792|journal=Cancer Cell|volume=2|issue=5|pages=367–376|doi=10.1016/s1535-6108(02)00180-0|issn=1535-6108|pmid=12450792}}</ref> This fusion is responsive to targeted therapy such as larotrectinib (Vitrakvi) and  entrectinib (Rozlytrek). <ref>{{Cite journal|last=Krebs|first=M. G.|last2=Blay|first2=J.-Y.|last3=Le Tourneau|first3=C.|last4=Hong|first4=D.|last5=Veronese|first5=L.|last6=Antoniou|first6=M.|last7=Bennett|first7=I.|date=2021-04|title=Intrapatient comparisons of efficacy in a single-arm trial of entrectinib in tumour-agnostic indications|url=https://pubmed.ncbi.nlm.nih.gov/33676294|journal=ESMO open|volume=6|issue=2|pages=100072|doi=10.1016/j.esmoop.2021.100072|issn=2059-7029|pmc=8103537|pmid=33676294}}</ref>
−
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
 
 
|}
 
|}
 
 
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|N/A
−
 
+
|N/A
−
7
+
|N/A
−
|EXAMPLE Loss
+
|N/A
−
|EXAMPLE
+
|N/A
−
 
+
|N/A
−
chr7:1- 159,335,973 [hg38]
+
|N/A
−
|EXAMPLE
+
|N/A
−
 
 
−
chr7
 
−
|Yes
 
−
|Yes
 
−
|No
 
−
|EXAMPLE
 
−
 
 
−
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
 
|-
 
|-
−
|EXAMPLE
+
|
−
 
+
|
−
8
+
|
−
|EXAMPLE Gain
+
|
−
|EXAMPLE
+
|
−
 
+
|
−
chr8:1-145,138,636 [hg38]
+
|
−
|EXAMPLE
+
|
−
 
 
−
chr8
 
−
|No
 
−
|No
 
−
|No
 
−
|EXAMPLE
 
−
 
 
−
Common recurrent secondary finding for t(8;21) (add reference).
 
 
|}
 
|}
 
==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE
+
|N/A
−
 
+
|N/A
−
Co-deletion of 1p and 18q
+
|N/A
−
|Yes
+
|N/A
−
|No
+
|
−
|No
 
−
|EXAMPLE:
 
−
 
 
−
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
 
 
|}
 
|}
 
==Gene Mutations (SNV/INDEL)==
 
==Gene Mutations (SNV/INDEL)==
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!Notes
 
!Notes
 
|-
 
|-
−
|EXAMPLE: TP53; Variable LOF mutations
+
|N/A
−
 
+
|N/A
−
EXAMPLE:
+
|N/A
−
 
+
|N/A
−
EGFR; Exon 20 mutations
+
|N/A
−
 
+
|N/A
−
EXAMPLE: BRAF; Activating mutations
+
|N/A
−
|EXAMPLE: TSG
+
|N/A
−
|EXAMPLE: 20% (COSMIC)
 
−
 
 
−
EXAMPLE: 30% (add Reference)
 
−
|EXAMPLE: IDH1 R123H
 
−
|EXAMPLE: EGFR amplification
 
−
|
 
−
|
 
 
|
 
|
−
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
 
−
<br />
 
 
|}
 
|}
 
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
 
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
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==Epigenomic Alterations==
 
==Epigenomic Alterations==
  
−
Put your text here
+
N/A
  
 
==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
  
−
Put your text here and fill in the table
+
<br />
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|EXAMPLE: BRAF and MAP2K1; Activating mutations
+
|NTRK3 fusion; Activating mutations
−
|EXAMPLE: MAPK signaling
+
|Ras-Mek1 and PI3K-Akt pathways
−
|EXAMPLE: Increased cell growth and proliferation
+
|Increased cell growth and proliferation
 
|-
 
|-
−
|EXAMPLE: CDKN2A; Inactivating mutations
+
|
−
|EXAMPLE: Cell cycle regulation
+
|
−
|EXAMPLE: Unregulated cell division
+
|
 
|-
 
|-
−
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
+
|
−
|EXAMPLE:  Histone modification, chromatin remodeling
+
|
−
|EXAMPLE:  Abnormal gene expression program
+
|
 
|}
 
|}
 
==Genetic Diagnostic Testing Methods==
 
==Genetic Diagnostic Testing Methods==
  
−
Put your text here
+
FISH, RT-PCR, RNAseq
  
 
==Familial Forms==
 
==Familial Forms==
  
−
Put your text here
+
<br />
  
 
==Additional Information==
 
==Additional Information==
  
−
Put your text here
+
<br />
  
 
==Links==
 
==Links==
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===EXAMPLE Book===
 
===EXAMPLE Book===
  
−
#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.
+
#Secretory carcinoma, in World Health Organization Classification of Tumours of Breast Tumours, Revised 5th edition. Allison KH, Brogi E, Ellis IO, Fox SB, Morris EA, Sahin A, Salgado R, Sapino A, Sasano H, Schnitt SJ, Sotiriou C, van Diest PJ, Editorial board expert members. IARC Press: Lyon, France, p146-148.
  
 
==Notes==
 
==Notes==
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.
 
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

Latest revision as of 16:42, 16 April 2024

Primary Author(s)*

Hui Chen, MD, PhD, The University of Texas MD Anderson Cancer Center

Morteza Seifi, PhD, University of Wisconsin

Cancer Category/Type

Breast Tumours / Epithelial tumours of the breast

Cancer Sub-Classification / Subtype

Rare and salivary gland-type tumours / Secretory carcinoma

Definition / Description of Disease

Secretory carcinoma is a low-grade tumor displaying pushing borders and areas of unequivocal stromal invasion. Tumors may show combinations of microcystic, solid and tubular patterns. The microcystic pattern is composed of irregular shaped small cysts lined with single layer of tumor cells and filled with eosinophilic secretions. The tubular pattern shows luminal eosinophil secretions. The microcystic and tubular patterns can mimic thyroid follicles and can merge into solid islands. Tumor cells are polygonal with granular eosinophilic to foamy cytoplasm. Tumor nuclei are slightly enlarged and regular in shape with inconspicuous nucleoli. Mitotic activity is rare.

