THU504 Is Carney Complex A Predisposing Syndrome For Breast Cancer? Prospective Study Of 50 Women
Authors: Vaduva Patricia , Violon Florian , Jouinot Anne , Bouys Lucas , Espiard Stéphanie , Bonnet-Serrano Fidéline , Odile North Marie , Cardot-Bauters Catherine , Raverot Gerald , Hieronimus Sylvie , Lefebvre Herve , Nunes Marie Laure , Tabarin Antoine , Rouiller Lionel Groussin , Assié Guillaume , Sibony Mathilde , Vantyghem Marie-Christine , Eric Pasmant , Bertherat Jerome 
Published: October 2023

Disclosure: P. Vaduva: None. F. Violon: None. A. Jouinot: None. L. Bouys: None. S. Espiard: None. F. Bonnet-Serrano: None. N. Marie Odile: None. C. Cardot-bauters: None. G. Raverot: None. S. Hieronimus: None. H. Lefebvre: None. M.L. Nunes: None. A. Tabarin: None. L. Groussin Rouiller: None. G. Assié: None. M. Sibony: None. M. Vantyghem: None. P. Eric: None. J. Bertherat: None.

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 (PPNAD) causing Cushing syndrome, 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 and the leading cause of death from cancer worldwide, 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 imaging (echography+/-mammography), 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 (28%) had breast tumors, half of them being bilateral. Ten women (20%) presented with benign tumors. Six women presented (12%) with breast carcinomas: five had invasive cancer under 50 years of age (10%) with one contralateral recurrence (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[1.6-17.3]; 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 breast cancer for women under 40 years of age was much higher in CNC women, compared to women worldwide (OR=592.1[79.7-3817.4]; p=9.58). Breast cancer had good prognosis factors: 5 out of 6 tumors were T1N0M0, so stage I. One woman had metastatic breast cancer, still alive after 15 years follow up. All breast cancers were negative for HER2, with 100% positivity for estrogen receptor and 50% for progesterone receptor. 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 tumor tissue suggests that PRKAR1A bi-allelic inactivation could promote breast cancer development. Conclusions: Breast carcinoma occurs frequently and at an early age 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.

Presentation: Thursday, June 15, 2023