The first 60 days: BRCA or PALB2-mutant pancreatic ductal adenocarcinoma

Below, week by week, is what OnCo's record of BRCA or PALB2-mutant pancreatic ductal adenocarcinoma says about the first two months: the order is typical, the timing is yours to ask about. BRCA or PALB2-mutant pancreatic cancer is pancreatic cancer in someone who inherited a faulty copy of a gene that repairs broken DNA. These tumours respond better to platinum chemotherapy, and the POLO trial showed that the PARP inhibitor olaparib, taken after platinum has held the disease, delays its return; that made it the first targeted drug approved for a pancreatic cancer subgroup. Sections appear only where the record has something to say. Orientation, not medical advice.

Weeks 1 to 2

What happens now

Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.

Biomarkers your report may list

Germline BRCA1, BRCA2 and PALB2 testing in every patient at diagnosis Somatic homologous recombination gene alterations on tumour sequencing Homologous recombination deficiency signatures (investigational in the pancreas)Response to at least sixteen weeks of platinum without progression (POLO eligibility)BRCA reversion mutations in plasma at progression on a PARP inhibitor Family history and Ashkenazi Jewish ancestry (prior probability of a variant)

Ask which of these were tested and what the results were; see the report reader for what each value means.

Tests and imaging linked to this cancer

Germline (hereditary) testing Liquid biopsy (ctDNA)High-risk pancreatic surveillance (CAPS / PRECEDE)

Weeks 1 to 3

Who is on your team

These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.

A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.

Weeks 2 to 6

Decisions coming up

Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.

1.Resectable or borderline NCCN Guidelines: Pancreatic Adenocarcinoma
Platinum-based neoadjuvant or adjuvant chemotherapy (modified FOLFIRINOX) rather than gemcitabine alone; adjuvant PARP inhibition only in trials.
FOLFIRINOX / mFOLFIRINOX PRODIGE 24 / CCTG PA6 PREOPANC-1 Neoadjuvant / adjuvant / perioperative
2.Testing NCCN Guidelines: Pancreatic Adenocarcinoma
Germline testing for BRCA1, BRCA2, PALB2 and other cancer genes for every patient with pancreatic cancer, with cascade testing of relatives and surveillance for unaffected carriers in a research setting.
Germline (hereditary) testing Germline BRCA mutation (gBRCA)Germline vs somatic mutations High-risk pancreatic surveillance (CAPS / PRECEDE)
3.Metastatic, first line NCCN Guidelines: Pancreatic Adenocarcinoma
Platinum-containing chemotherapy: modified FOLFIRINOX, NALIRIFOX or gemcitabine plus cisplatin, chosen by fitness.
FOLFIRINOX / mFOLFIRINOX NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)Gemcitabine + cisplatin Cisplatin Platinum-sensitive / platinum-resistant
4.After progression on a PARP inhibitor NCCN Guidelines: Pancreatic Adenocarcinoma
Non-platinum chemotherapy (gemcitabine plus nab-paclitaxel) or daraxonrasib after first-line chemotherapy; trials of PARP inhibitor combinations.
Gemcitabine + nab-paclitaxel Daraxonrasib BRCA reversion mutations
5.Maintenance NCCN Guidelines: Pancreatic Adenocarcinoma
Olaparib after at least sixteen weeks of first-line platinum without progression in germline BRCA carriers (POLO); rucaparib for PALB2 and somatic alterations on phase 2 evidence; continued chemotherapy as the alternative.
Olaparib POLO Rucaparib PARP inhibitors

Every visit

Questions to ask at each visit

Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.

Newly diagnosed

What is my exact diagnosis, stage, and grade, and which tests established them?Everything else follows from an accurate stage and subtype.
Which biomarkers have been tested on my tumour (for example Germline BRCA1, BRCA2 and PALB2 testing in every patient at diagnosis, Somatic homologous recombination gene alterations on tumour sequencing, Homologous recombination deficiency signatures, Response to at least sixteen weeks of platinum without progression, BRCA reversion mutations in plasma at progression on a PARP inhibitor), and what were the results?These results decide eligibility for targeted therapy, immunotherapy, and trials.
Which subtype is my cancer, and does that change the recommended treatment?Recognised subtypes for this cancer include Germline BRCA2-mutant PDAC, Germline BRCA1-mutant PDAC, Germline PALB2-mutant PDAC.
Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.

