Abstract P3-10-07: Uptake of risk reducing measures in healthy BRCA 1-2 mutation carriers from Northern Italy: Outcomes of 9 years of close-surveillance. Experience of the hereditary cancer clinic in the region of Veneto, Italy
Authors: Rastelli A , Azzolin F , Tognazzo S , Alducci E , Zovato S 
Published: February 2018

Background: There are several options for cancer reduction in women with a BRCA 1-2 mutation, including prophylactic surgery, chemo-prevention and close surveillance. Each of these measures offers varying levels of effectiveness with prophylactic mastectomy (PM) and oophorectomy (PO) providing the greatest risk reduction for the development of breast and ovarian cancer. The uptake of preventive procedures, however, differs according to country, not only in relation to access to care, but also cultural preferences. Here we present data on the experience of the Hereditary Cancer Center at the Istituto Oncologico Veneto, which is one of the few centers in Northern Italy to offer not only genetic testing, but also long-term follow-up to healthy carriers of the BRCA 1-2 genes. Methods: 106 healthy women were identified within a cohort of BRCA positive individuals followed since 2008. Upon learning of their BRCA mutation carrier status, they all agreed to enroll in a long-term protocol of close-surveillance. All women were also informed about risk-reducing surgery such as PO and PM. Results: The age in this sample ranged between 20 and 77 years with a median of 41.5. The average follow-up time was 4.3 +/-2.4 years. We observed that PO was more commonly accepted (41% 44/106) than PM (11% 12/106). The mean age at the time of PO was 47.3. In the PM group, half of the women decided to undergo such procedure only after being diagnosed with breast cancer. The mean age at the time of PM in the healthy subjects was 41.8 years.

Over the follow-up period, 9.4% of the patients (10/106) developed BRCA related malignancies, of which 9 breast and 1 ovarian cancer. Of the 9 breast events, 2 were diagnosed at stage 0, 2 at stage I, 3 at stage II, and 2 at stage III. All cancer cells were aggressive (grade 3). Of the 2 stage III breast tumors, 1 was diagnosed on the very 1st breast MRI screening, and the other after an interval of 3 years due to the patient being pregnant and then breastfeeding. The 3 cases of stage II breast cancer, despite being 1 cm or less in size, already had node involvement. Both stage III breast tumors were triple negative in BRCA 1 carriers. The other breast cancers were ER+ and none was Her2+. Of the ER+ breast events 4 occurred in BRCA2 and 2 in BRCA1 carriers. Except for the 2 Stage 0 tumors, which arose in women who had a previous oophorectomy, all the other breast malignancies developed in carriers who still had their ovaries and were premenopausal. The one serous ovarian cancer was diagnosed at Stage II in a 77 years-old BRCA1+ woman.

Conclusions: In this sample of healthy northern Italian women carriers of BRCA mutations, close to 10% developed a tumor within 5 years of follow-up with an aggressive cell phenotype. The more accepted method of risk-reduction in this group of women was PO as compared to PM. A protocol of close-surveillance allows for an early stage diagnosis in about half of the women who develop a breast tumor.

Citation Format: Rastelli A, Azzolin F, Tognazzo S, Alducci E, Zovato S. Uptake of risk reducing measures in healthy BRCA 1-2 mutation carriers from Northern Italy: Outcomes of 9 years of close-surveillance. Experience of the hereditary cancer clinic in the region of Veneto, Italy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-07.