{"entity":{"id":"salivary-duct-carcinoma","kind":"cancer","name":"Salivary duct carcinoma","aka":["SDC","High-grade salivary duct carcinoma","Androgen receptor-positive salivary carcinoma"],"tldr":"Salivary duct carcinoma is an aggressive cancer of the parotid gland that behaves like a high-grade breast cancer and carries the same switches: most tumours run on the androgen receptor and about a third on HER2, so hormone blockers borrowed from prostate cancer and trastuzumab borrowed from breast cancer now shrink many of them.","summary":"Salivary duct carcinoma is a high-grade adenocarcinoma of the salivary ducts, usually of the parotid gland in men over sixty, that under the microscope looks like high-grade ductal carcinoma of the breast with comedo necrosis, and sometimes arises within a long-standing pleomorphic adenoma. It spreads early to the neck nodes and to lung and bone, and facial nerve palsy at presentation is common. The great majority of tumours express the androgen receptor, about a third have HER2 amplification, and TP53, PIK3CA and HRAS mutations are frequent, so molecular profiling at diagnosis is standard.\n\nLocal treatment is parotidectomy with sacrifice of the facial nerve when it is involved, neck dissection and postoperative radiotherapy or chemoradiation, but most patients relapse at a distance, and systemic treatment borrowed from breast and prostate cancer is what has changed the disease. For HER2-positive tumours a Japanese phase 2 of trastuzumab with docetaxel in 57 patients produced responses in 70.2 percent with median progression-free survival of 8.9 months and median overall survival of 39.7 months, and trastuzumab deruxtecan and trastuzumab emtansine have produced responses in HER2-positive salivary cancers in tumour-agnostic studies.\n\nFor androgen receptor-positive disease, a phase 2 of leuprorelin with bicalutamide in 36 patients produced responses in 41.7 percent with median progression-free survival of 8.8 months, and the EORTC 1206 trial randomised androgen deprivation against chemotherapy; enzalutamide gave more modest responses in a phase 2, and apalutamide with a GnRH agonist is in trial. Patients whose tumours have both markers may be treated sequentially, and combined anti-HER2 and anti-androgen treatment is being explored; platinum-based chemotherapy and pembrolizumab for the rare PD-L1-high or mutation-rich tumour are the remaining options.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Salivary_duct_carcinoma","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Salivary_duct_carcinoma"}],"tags":["subtype-page","head-and-neck"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-bernier-eortc-22931-nejm-2004","paper-laurie-licitra-salivary-systemic-jco-2006","paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019","paper-fushimi-androgen-deprivation-salivary-duct-ann-oncol-2018"],"journals":[],"dependsOn":[],"notes":[],"group":"head and neck","burden":"A rare, aggressive salivary cancer that resembles high-grade breast ductal carcinoma, mostly in older men and mostly in the parotid; the great majority express the androgen receptor and about a third overexpress HER2, which has made it the most drug-targetable salivary cancer.","subtypes":["Salivary duct carcinoma of the parotid (the great majority)","HER2-amplified salivary duct carcinoma (about a third)","Androgen receptor-positive, HER2-negative salivary duct carcinoma","Salivary duct carcinoma arising in a pleomorphic adenoma (carcinoma ex pleomorphic adenoma)","Micropapillary and sarcomatoid variants"],"biomarkers":["Androgen receptor immunohistochemistry","HER2 immunohistochemistry and in situ hybridisation","TP53, PIK3CA and HRAS mutations","PD-L1 and tumour mutational burden (usually low)","Extranodal extension and margin status"],"standardOfCare":[{"setting":"Localised, resectable","approach":"Total parotidectomy (or resection of the affected gland) with facial nerve sacrifice where involved, neck dissection and postoperative radiotherapy, with cisplatin for extranodal extension or positive margins.","refs":["imrt-igrt","cisplatin","chemoradiation"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"HER2-positive recurrent or metastatic","approach":"Trastuzumab with docetaxel (phase 2, response rate 70 percent); trastuzumab deruxtecan on progression or as an alternative.","refs":["trastuzumab","docetaxel","trastuzumab-deruxtecan","her2"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Androgen