ECE2023 Poster Presentations Endocrine-related Cancer (62 abstracts)
Increased frequency of breast cancer in young Carney Complex patients suggests a role for inactivation of the tumor suppressor gene PRKAR1A
Patricia Vaduva 1 , Florian Violon 1 , Anne Anne Jouinot 1,2 , Lucas Bouys 1,2 , Stéphanie Espiard 3 , Fidéline Bonnet 1 , Marie-Odile North 4 , Cardot Catherine 3 , Gerald Raverot 5 , Hieronimus Sylvie 6 , Hervé Lefebvre 7 , Marie-Laure Nunes 8 , Antoine Tabarin 8 , Lionel Groussin 2 , Guillaume Assié 2 , Mathilde Sibony 9 , Marie Christine Vantyghem 3 , Eric Pasmant 4 & Jerome Bertherat 1,2
1Cochin, Genomics and Signaling of Neuroendocrine Tumors, Paris, France; 2Cochin Hospital, Endocrinology, Paris, France; 3Lille University Hospital, Department of Endocrinology, Diabetology, Metabolism and Nutrition, Lille, France; 4Cochin Hospital, Oncogenetics, Paris, France; 5Hospices Civils de Lyon, Groupement Hospitalier Est, Endocrinology, Bron, France; 6Nice University Hospital, Endocrinology, Diabetology, Reproductive medicine, Nice, France; 7Univ Rouen Normandie, INSERM, NORDIC UMR 1239, CHU Rouen, Endocrinology, Rouen, France; 8Bordeaux University Hospital, Department of Endocrinology, Diabetology and Metabolism, Pessac, France; 9Cochin Hospital, Pathology, Paris, France
Objective: Carney Complex (CNC) is a rare hereditary genetic syndrome, mostly due to inactivating pathogenic variants of the tumor suppressor gene PRKAR1A. It has a wide spectrum of manifestations with frequent pigmented skin lesions, cardiac myxomas, primary pigmented nodular adrenocortical dysplasia, acromegaly and thyroid cancers. Breast benign tumors (fibroadenomas, ductal adenomas and myxoid lesions) have been associated with CNC, but so far, association with malignancy has not been investigated.
Methods: The present study was designed to describe the characteristics of breast tumors diagnosed in CNC patients and their association with other manifestations of CNC and PRKAR1A genotype. Since breast cancer is the most frequent cancer in women, malignant breast lesions were carefully analyzed. This cohort comes from a 3 years’ follow-up multicenter French prospective study of CNC patients (Espiard, JCEM 2020). The 50 included women were investigated for CNC manifestations and particularly breast tumors, with breast echography, genetic and hormonal investigations, in order to characterize them and assess the frequency and average age of breast cancer.
Results: Among the 38 women with breast imaging, 14 had breast tumors (50% bilateral). Ten women (20%) presented with benign tumors. Six women presented (12%) with breast carcinomas: five had invasive cancer under 50 years of age (4 ductal adenocarcinomas and one solid intracystic papillary carcinoma) and one had ductal carcinoma in situ. The occurrence of breast cancer was more frequent in the CNC women with PRKAR1A pathogenic variants than in the general population (OR=6.2[1.58-17.31]; P=0.006). The mean age at breast cancer diagnosis was 44.7 years old, 17 years younger than in the general population. Cumulative risk of developing breast cancer in our cohort was higher if compared to French women under 40 (OR=30.25[6.06-93.06]; P=1,67-4) or 50 years old (OR=116,90[19,14-1246,78]; P=8,17-8). Breast cancer had good prognosis factors: 5 out of 6 tumors were T1N0M0. One woman had metastatic breast cancer, alive after 15 years follow up. All breast cancers were negative for HER2, with positivity for estrogen receptor(100%) and progesterone receptor(50%). They all occurred in individuals with familial CNC and PRKAR1A pathogenic variants. Loss of heterozygosity at the PRKAR1A locus observed in 2 investigated breast carcinomas tissues suggests that PRKAR1A bi-allelic inactivation could promote breast cancer development.
Conclusions: Breast carcinoma occurs frequently and prematurely in women with CNC, suggesting that CNC predisposes to breast carcinoma. This suggests that adequate screening strategy (starting around 40 years old) and follow up should be discussed in CNC women.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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