Prevalence and Impact of Variants of Uncertain Significance on Local Therapy Decision-Making in Newly Diagnosed Breast Cancer Patients

Abstract

IORT; PB-IORT) or deep inspiratory breath hold external beam radiation therapy (EBRT-DIBH) for early stage left sided breast cancers at our institution. Materials/Methods: We retrospectively identified the 17 patients with left sided breast cancers treated with PB-IORT on a phase I clinical trial. 17 patients with left-sided tumors who had undergone lumpectomy and adjuvant EBRT-DIBH during a similar time period were identified for comparison. Dosimetric data was obtained for mean and maximum heart and left anterior descending artery (LAD) doses. T-testing analysis was performed, and biologically effective doses (BED) were calculated using an alpha/beta ratio for heart of 2 Gy. Results: Mean heart dose was found to be significantly lower in the EBRT-DIBH group compared to the IORT group (0.61 vs. 0.87 Gy, pZ0.006). Nominal maximum heart dose was significantly higher in the EBRT-DIBH group (11.37 vs. 4.81 Gy, pZ0.004). BED for maximum heart dose was similar between the EBRT-DIBH and IORT groups, 16.63 vs. 19.36 Gy, respectively (pZ0.64). No difference was found in mean left anterior descending (LAD) artery dose: 2.18 Gy in the EBRT-DIBH group and 1.89 Gy in the IORT group (pZ0.446). The maximum LAD doses were 9.63 Gy and 3.62 Gy in the EBRT-DIBH and IORT groups, respectively (pZ0.016). Conclusion: Heart doses were found to be low in both groups. Expected increase in cardiac risk at these doses is minimal. It is unlikely that there will be a clinically significant difference in cardiac toxicity in patients treated with EBRT-DIBH or PB-IORT.

Clinical management among individuals with variant of uncertain significance in hereditary cancer: A systematic review and meta‐analysis

“…Table 1 provides the characteristics of the included studies. Of the included 22 papers,17 reported surgical outcomes, 10,15‐17,19‐21,23‐25,27‐30,32,34,35 including mastectomy, lumpectomy, and oophorectomy, and six reported cancer screening outcomes, 16,17,20,21,27,32 including mammography, breast MRI, TVUS, CA‐125 testing, and colonoscopy. Studies were published between 2011 and 2020 representing data collected between 1995 and 2019.…”

“…Five studies 16,23,28,30,34 reported therapeutic mastectomy rates among breast cancer patients with VUS vs P/LP (Figure 3) and VUS vs B/LB genetic test results (Figure 4). Pooled data from three studies 16,23,28 showed no difference in mastectomy rates between patients with VUS vs P/LP results or among patients with VUS vs B/LB results.…”

“…Therapeutic breast conservation or lumpectomy was reported in 5 16,23,28,30,34 studies. Overall, breast conservation or lumpectomy rates were not significantly different between patients with VUS and P/LP results (OR = 0.47, 95% CI, 0.12–1.83; I 2 = 83%) or between patients with VUS and B/LB (OR = 0.84, 95% CI, 0.59–1.20; I 2 = 0%).…”