Testing

For my situation (testing), which of the standard options do you recommend and why?Guideline options include: Germline testing for BRCA1, BRCA2, PALB2 and other cancer genes for every patient with pancreatic cancer, with cascade testing of relatives and surveillance for unaffected carriers in a research setting.

Metastatic, first line

For my situation (metastatic, first line), which of the standard options do you recommend and why?Guideline options include: Platinum-containing chemotherapy: modified FOLFIRINOX, NALIRIFOX or gemcitabine plus cisplatin, chosen by fitness.
Am I a candidate for FOLFIRINOX / mFOLFIRINOX, NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV), Gemcitabine + cisplatin or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Maintenance

For my situation (maintenance), which of the standard options do you recommend and why?Guideline options include: Olaparib after at least sixteen weeks of first-line platinum without progression in germline BRCA carriers (POLO); rucaparib for PALB2 and somatic alterations on phase 2 evidence; continued chemotherapy as the alternative.
Am I a candidate for Olaparib, Rucaparib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of POLO apply to someone like me?Trial populations differ from individual patients; ask how closely you match.

Resectable or borderline

For my situation (resectable or borderline), which of the standard options do you recommend and why?Guideline options include: Platinum-based neoadjuvant or adjuvant chemotherapy (modified FOLFIRINOX) rather than gemcitabine alone; adjuvant PARP inhibition only in trials.
Am I a candidate for FOLFIRINOX / mFOLFIRINOX, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
How do the results of PRODIGE 24 / CCTG PA6 and PREOPANC-1 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.

After progression on a PARP inhibitor

For my situation (after progression on a parp inhibitor), which of the standard options do you recommend and why?Guideline options include: Non-platinum chemotherapy (gemcitabine plus nab-paclitaxel) or daraxonrasib after first-line chemotherapy; trials of PARP inhibitor combinations.
Am I a candidate for Gemcitabine + nab-paclitaxel, Daraxonrasib, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.

Any stage

Are there clinical trials I could join, for example of Rucaparib, Niraparib, Talazoparib, Ipilimumab?Trials are how the next standard of care is set; asking early keeps options open.
Would a second opinion at a high-volume centre change anything, and can you help arrange it?Rare or high-stakes decisions benefit from a centre that treats many similar patients.
What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Supportive care improves quality of life and helps patients complete treatment.
I read that “Olaparib delays progression but has not lengthened overall survival, and the best duration of maintenance is unknown”. How does that affect my plan?Open problems are where trials and second opinions matter most.
I read that “Somatic and non-BRCA repair gene alterations respond unpredictably, and there is no validated homologous recombination deficiency test for the pancreas”. How does that affect my plan?Open problems are where trials and second opinions matter most.

Weeks 3 to 8

Trials to ask about

Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.

From day one

Help that costs nothing

Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.

Any time

What to read next

Words this page and the cancer page use

Familial pancreatic cancer and inherited risk (who qualifies for surveillance): Familial pancreatic cancer means at least two close relatives on the same side of the family have had the disease without a known gene fault to explain it.
Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026): In England the funded pancreatic cancer drugs are the older chemotherapies: FOLFIRINOX, gemcitabine with capecitabine, gemcitabine alone, and nab-paclitaxel with gemcitabine when other combinations are unsuitable.
BRCA reversion mutations: A cancer with a broken BRCA gene can repair the break itself under the pressure of PARP inhibitors or platinum: a second mutation restores the reading frame, the DNA-repair machinery switches back on, and both drugs stop working.
Platinum-sensitive / platinum-resistant: Whether a cancer that responded to platinum chemotherapy came back more than six months later (sensitive, so platinum can be used again) or sooner (resistant, so something else is needed).
Homologous recombination deficiency (HRD): A tumour that cannot properly repair double-strand DNA breaks, usually because of BRCA or related gene loss.
Germline BRCA mutation (gBRCA): An inherited fault in the BRCA1 or BRCA2 gene, present in every cell from birth, that greatly raises the risk of breast, ovarian, prostate and pancreatic cancer and makes those cancers sensitive to PARP inhibitors and platinum.
Germline vs somatic mutations: Germline mutations are inherited and in every cell; somatic mutations arise in the tumour only.
Drug resistance (primary and acquired): Why cancer drugs stop working: the tumour either never depended on the target or evolves around the block.
Neoadjuvant / adjuvant / perioperative: Neoadjuvant therapy is treatment given before surgery, adjuvant therapy is treatment given after it, and perioperative therapy is both.

Every term links to the glossary.