Teaching pack: Mucinous ovarian cancer

Primary mucinous carcinoma of the ovary is uncommon and was historically over-diagnosed because metastases from the appendix, colon, stomach and pancreas mimic it. True primary tumours carry KRAS mutations in about two thirds and HER2 amplification in a fifth, share their biology with gastrointestinal cancers and often arise from a mucinous borderline tumour. Most are stage I and treated with surgery alone or with fertility-sparing unilateral oophorectomy; appendicectomy is performed if the appendix looks abnormal. Advanced disease responds poorly to carboplatin-paclitaxel, and gastrointestinal-type regimens such as capecitabine-oxaliplatin are used by extrapolation; HER2-directed therapy is an option in amplified tumours.

• Strict pathology criteria have cut the diagnosis to its true rare frequency and improved apparent survival.
• The GI-like biology is steering treatment toward bowel cancer regimens and HER2-directed therapy.
• International rare-tumour trials (mEOC/GOG 241) showed how hard it is to recruit for this disease.

1. 2003Seidman shows most 'mucinous ovarian cancers' are metastases from the gut
2. 2019mEOC/GOG 241 randomised trial closes early for poor accrual
3. 2020WHO classification separates expansile from infiltrative mucinous carcinoma

• Trastuzumab deruxtecan (treatment)
• HER2 (target)

• No proven chemotherapy for advanced disease.
• Trials cannot recruit enough patients.
• Distinguishing primary from metastatic disease still needs expert pathology.

1. What does 'triple-negative' mean in breast cancer?
   Answer

   The tumour lacks the three receptors other breast cancers can be treated through: oestrogen receptor, progesterone receptor, and HER2 (IHC 0-1+ or 2+/ISH-negative).
2. Why does trastuzumab deruxtecan work in 'HER2-low' breast cancers that older HER2 drugs ignored?
   Answer

   Its cleavable linker releases a membrane-permeable topoisomerase-I payload (DXd) at high DAR, so a small amount of HER2 is enough to deliver drug and the payload diffuses to kill neighbouring cells (bystander effect); HER2-low is a delivery address, not a driver. DESTINY-Breast04 and -06 proved it.
3. In what setting did T-DXd move into early-stage HER2-positive breast cancer in 2026?
   Answer

   Neoadjuvant (DESTINY-Breast11, T-DXd followed by THP, pCR 67.3% vs 56.3%) and post-neoadjuvant residual disease (DESTINY-Breast05, beating T-DM1), both approved Q2 2026.
4. What is the bystander effect in ADCs?
   Answer

   A released, membrane-permeable payload diffuses out of the targeted cell and kills neighbouring cells that lack the antigen; requires a cleavable linker and permeable payload (DXd, MMAE, SN-38), explaining T-DXd's activity in HER2-low disease and T-DM1's lack of it.
5. What should I ask before starting an ADC such as Enhertu?
   Answer

   How lung inflammation (ILD) will be monitored and what symptoms to report immediately; HER2 status and how it was scored; expected nausea, hair loss, and blood counts; dosing schedule (every three weeks); how response will be assessed and when; what comes next if it stops working.
6. Who should have germline genetic testing when diagnosed with cancer?
   Answer

   All patients with TNBC, ovarian, pancreatic, or metastatic prostate cancer, increasingly all breast cancer, and anyone with suggestive family history; results change surgery, drug choice (PARP inhibitors), and family screening.

• Wikipedia: https://en.wikipedia.org/wiki/Ovarian_cancer
• Wikipedia: https://en.wikipedia.org/wiki/Ovarian_cancer