receptor-positive recurrent or metastatic","approach":"Androgen deprivation with leuprorelin and bicalutamide; enzalutamide or apalutamide as alternatives or after progression.","refs":["leuprolide","bicalutamide","enzalutamide","apalutamide","androgen-deprivation","nct04325828"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}},{"setting":"Marker-negative or after targeted treatment","approach":"Platinum-based chemotherapy (carboplatin-paclitaxel or cisplatin-based); pembrolizumab for PD-L1-positive, mutation-rich or mismatch repair-deficient tumours.","refs":["cisplatin","carboplatin","paclitaxel","pembrolizumab"],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: Head and Neck Cancers","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1437"}}],"stateOfArt":["Routine HER2 and androgen receptor testing has turned a uniformly lethal tumour into one with two lines of targeted therapy.","Trastuzumab-docetaxel and androgen deprivation give responses in a majority and a large minority respectively, though relapse remains the rule.","Antibody-drug conjugates against HER2 are the next step, following their success in breast and gastric cancer."],"history":[{"year":1968,"title":"Kleinsasser describes salivary duct carcinoma as a breast-like tumour of the parotid","refs":[]},{"year":2018,"title":"Leuprorelin with bicalutamide: phase 2 response rate 41.7 percent","refs":["leuprolide","bicalutamide"]},{"year":2019,"title":"Trastuzumab with docetaxel: phase 2 response rate 70.2 percent","refs":["trastuzumab","docetaxel"]},{"year":2020,"title":"Apalutamide with a GnRH agonist enters trial for androgen receptor-positive salivary cancer","refs":["nct04325828"]}],"pipeline":["trastuzumab-deruxtecan","apalutamide","nct04325828","enzalutamide"],"openProblems":["Almost all responses to targeted treatment are followed by relapse.","Whether to give anti-HER2 or anti-androgen treatment first when both targets are present.","No randomised trial has compared targeted treatment with chemotherapy except EORTC 1206.","Adjuvant targeted treatment after surgery is untested."],"parent":"salivary-gland"},"route":"/cancers/salivary-duct-carcinoma/","neighbours":{"paper":[{"id":"paper-fushimi-androgen-deprivation-salivary-duct-ann-oncol-2018","kind":"paper","name":"Combined androgen blockade in androgen receptor-positive salivary gland carcinoma","route":"/key-papers/paper-fushimi-androgen-deprivation-salivary-duct-ann-oncol-2018/"},{"id":"paper-bernier-eortc-22931-nejm-2004","kind":"paper","name":"EORTC 22931: postoperative irradiation with or without concomitant cisplatin for locally advanced head and neck cancer","route":"/key-papers/paper-bernier-eortc-22931-nejm-2004/"},{"id":"paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019","kind":"paper","name":"Phase 2 trial of trastuzumab and docetaxel in HER2-positive salivary duct carcinoma","route":"/key-papers/paper-takahashi-trastuzumab-docetaxel-salivary-duct-jco-2019/"},{"id":"paper-laurie-licitra-salivary-systemic-jco-2006","kind":"paper","name":"Systemic therapy in the palliative management of advanced salivary gland cancers (review)","route":"/key-papers/paper-laurie-licitra-salivary-systemic-jco-2006/"}],"drug":[{"id":"apalutamide","kind":"drug","name":"Apalutamide","route":"/drugs/apalutamide/"},{"id":"bicalutamide","kind":"drug","name":"Bicalutamide","route":"/drugs/bicalutamide/"},{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"docetaxel","kind":"drug","name":"Docetaxel","route":"/drugs/docetaxel/"},{"id":"enzalutamide","kind":"drug","name":"Enzalutamide","route":"/drugs/enzalutamide/"},{"id":"leuprolide","kind":"drug","name":"Leuprolide (leuprorelin) and GnRH agonists","route":"/drugs/leuprolide/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"trastuzumab","kind":"drug","name":"Trastuzumab","route":"/drugs/trastuzumab/"},{"id":"trastuzumab-deruxtecan","kind":"drug","name":"Trastuzumab deruxtecan","route":"/drugs/trastuzumab-deruxtecan/"}],"trial":[{"id":"nct04325828","kind":"trial","name":"A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma","route":"/trials/nct04325828/"}],"technology":[{"id":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"extranodal-extension","kind":"term","name":"Extranodal extension (ENE)","route":"/terms/extranodal-extension/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"cancer":[{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"}]}}