Synonyms / Terminology

Synonyms: Juvenile breast carcinoma (historical)

Epidemiology / Prevalence

Rare, < 0.02% of all breast cancers. [1][2]

Initially described in children; most common childhood breast cancer. [3]

Wide age range, bimodal age distribution with peaks in second and seventh decades [1]

M:F = 1:6 to 1:31. [2][4][5][6]

Clinical Features

Put your text here and fill in the table

Signs and Symptoms Well-circumscribed mobile masses
Laboratory Findings Not applicable

Sites of Involvement

The tumors are commonly seen in sub-areolar area.

Morphologic Features

Microcystic, solid and tubular patterns

Immunophenotype

Put your text here and fill in the table

Finding Marker
Positive (universal) S100, EMA, TRK
Positive (subset) CEA (polyclonal), mammaglobin, SOX10
Negative (universal) ER, PR, and HER2
Negative (subset)

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
t(12;15)(p13;q25) ETV6::NTRK3 der(15) 92% [7] Yes Yes Yes The ETV6::NTRK3 fusion is diagnostic of secretory carcinoma of breast in the appropriate morphology and clinical context. [7] This fusion is responsive to targeted therapy such as larotrectinib (Vitrakvi) and  entrectinib (Rozlytrek). [8]

Individual Region Genomic Gain/Loss/LOH

Put your text here and fill in the table

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
N/A N/A N/A N/A N/A N/A N/A N/A

Characteristic Chromosomal Patterns

Put your text here

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
N/A N/A N/A N/A

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table

Gene; Genetic Alteration Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other) Prevalence (COSMIC / TCGA / Other) Concomitant Mutations Mutually Exclusive Mutations Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
N/A N/A N/A N/A N/A N/A N/A N/A

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

N/A

Genes and Main Pathways Involved


Gene; Genetic Alteration Pathway Pathophysiologic Outcome
NTRK3 fusion; Activating mutations Ras-Mek1 and PI3K-Akt pathways Increased cell growth and proliferation

Genetic Diagnostic Testing Methods

FISH, RT-PCR, RNAseq

Familial Forms


Additional Information


Links

Put your text placeholder here (use "Link" icon at top of page)

References

  1. ↑ 1.0 1.1 Horowitz, David P.; et al. (2012-06). "Secretory carcinoma of the breast: results from the survival, epidemiology and end results database". Breast (Edinburgh, Scotland). 21 (3): 350–353. doi:10.1016/j.breast.2012.02.013. ISSN 1532-3080. PMID 22494666. Check date values in: |date= (help)
  2. ↑ 2.0 2.1 Jacob, John Doromal; et al. (2016-06). "Rare breast cancer: 246 invasive secretory carcinomas from the National Cancer Data Base". Journal of Surgical Oncology. 113 (7): 721–725. doi:10.1002/jso.24241. ISSN 1096-9098. PMID 27040042. Check date values in: |date= (help)
  3. ↑ McDivitt, R. W.; et al. (1966-01-31). "Breast carcinoma in children". JAMA. 195 (5): 388–390. ISSN 0098-7484. PMID 4285563.
  4. ↑ Arce, C.; et al. (2005-06-17). "Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature". World Journal of Surgical Oncology. 3: 35. doi:10.1186/1477-7819-3-35. ISSN 1477-7819. PMC 1184104. PMID 15963235.
  5. ↑ Li, Dali; et al. (2012-04). "Secretory breast carcinoma: a clinicopathological and immunophenotypic study of 15 cases with a review of the literature". Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc. 25 (4): 567–575. doi:10.1038/modpathol.2011.190. ISSN 1530-0285. PMID 22157932. Check date values in: |date= (help)
  6. ↑ Herz, H.; et al. (2000-10). "Metastatic secretory breast cancer. Non-responsiveness to chemotherapy: case report and review of the literature". Annals of Oncology: Official Journal of the European Society for Medical Oncology. 11 (10): 1343–1347. doi:10.1023/a:1008387800525. ISSN 0923-7534. PMID 11106125. Check date values in: |date= (help)
  7. ↑ 7.0 7.1 Tognon, Cristina; et al. (2002-11). "Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma". Cancer Cell. 2 (5): 367–376. doi:10.1016/s1535-6108(02)00180-0. ISSN 1535-6108. PMID 12450792. Check date values in: |date= (help)
  8. ↑ Krebs, M. G.; et al. (2021-04). "Intrapatient comparisons of efficacy in a single-arm trial of entrectinib in tumour-agnostic indications". ESMO open. 6 (2): 100072. doi:10.1016/j.esmoop.2021.100072. ISSN 2059-7029. PMC 8103537 Check |pmc= value (help). PMID 33676294 Check |pmid= value (help). Check date values in: |date= (help)

(use "Cite" icon at top of page)

EXAMPLE Book

  1. Secretory carcinoma, in World Health Organization Classification of Tumours of Breast Tumours, Revised 5th edition. Allison KH, Brogi E, Ellis IO, Fox SB, Morris EA, Sahin A, Salgado R, Sapino A, Sasano H, Schnitt SJ, Sotiriou C, van Diest PJ, Editorial board expert members. IARC Press: Lyon, France, p146-148.

Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

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