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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.
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.
Local 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.
For 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.
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.
Site decides cause and behaviour: HPV drives oropharyngeal cancer, EBV drives nasopharyngeal cancer, tobacco drives oral and laryngeal cancer; all drain into the neck node levels that surgeons and radiotherapists map.
Same organ: Acinic cell carcinoma of the salivary glands, Carcinoma ex pleomorphic adenoma, Multiple endocrine neoplasia type 1 (MEN1), Multiple endocrine neoplasia type 2 (MEN2A and MEN2B), Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma), Oropharyngeal cancer (tonsil and base of tongue), Laryngeal and hypopharyngeal cancer, Oral cavity cancer (mouth and tongue), Head and neck squamous cell carcinoma, Nasopharyngeal carcinoma, Salivary gland cancers, Papillary thyroid cancer, Follicular thyroid cancer, Medullary thyroid cancer, Anaplastic thyroid cancer, Thyroid cancer, Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma), NUT carcinoma (midline carcinoma with NUTM1 rearrangement), Parathyroid carcinoma, Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4), HPV-positive oropharyngeal cancer, HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, Hypopharyngeal cancer, Adenoid cystic carcinoma, Mucoepidermoid carcinoma, Oral tongue and floor of mouth cancer, Buccal mucosa and gingivobuccal cancer (oral cancer in India), Lip cancer, Locoregionally advanced nasopharyngeal carcinoma (stage III to IVA), Recurrent and metastatic nasopharyngeal carcinoma, Esthesioneuroblastoma (olfactory neuroblastoma), Sinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma
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.
Trastuzumab with docetaxel (phase 2, response rate 70 percent); trastuzumab deruxtecan on progression or as an alternative.
Androgen deprivation with leuprorelin and bicalutamide; enzalutamide or apalutamide as alternatives or after progression.
Platinum-based chemotherapy (carboplatin-paclitaxel or cisplatin-based); pembrolizumab for PD-L1-positive, mutation-rich or mismatch repair-deficient tumours.
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HER2 testing is standard in salivary duct carcinoma and trastuzumab-docetaxel a first-line option for HER2-positive advanced disease, with trastuzumab deruxtecan available at progression.
Androgen receptor testing and androgen deprivation therapy are now standard options for salivary duct carcinoma, often before chemotherapy in slowly progressing disease.
The observation-first approach for indolent metastases and the move to biomarker-directed therapy (HER2, androgen receptor, NTRK) on the salivary cancer pages follow this review's conclusions.
Cisplatin chemoradiation after surgery is standard for extranodal extension or involved margins; radiotherapy alone suffices for other adverse features.
Query for this cancer: (TITLE:"Salivary duct carcinoma" OR ABSTRACT:"Salivary duct carcinoma" OR TITLE:"SDC" OR ABSTRACT:"SDC" OR TITLE:"High-grade salivary duct carcinoma" OR ABSTRACT:"High-grade salivary duct carcinoma" OR TITLE:"Androgen receptor-positive salivary carcinoma" OR ABSTRACT:"Androgen receptor-positive salivary carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Salivary duct carcinoma, not a curated reading list.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
A swollen painful calf, or sudden breathlessness with chest pain; the tamoxifen boxed warning covers pulmonary embolism and stroke.
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
Any new or worsening cough, breathlessness or fever. The label says to interrupt treatment for any suspected ILD and to permanently discontinue for grade 2 or higher.
Temperature of 38 C or higher, or feeling shivery and unwell even without a fever. Antibody-drug conjugates suppress the bone marrow, and several carry a boxed warning for severe neutropenia.
CYP3A4: Enzalutamide (strong inducer) lowers Apalutamide exposure and may cause loss of efficacy.. Avoid strong inducers; if unavoidable, consider a dose increase per label and monitor response.
See all on the product pages:ApalutamideBicalutamideCarboplatinCisplatinDocetaxelEnzalutamideLeuprolide (leuprorelin) and GnRH agonistsPaclitaxel / nab-paclitaxelPembrolizumabTrastuzumab deruxtecan·Printable cards in the navigator
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