1/ #BreastRadPath with @DrJordanaP

For this tweetorial we are going to talk about how we evaluate the biomarkers ER, PR, and HER2.

@BIDMCpath @BIDMC_BreastImg @CollinsLauraC @ADamronMD @GuzmanArocho @XeniaParisi @MarcosLepeMD @DrGeeONE @smlungpathguy
2/ The biomarkers provide predictive information (how a patient may respond to targeted therapy) as well as prognostic information. It helps to organize patients into treatment groups that follow different algorithms and guidelines.
3/ Biomarkers are evaluated in routine clinical mgmt of patients with breast cancer. The 3 routinely tested:

Hormone receptors (HR): Estrogen receptor (ER) and Progesterone receptor (PR)
Human epidermal growth factor receptor 2 (HER2)

(chart from: bit.ly/3lPbqoY)
4/ We use the testing guidelines from the American Society for Clinical Oncology (ASCO) and the College of American Pathologists (CAP). They include technical information about how the tissue should be handled. 👇
5/ ER and PR: Most recent guidelines published in 2020 (updated from 2010) bit.ly/36Xpo3s

HER2: Most recent guidelines published in 2018 (first released in 2007 and updated in 2013) bit.ly/36XLqTV
6/ We use immunohistochemistry (IHC) to determine ER and PR status by staining ER/PR receptors in the nuclei. Guidelines require that IHC reports include: % of tumor cells with nuclear staining, intensity of staining (weak, moderate, strong), & interpretation (pos vs neg).
7/ ER & PR result categories:
Positive: ≥1% of tumor nuclei staining
Negative: <1% of tumor nuclei staining
For ER, there is a “low positive category” --> 1-10% of nuclei staining
8/ For example, this case of an invasive lobular carcinoma (H&E stain on left) is: ER positive, >95% of nuclei are staining with strong intensity (the brown dots on the right). (PR positive would look similar).
9/ ER is also routinely evaluated in ductal carcinoma in situ.
10/ HER2 can be evaluated by different methods. HER2 protein overexpression is assessed by IHC. HER2 gene amplification is assessed by in situ hybridization (ISH). There are different types of ISH, we do FISH (fluorescent ISH).
11/ For evaluation by IHC we evaluate the cell membrane staining to look for HER2 protein expression.
12/ Here is an example of a HER2 positive invasive ductal carcinoma showing 3+ membrane staining. To me, in positive cases, it looks like someone took a sharpie and drew around each cell.
13/ For HER2 gene amplification the gene copies of HER2 (on chromosome 17) are compared to CEP17 (centromeric region of chromosome 17). See the flow chart from the guidelines to see how we interpret the results.
14/ Here is an example of a breast cancer with amplified (FISH positive) HER2 --> each cell (blue circle) has many more red dots than green dots.
15/ Many institutions start with IHC and only send the 2+ equivocal cases for FISH to classify HER2. Most of the cases will fall into FISH positive (group 1) or negative (group 5). We send both IHC and FISH on all of our cases of invasive breast cancer.
16/ Cases that fall into the non-classical FISH groups (groups 2, 3 and 4) we use IHC result and the group number to help classify. It is a bit complicated so see table below 👇
17/ These are the three routine biomarkers we do on every case of invasive carcinoma. We perform these studies on the core needle biopsy and sometimes on the excision. We also perform them in cases of metastatic breast carcinoma so it can help guide treatment.
18/ There are pitfalls and other considerations, but we can address those in a future post!

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More from @LizaMQuintana

14 Oct
#breastradpath with @DrJordanaP

For #BreastCancerAwarenessMonth month we want to review the process from imaging to diagnosis of breast cancer. 1/ Image
It starts when a patient comes in for a screening or diagnostic mammogram. Here is @DrJordanaP reviewing #mammograms in the reading room. 2/ Image
Please review screening modalities in this amazing tweetorial from last week from @DrJordanaP! 3/

Read 24 tweets
28 Sep
Case 3 #breastradpath with @DrJordanaP

44 yo woman. On req: "faint grouped microcalcs." #breastimagers separate calcs and no calcs cores into separate containers (so helpful!). There was only one block of cores with calcs. Here are the #breastpath images. Thoughts? Next steps? ImageImage
You are all thinking the way I did! For cases with calcs, I always review the imaging, and in particular the specimen radiograph, to see the morphology of the calcs I should look for. Check out the imaging from @DrJordanaP 👇

The tiny calc in the initial levels of the CNB are not the same as the calcs seen on imaging. We need to find those calcs --> LEVELS! (I haven't heard it called steps before! I like!) #breastradpath correlation is so important here! ImageImage
Read 11 tweets
17 Sep
Hi #pathology tweeples! I just realized that the callus I have on my pinky is from using it to steady my hand as I dot 😂(with my green pen of course 😉). I must dot A LOT! 💪🔬

I have some #path (mostly) dotting related questions out of curiosity.

@BIDMCpath Image
The #pathology tweeples have very strong opinions about dotting pen color! My tweet is inspired by this from @Chucktowndoc
Does anyone else have a dotting pen-induced callus? (Just me? I hope I'm not alone. 🤞😊)
Read 11 tweets
15 Sep
#breastradpath with @DrJordanaP

We are excited to share the first case in our #breastimaging and #breastpath correlation series! This case highlights challenges of imaging/management and the pathologic diagnosis.

@BIDMC_BreastImg @BIDMCpath #radres #radfellows Image
56 yo woman with left breast focal asymmetry and calcifications. Screening mammogram. @DrJordanaP Image
Diagnostic mammogram and ultrasound were performed. A presumed ultrasound correlate was found with calcs and vascularity. What is the next step? What BI-RADS would give? @DrJordanaP ImageImage
Read 17 tweets
19 Mar
Breast biopsy for calcs. What is your diagnosis? Would you do stains? Since I’m asking that means I did 😉🔬 #breastpath @BIDMCpath @CollinsLauraC @jennpincus @RanaAldreesMD @tlabiano @lara_pijuan @ADamronMD @ariella8 @kis_lorand @TheISBP ImageImageImageImage
Thanks for all the comments! Here are the stain. All (including p120, not pictured) were consistent with a lobular phenotype. ImageImage
There were some hints in the background with areas of classical LCIS. ImageImage
Read 6 tweets
10 Mar
Breast excision. What is your diagnosis? Would you do stains? #breastpath ImageImageImage
Thanks everyone! This is LCIS involving collagenous spherulosis. I did IHC. The e-cad was stronger than I expected but showed granular staining so I followed up with p120 and beta-catenin to illustrate the different stains.
Read 5 tweets

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