🚨 The Clinical Genetics Service at Memorial Sloan Kettering Cancer Center is hosting a patient symposium focusing on #ATM & #PALB2 🧬

🗓️ 11/14
⌚️6:30 PM ET
📍Zoom

All are cordially invited. Please share with your colleagues & patients!

Register: meetmsk.zoom.us/webinar/regist…

Follow ACMG throughout October as we recognize #BreastCancerAwarenessMonth and share resources and current information on #genetic and #genomic testing and clinical management of patients at increased risk of #breastcancer . #brca #PALB2 #hereditarycancer #publichealth

Using a strategy combining both monogenic and polygenic approaches, researchers achieved a better identification of high-risk #BreastCancer patients in a large retrospective study bit.ly/49fTyM2 Alexandre Bolze Joe Grzymski #GIMO #PopulationScreening #BRCA1 #BRCA2 #PALB2 #ATM

🎙Score genomic 🔄 local failure for #brainmetastase
📌570 👥w/1,487 BM➡️WBRT OR SRS
OncoPanel for all 👥
👉11 genes (ATM, MYCL, PALB2, FAS, PRDM1, PAX5, CDKN1B, EZH2, NBN, DIS3, MDM4) 🔄⬇️LF
👉2 genes (FBXW7 & AURKA) 🔄⬆️LF
👉Brain-RPS developed w/ genes
👉RPS🔄LF in MVA

🧬Can genetics be used to delay mammogram screening?
JAMA Oncology

➡️Retrospective case-control study, 25 591 women
➡️Low-risk genetic group: absence of pathogenic variants or VUS in BRCA1, BRCA2, PALB2, ATM, or CHEK2, and a low polygenic risk score (bottom 10%)
➡️9.1% low risk,…

Interesting approach! Teaching an old drug new tricks, Sagar Sardesai presents data for omeprazole as adjunct therapy in TNBC, leading to reduction in FASN expression and activity with promising pCR of 72.4%. Next step combo with PARPi in BRCA1/2mut and PALB2?

#DAVAHawaiiBreast

After neoadjuvant talazoparib results in BRCAm BC (Litton J.K. 2017), neoadjuvant olaparib in #ovariancancer (with mutation in BRCA1/2, RAD51C/D, or PALB2) by Shannon Westin, MD, MPH, FASCO shows outstanding surgical outcomes after only 2 cycles of olaparib, even in Stage IV pts #SGOMTG #SGO2023

Breast cancer predisposition genes

BARD1, CHEK2 = Breast ca alone ('BARe CHEst')
CDH1 = Chest & DH1gestive (i.e. gastric)
ptEN = ENdometrial
STK11 = STinKy cancer (colorectal)
PALB2 = PAncreatic & Breast
ATm = pancreATic & breAsT
BRca & BRip1 = BReast ca

#GeneChat #oncology

🧬Germline pathogenic variants and breast cancer
JAMA Oncology

Interval-detected (IC) vs screen-detected cancer (SDC)

✅Another example of how genetics may affect population screening in future

➡️Pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 genes were more common…

✅NAPOLI-3 - positive study in PDAC which has to be 👏, but unlikely to replace std FFX, HR 0.83 for OS, p=0.04
➡️ PASS-01 trial evaluating mFFX vs GnP but excluding gBRCA1/2 & PALB2

APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6 ve PALB2 genlerindeki kalıtsal patojenik mutasyonların mide kanseriyle ilişkili olduğu bulundu. Bu varyantlar, iki benzer veya aynı DNA molekülü arasında nükleotid dizisi değişimiyle ilgili olan homolog rekombinasyon ile ilişkilidir.

Today’s #trialtuesday is led by Alok Tewari of Dana-Farber Lank Center for Genitourinary Oncology. #CCTI_DFCI presents Trial 23-643: USP1 inhibitor for BRCA 1/2, PALB2, RAD51C/D mutated or HSD positive solid tumors. Now in dose escalation. @DanaFarber Dana-Farber News
Visit: forms.office.com/r/kM7e6JVxre

Parp inhibitors in mCRPC. Indivisual genes pooled analysis by @usfda published in Journal of Clinical Oncology .
Something that we know beforehand.
Parp inhibitors work best in BRCA 1 and BRCA 2 mutations , CDK12 mutations ( and PALB2 mutations small numbers in trial )
They DO NOT work in…

ข้อสังเกตอื่น
1. สัดส่วนของผู้พบการกลายพันธุ์ราว 2-4.5% อายุน้อยมีโอกาสเจอมากกว่า
2. ผู้ที่มี APC, CDH1 mutations มีโอกาสเกิดโรคเร็วกว่ายีนอื่น
3. ลำดับความเสี่ยงจากมากไปหาน้อย: MLH1, APC, CDH1 ที่เหลือไล่เลี่ยกัน (BRCA1, BRCA2, PALB2, ATM, MSH2, MSH6)

Interestingly, women carrying germline pathogenic variants in ATM, BRCA, BRCA2, CHEK2, and PALB2 have an increased risk of #breastcancer and may benefit from improved surveillance and risk reduction strategies.
ascopubs.org/doi/full/10.12…

TALAPRO-2 Cohort 2 (HRRm) analysis: Enza+/-talazoparib
🔷rPFS: HR=0.45 (0.33-0.61)
🔷rPFS in BRCA1/2: HR=0.20 (0.11-0.36). No benefit in other gene clusters (ATM, CDK12, PALB2)
🔷OS (24% maturity): HR=0.69 (0.46-1.03)
🔷Gr3+ AEs: 66% vs 37% (Anemia: 40% vs 16%)
UroToday.com #ASCO23

Does germline promoter methylation in BRCA1/2 and PALB2 explain the missing heritability in women with strong family history who test negative? The results of germline methylation testing thus far suggest that it is not a major contributor- Dr. Ian Campbell at #BRCA symposium

อ้าว กำ .. CX-5461 (Pidnarulex) ยามะเร็งตัวใหม่ที่ใช้กลไก synthetic lethality เหมาะกับผู้ป่วยมะเร็งที่มี BRCA1/2 หรือ PALB2 mutations ตอนนี้กำลังทำ phase 1/2 clinical trial อยู่ มีงานตีพิมพ์ใน Nature Genetics ว่ายาตัวนี้เป็น potent mutagen ในเซลล์ปกติด้วย
nature.com/articles/s4158…

IPARP: exclusively for BRCA?
US FDA pooled analysis,
✅BRCA1(n=64),PFSHR 0.51,OSHR 0.74
✅BRCA2(n=422), 0.31 and 0.66
✅CDK12(n=164), 0.50 and 0.63
✅PALB2(n=41),0.52 and 0.78
⭕️ATM(n=268), 1.05 and 1.18
⭕️CHEK2(n=172), 1.06 and 1.53
doi: 10.1200/JCO.23.02105

BRCA2 plays an essential role in DNA repair through homologous recombination. The promotion of homologous recombination by BRCA2 requires its interaction with a second protein, the partner and localizer of BRCA2 (PALB2).

Schematic from frontiersin.org/journals/oncol…