The yield and effectiveness of breast cancer surveillance in women with PTEN Hamartoma Tumor Syndrome

Abstract

BACKGROUND:Women with PTEN Hamartoma Tumor Syndrome (PHTS) are offered breast cancer (BC) surveillance because of an increased BC lifetime risk. Surveillance guidelines are, however, expert opinion-based because of a lack of data. We aimed to assess the yield and effectiveness of BC surveillance and the prevalence and type of breast disease in women with PHTS. METHODS: Sixty-five women with PHTS who visited our center between 2001 and 2021 were included. Surveillance consisted of annual magnetic resonance imaging (MRI) and mammography from ages 25 and 30 years, respectively. RESULTS: Thirty-nine women enrolled in the BC surveillance program (median age at first examination, 38 years [range, 24-70]) and underwent 156 surveillance rounds. Surveillance led to detection of BC in 7/39 women (cancer detection rate [CDR], 45/1000 rounds) and benign breast lesions (BBLs) in 11/39 women. Overall sensitivity 2 (which excludes prophylactic-mastectomy detected BCs) was 100%, whereas sensitivity 2 of mammography and MRI alone was 50% and 100%, respectively. Overall specificity was higher in follow-up rounds (86%) versus first rounds (71%). Regardless of surveillance, 21/65 women developed 35 distinct BCs (median age at first diagnosis, 40 years [range, 24-59]) and 23/65 developed 89 BBLs (median age at first diagnosis, 38 years [range, 15-61]). Surveillance-detected BCs were all T1 and N0, whereas outside surveillance-detected BCs were more often ≥T2 (60%) and N+ (45%) (p < .005). CONCLUSIONS: The findings show that annual BC surveillance with MRI starting at age 25 years enables detection of early-stage BCs. Performance measures of surveillance and CDR were both high. BBLs were commonly present, underlining the importance of evaluation of all lesions independently.

Enhancing breast cancer detection in PTEN Hamartoma Tumor Syndrome through insights into MRI and mammography lesion features

“…Both the sensitivity (100%) and speci city (82%) of the combined modalities were found to be high. However, consistent with ndings from studies in high-risk populations (MRI: 71-96%, mammography: 19-51%) [11][12][13], MRI demonstrated superior sensitivity (100%) compared to mammography (50%) when these modalities were assessed independently [10]. Similarly, despite the individual speci city of mammography (92%) and MRI (84%) being both adequate, MRI alone was responsible for the diagnosis of BC in 3 out of 5 women who underwent both imaging modalities.…”

“…However, the speci c appearance of BCs in women with PHTS remains under-explored. Considering the relatively high prevalence of benign breast lesions (BBLs) (46%) in this group [10], studies describing both benign and malignant imaging characteristics could further increase sensitivity and speci city of the surveillance program. Additionally, such data could inform expert opinion-based guidelines and potentially lead to a reevaluation of mammography use, speci cally in young women with PHTS.…”

“…Recent studies have demonstrated the effectiveness of BC surveillance in women with PHTS. Notably, the cancer detection rate (CDR) achieved through annual surveillance is impressive (45 per 1000 rounds [95% CI, 20-94]) [10]. Both the sensitivity (100%) and speci city (82%) of the combined modalities were found to be high.…”

Challenges and Changes of the Breast Cancer Screening Paradigm

“…Recently, Hoxhaj et al reported a CDR with MRI of 45 per 1000 rounds (95% CI, 20–94) in PTEN mutation carriers. This is comparable to (or even higher than) the CDR of MRI in BRCA1/2 mutation carriers suggesting that the two high risk groups are indeed comparable and the imaging surveillance should be the same 54 . The role of screening with MRI for women with pathogenic variants of ATM, CHEK2, and PALB2 mutation carriers is currently investigated, suggesting a similar beneficial effect 55 …”

“…This is comparable to (or even higher than) the CDR of MRI in BRCA1/2 mutation carriers suggesting that the two high risk groups are indeed comparable and the imaging surveillance should be the same. 54 The role of firstand second-degree family history, including unaffected relatives, and allows for multiple genes with variable penetrance. 28,59,60 Also women with a personal history of breast cancer have an elevated risk of breast cancer recurrence with a cumulative incidence of 5.4% in 5 years.…”