Incidence of Second Primary Malignancies in Patients with Neuroendocrine Tumours

Abstract

Background: An association between neuroendocrine tumours (NET) and increased risk of developing second primary malignancies (SPM) has been recognised. Methods: This was a retrospective review of our institutional prospectively maintained database of NET patients. We identified patients who had been diagnosed with both neuroendocrine and any additional malignancies via examination of patient notes. Results: Clinical data for 169 patients were analysed. After exclusion of patients known to have hereditary tumour predisposition syndromes, 29 SPM were identified in 26 patients (15.38%), the commonest being colorectal (n = 6), breast and renal carcinomas (both n = 5). SPM were classified as previous, synchronous or subsequent relative to NET diagnosis. Rates of SPM in pancreatic and small-bowel NET patients were comparable (15.7 vs. 19.6%, p = 0.78). A person-year methodology was used to compare observed numbers of SPM against expected values generated from age- and sex-specific incidence tables, with standardised incidence ratios (SIR) and 95% confidence intervals (CI) calculated. SPM incidence was significantly elevated in the synchronous subset (SIR 2.732, CI 1.177-5.382) whilst significantly fewer NET patients had a cancer history compared to the general population (SIR 0.4, CI 0.241-0.624). No overall differences were evident between observed and expected incidences of subsequent SPM (SIR 0.36, CI 0.044-1.051). The incidence of synchronous colorectal cancers was markedly elevated (SIR 13.079, CI 4.238-30.474). Conclusions: Our data support the use of colonoscopy in the diagnostic work-up of NET patients in anticipation of a colorectal SPM. The mechanistic underpinnings of this clinical phenomenon require further genetic investigation, and consideration of this knowledge in patient management pathways is warranted.

Co‐occurrence of breast cancer and neuroendocrine tumours: New genetic insights beyond Multiple Endocrine Neoplasia syndromes

“…Germline variants in MUTYH, CHEK2 and BRCA2 , well‐known breast cancer susceptibility genes were also identified in a whole‐genome sequencing study of 102 pancreatic NET patients . Although one recent SEER national database retrospective study showed an increased risk of pancreatic NET in patients with another first primary malignancy including female breast cancer, this was not found in other population studies …”

“…Recently, a SEER database retrospective study showed that the incidence of pancreatic NET is higher in patients with a first primary cancer of the pancreas, bladder, thymus and female breast cancer. However, multiple institutional cohort studies have reported a higher incidence of gastrointestinal and genitourinary second primary malignancies in patients with NETs and an Italian national database study of patients with a primary diagnosis of bronchopulmonary NET has shown a higher incidence of thyroid neoplasms in women and a higher incidence of kidney and bladder tumours in men. Importantly, these studies did not show a higher incidence of breast cancer in NET patients.…”

Primary small intestinal neuroendocrine tumors are highly prevalent and often multiple before metastatic disease develops

“…Further studies would be warranted to elucidate this transformation in SI-nET occurrence. Also, since there is a high rate of synchronous malignancies in the presence of clinical SI-nET (14)(15)(16), the frequency of other malignancies in patients with SI-nET at autopsy was scrutinized.…”

Neuroendokrine Tumoren in der täglichen gastroenterologischen und endoskopischen Praxis – ein klinisch orientierter Leitfaden

“…Bei bis zu 20 % der Patienten mit NET werden syn-und metachrone Neoplasien anderer Entitäten wie gastrointestinale Adenokarzinome oder Mammakarzinome diagnostiziert [14,15]. Zudem ist eine Vielzahl von genetischen Syndromen, etwa das multiple endokrine Neoplasie-Syndrom Typ 1 (MEN1), das von Hippel-Lindau-Syndrom und die Neurofibromatose Typ 1, mit pankreatischen NET assoziiert [13].…”