Old women with a breast lesion.

Fig 1 20x

Fig 2-3: 100x

Fig 4-5: 200x

Fig 6. 400x

What are your differential diagnoses?

I suddenly notice that I made a typing mistake about the classification. Sorry about this.

I describe the concept again

Gene expression profiling studies identified various breast carcinoma classes with prognostic significance. The 5 distinct classes indentified by expression progiling include 1)luminal A, 2)luminal B, 3)Her2 overexpression, 4) basal-like, 5) normal breast-like. Remember this classification was based on the many gene expression resutls. We can call them as genotypes of breast cancer.

Genotypes of Breast Cancer and Correponding Immunophenotype Markers

Genotype                            Immunophenotypic Marker

Luminal A                            ER+, and/or PR+, Her2-

Luminal B                            ER+, and/or PR+, Her2+

Her2 overexpressing                  ER-, PR-, /Her2+

Basal-like                           ER-PR-Her2-                     

                                     positive for some markers  

                                    (CK5/6, EGFR, CK14, 17)

Normal breast-like                No immunophenotypic marker.

 Happy to see some study about basa-like ca in China

Liu H, Fan Q, Zhang Z, Li X, Yu H, Meng F.

Department of Pathology, Nanjing Medical University, Nanjing 210029, PR China.

 continue.

7. Prognosis

Basal-like breast carcinoma (BBC) associated with high grade, poor prognosis.

Given the triple-negative status of basal-like breast cancer, it cannot be treated with ER-targeted or HER2-targeted therapies, so is primarily treated with chemotherapy. Fortunately, advances in adjuvant therapy appear to benefit ER-negative breast cancer even more than ER-positive breast cancer, and women with the basal-like subtype have similarly benefited.

The women with pathologic complete response have good outcome; the poor prognosis of basal-like breast cancer appears to relate to a particularly high risk of early distant relapse among those that had residual disease.

8.

Remember the classification and our previous classification are two different systems. In the US, people still use the previous classification, such as invasive ducat ca, lobular ca, mucinous ca, tubular ca….

For the basal-like breast carcinoma like my case, I sign out as invasive ductal carcinoma, basal-like phenotype.

 Continue:

4. Rate:

Accounting for about 15% of all breast carcinoma. It over-presented in young African American women who developed breast ca, comprising 39 of breast ca.

5. Genetic:

Related to BRCA1 mutation, but be aware that most basal-like ca patients are sporadic.

6.

Relation to medullary carcinoma (MBC):

Relation to medullary carcinoma (MBC):

One study shows that MBC belongs to the basal molecular subtype. Basal subtype can be subdivided in at least two subgroups: MBCs and basal DBCs. (François Bertucci et al Gene Expression Profiling Shows Medullary Breast Cancer Is a Subgroup of Basal Breast Cancers Cancer Research 66, 4636-4644, May 1, 2006).

In fact MBC is very rare. We seldom make this dx now. Please think over before you want to disgnose MBC. The clinician will think the patient has a good tumor. Every day we have about 20 breast core biopsies and about 15 breast segmental or total mastectomies, We almost never diagnose MBC in recent years.

In addition, I think most metaplastic carcinoma may belong to the group of basal-like ca also.

 Continue:

3. Typical Pathologic features: solid growth pattern, high nuclear grade, presence of marked lymphocytic infiltrate, and geographic necrosis. It is not necessary they must have above features.

A. Triple negative.

B: At least one of basal-like markers is positive, CK5/6 or EGFR, or other basal-like marker CK14, CK17, CD63, 34bE12, We generally use CK5/6 (or CK5), EGFR, CK14, CK17 as a panel. Some use only CK5/6 and EGFR. In fact a lot of cases show EGFR negative or weakly positive. My colleague, Dr. Bhargava demonstrated CK5 is the most sensitive marker (Am J Clin Pathol. 2008 Nov;130(5):724-30).

We do ER/PR/Her2 for all invasive tumors. If triple negative, then basal-like markers will be done for all cases.

 Seem many of you know this entity well. I almost  finished my  preparation to our fellows next week. I reviewed some papers and summaried the main points here for your reference.

1. The origin of the terminology

Gene expression analyses with cDNA microarray technology identified distinct groups of breast cancers. Based on the patterns of expression of 534 intrinsic genes, the breast carcinoma were sub-classified in to 5 groups, Luminal A, Luminal B, Basal-like, Her2 over-expression, and normal breast-like.

Open to see the original papers in 2001, 2003 if you are really interested

 http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=166244&blobtype=pdf

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=58566&blobtype=pdf

2. The relation between IHC stains and microarray gene classification: tumors by ER and Her2:

Tumors with ER expression could be divided into two groups “luminal A” and “luminal B” and no ER expression could be divided into three subgroups: "basal-like" subtype, HER2-positive subtype, and "normal breast-like".

So total five subgroups:

Luminal A: ER+/Her2+

Luminal B: ER+/Her2-

Basal-like: ER-/Her2-

Her2 over expression: ER-/Her2+

Normal breast-like: ER- ...?

 IHC results

F1 ck5

F2 ck14

F3 ck17

F4 EGFR

F5 Ki67

Hope every one can make your dx. please write down u questions or have some discussion. I will have a relatively detailed discussion here sometimes next week. Now I need to prepare a formal powerpoint presentation to our fellows and residents next week.

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 Saw you above response. Can you make the final dx based on morphology and IHC results I showed you?

I hope every one can write down your dx and reasons. I am interested in knowing your thinking. Then I know what I should discuss. Internet is good. You can write what you want to and you do not have any responsibility. I do not know any one of you. It is a free stage for every one.

Anyway I will discuss this topic in details later.

ER and PR stains

Her 2 also negative