Germline BRCA2 variants in advanced pancreatic acinar cell carcinoma: A case report and review of literature

Table 2 Germline and somatic molecular profiles of the pancreatic ductal adenocarcinoma patients in this study

Year of diagnosis	Age at diagnosis	Germline testing	Somatic testing	Driver mutation	Personal or family history of malignancy	Disease staging	Surgery and perioperative chemotherapy	TTP after surgery (mo)	First line systemic therapy	Second line systemic therapy	Best treatment and clinical status	OS (mo)
2014	65	BRCA1, BRCA2 negative	Not performed	Nil	Family history of leukemia, colorectal, ovarian, and prostate cancers	T3N0M0 R1	Neoadjuvant mFFX with radiotherapy followed by Whipple procedure	1.5	Gemcitabine for 4 cycles	BSC	PD, DOD	28.2
			MMR IHC intact
2014	63	Not performed	Not performed	Nil	Nil	T3N1bM0 R0	Whipple procedure with perioperative mFFX for 12 cycles	10.4	BSC	Nil	PD, DOD	23.2
2014	74	CDKN2A pathogenic variant c.159G>C, p.Met53Ile	Not performed	Nil	Family history of melanoma and PDAC	Stage IV	Nil	NA	mFFX for 3 cycles	BSC	PD, DOD	4.6
					Personal history of malignant melanoma
2015	60	Not performed	Not performed	Nil	Thoracic cancer	T2N0M0 R0	Distal pancreatectomy with adjuvant Gemcitabine for 2 cycles which were discontinued due to toxicities	10.7	GnP 18 mo	N/A	SD, DOD	36.0
2017	66	WGS and RNA seq	WGS and RNA seq	KRAS, SMAD4	Nil	Stage IV	Nil	NA	mFFX for 8 cycles	BSC	SD, DOD	13.4
			KRAS, SMAD4, CDKN2A TP53, ATM, TGFBR2, and KDM6A
			MMR IHC intact
2018	64	Not performed	Not performed	Nil	Nil	T3N0M0 R0	Whipple procedure. No adjuvant therapy	10.6	GnP for 4 cycles	BSC	PD, DOD	32.3
2020	61	91 gene panel	WGS and RNA seq	BRAF	Family history of PDAC	Stage IV	Nil	NA	GnP for 16 cycles	Cobimetinib 60 mg OD PO (enrolled on CAPTUR trial	PR, AWD	20.4 ongoing
			SND1-BRAF fusion
			MMR IHC intact
2021	70 (case described)	12 gene panel	Not performed	BRCA2	Family history of ovarian cancer	Stage IV	Nil	NA	mFFX for 11 cycles	Maintenance Olaparib 150 mg twice daily	PR, AWD	11.5 ongoing
		BRCA2
		Likely pathogenic variant
		c.4356delinsCA, p.Gln1452Hisfs*8	MMR IHC intact		Personal history of renal cell cancer and NSCLA
2021	65	91 gene panel	Not performed	Nil	Family history of head and neck cancer	Stage IV	Nil	NA	mFFX for 14 cycles, followed by maintenance FOLFIRI	RP-3500 in combination with Gemcitabine (enrolled on RP-3500-01 trial)	SD, ADW	13.4 ongoing
		ATM
		Pathogenic variant
		c.8418+5_8418+8del
2021	71	BRCA1, BRCA 2	Not performed	BRCA2	Family history of breast cancers	Stage IV	Nil	NA	5FU with Oxaliplatin for 12 cycles, downsized to Whipple procedure	N/A	PR, AWD	12.1 ongoing
		BRCA2 pathogenic variant c.8904delC, p.Val2969Cysfs*7
2021	57	12 gene panel negative	Not performed	Nil	Family history of non-Hodgkins Lymphoma	Stage IV	Nil	NA	Ongoing mFFX; had 16 cycles	N/A	PR, AWD	12.3 ongoing

TTP: Time to progression; OS: Overall survival; MMR IHC: Mismatch repair immunohistochemistry; mFFX: Modified FOLFIRINOX; GnP: Gemcitabine with Nab-paclitaxel; BSC: Best supportive care; PD: Progressive disease; DOD: Dead of disease; SD: Stable disease; PR: Partial response; AWD: Alive with the disease; WGS: Whole genome sequencing; RNA seq: RNA sequencing; PDAC: Pancreatic ductal adenocarcinoma; NSCLA: Non-small cell lung adenocarcinoma.