Thread by @TumorBoardTues

1/ 🗣️ #TumorBoardTuesday #Tweetorial

🧠 Prevalence, role, genomic testing 🧬HER family receptors
🥼 @MPishvaian @PancPathologist
Supported by educational grants from AstraZeneca Pharmaceuticals & Daiichii Sankyo, Inc.

🆓 #CME 👉 bit.ly/3Dxuh02

📊 Your specialty👇 ❓

2/ 🗒️ Full reference list & glossary 👉 bit.ly/3rKead3

🔑 Key #CME & faculty info 👇 , full info 👉 bit.ly/3Dxuh02

#TumorBoardTuesday

3/ 🧬 HER2 alteration occurs in multiple cancer types

🔎 Breast cancer (BC) ➡️ 25% of cases

🔎 Gastric cancer (GC) ➡️ 22%

🔎 Gastroesophageal junction (GEJxn) cancer ➡️ 32%

🔎 Colorectal cancer (CRC) ➡️ 5%

🔎 Non-small cell lung cancer (NSCLC) ➡️ 6%-30%
#TumorBoardTuesday

4/ 🛑 POLL 🛑

🤔 Which HER2 dimerization partner has been implicated in multiple mechanisms of Tx resistance ❓ #TumorBoardTuesday

5/ HER3 is correct! #TumorBoardTuesday

HER2
👉Essential active driver of aggressive tumors
👉Requires dimerization partner

HER3
👉Preferential dimerization w/ HER2
👉Ligand dependent/independent
👉Involved in multiple resistance mechanisms & ⬇️ downstream oncogenic signaling🚥

6/ HER2 molecular testing in BC

📌🆕 primary/newly met BC: IHC or ISH
🧪Reflex testing for equivocal results

📌HER2-low expression
Emerging HER2-targeted ADCs may be beneficial

📌HER2-low/➖🔀 may occur & affect 💊 Tx options & 🔬 Clinical trial enrollment
#TumorBoardTuesday

7/ 🛑 POLL 🛑

🤔 Which drug conjugated to trastuzumab (ADC) has demonstrated an objective response rate of 40% in patients w/ hormone receptor ➖, 🧬 HER2-low breast cancer ❓ #TumorBoardTuesday

8/ T-DXd is correct!

🔬Clinical trials demonstrated reduction in ADC-Tx HER2-low breast tumors

ORR 📈 w/
✅Trastuzumab deruxtecan (Ph1; n=47): HR➕ 28% (9/32); HR➖ 40% (6/15)
✅Trastuzumab duocarmazine (Ph1b; n=48): HR➕ 40.4% (19/47); HR➖ 14.3% (1/7)
#TumorBoardTuesday

9/HER2 🧪 testing in GC: IHC or ISH – NGS w/ limited tissue

GC vs BC: HER2 expression differences
👉 Staining pattern: U-shaped or lines 🆚 circumscribed
👉 Heterogeneous (patchy ➕ity) 🆚 homogeneous
👉 Variation w/ location: more frequent ➕ity in the GEJxn #TumorBoardTuesday

10/ In addition to 🧬 HER2 expression differences in GC 🆚 BC

📌 Cut points for IHC scoring also differ
📌 GC cut point: staining in a cluster of ≥ 5 tumor cells regardless of percentage➕
📌 BC cut point: staining in > 10% of tumor cells
#TumorBoardTuesday

11/ 🧬 HER2 in met NSCLC

🔜 Emerging biomarker
🔬 Correlates w/ adenoca histology
🧪 Molecular testing as part of panel preferred to single gene tests
👎 Insufficient evidence for cell-free circulating DNA🔄🧬
✅ Confirm ➖ results w/ tissue-based analysis
#TumorBoardTuesday

12/ 🛑 POLL 🛑

🤔 What is the current gold 🪙 standard for 🧬 HER2 molecular testing ❓ #TumorBoardTuesday

13/ FISH is the gold standard but 💲 & technically demanding

Other HER2 testing methods
👉IHC: most common; quick; may require confirmation
👉Other ISH: quick; more💲 than IHC, less common
👉NGS: can identify CNV; 🚫 recommended, longer turnaround than FISH
#TumorBoardTuesday

14/ 🕵️I-SPY2: Ph2⃣ trial - identify biomarkers of response to neoadjuvant Tx in 🧬 HER2+ early BC

💥 HER2 activation/phosphorylation in PreTx biopsy
💥 Associated w/ response to T-DM1/P & THP
💥 Can identify HER2+ tumors highly responsive to HER2-directed Tx
#TumorBoardTuesday

15/ 🔑 🔑 🔑 Points ‼️ #TumorBoardTuesday

⭐️ HER2 alterations occur in many cancers
⭐️ HER2/3 dimerization contributes to oncogenic activity & Tx resistance
⭐️ HER2 testing 🧪 recommended in many cancers; expression patterns vary
⭐️ IHC most commonly used; FISH = gold standard

16/ Thank you 🙏 for joining this #TumorBoardTuesday #Tweetorial! 
 
Take this knowledge on the go w/ 🆓 resources: integrityce.com/HER2resources

Don’t forget to pick up your #CME 👉 by answering 3 quick 🧠❓ 👇👇👇

17/ #Posttest Q 1⃣ #CME #TumorBoardTuesday

🤔 Which HER2 dimerization partner has been implicated in multiple mechanisms of Tx resistance ❓

Claim Credit: bit.ly/3rL0GOq

18/ #Posttest Q 2⃣ #CME #TumorBoardTuesday

🤔 Which drug conjugated to trastuzumab (ADC) has demonstrated an objective response rate of 40% in patients with hormone receptor➖, 🧬 HER2-low breast cancer ❓

Claim Credit: bit.ly/3rL0GOq

19/ #Posttest Q 3⃣ #CME #TumorBoardTuesday

🤔 What is the current gold 🪙 standard for 🧬 HER2 molecular testing ❓

Claim Credit: bit.ly/3rL0GOq