L.B. Koppert

Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis

BACKGROUND To prospectively assess the efficacy of bilateral risk-reducing mastectomy (BRRM) when compared with surveillance on breast cancer (BC) risk and mortality in healthy BRCA1 and BRCA2 mutation carriers. PATIENTS AND METHODS Five hundred and seventy healthy female mutation carriers (405 BRCA1, 165 BRCA2) were selected from the institutional Family Cancer Clinic database. Eventually, 156 BRCA1 and 56 BRCA2 mutation carriers underwent BRRM. The effect of BRRM versus surveillance was estimated using Cox models. RESULTS During 2037 person-years of observation (PYO), 57 BC cases occurred in the surveillance group versus zero cases during 1379 PYO in the BRRM group (incidence rates, 28 and 0 per 1000 PYO, respectively). In the surveillance group, four women died of BC, while one woman in the BRRM group presented with metastatic BC 3.5 years after BRRM (no primary BC), and died afterward, yielding a HR of 0.29 (95% CI 0.02-2.61) for BC-specific mortality. CONCLUSIONS In healthy BRCA1/2 mutation carriers, BRRM when compared with surveillance reduces BC risk substantially, while longer follow-up is warranted to confirm survival benefits.

Breast and Tumour Volume Measurements in Breast Cancer Patients Using 3-D Automated Breast Volume Scanner Images

BackgroundThe resection volume in relation to the breast volume is known to influence cosmetic outcome following breast-conserving therapy. It was hypothesised that three-dimensional ultrasonography (3-D US) could be used to preoperatively assess breast and tumour volume and show high association with histopathological measurements.MethodsBreast volume by the 3D-US was compared to the water displacement method (WDM), mastectomy specimen weight, 3-D MRI and three different calculations for breast volume on mammography. Tumour volume by the 3-D US was compared to the histopathological tumour volume and 3-D MRI. Relatedness was based on the intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95% CI). Bland–Altman plots were used to graphically display the agreement for the different assessment techniques. All measurements were performed by one observer.ResultsA total of 36 patients were included, 20 and 23 for the evaluation of breast and tumour volume (ductal invasive carcinomas), respectively. 3-D US breast volume showed ‘excellent’ association with WDM, ICC 0.92 [95% CI (0.80–0.97)]. 3-D US tumour volume showed a ‘excellent’ association with histopathological tumour volume, ICC 0.78 [95% CI (0.55–0.91)]. Bland–Altman plots showed an increased overestimation in lager tumour volumes measured by 3-D MRI compared to histopathological volume.Conclusions3-D US showed a high association with gold standard WDM for the preoperative assessment of breast volume and the histopathological measurement of tumour volume. 3-D US is an patient-friendly preoperative available technique to calculate both breast volume and tumour volume. Volume measurements are promising in outcome prediction of intended breast-conserving treatment.

Gamma probe and ultrasound-guided fine needle aspiration cytology of the sentinel node (GULF) trial

PurposeSentinel lymph node biopsy (SLNB) was introduced as a minimally invasive technique for nodal staging. Since associated morbidity is not negligible, it is highly relevant to pursue a more minimally invasive alternative. The purpose of this study was to prospectively evaluate the sensitivity of fine needle aspiration cytology (FNAC) with combined gamma probe and ultrasound (US) guidance in comparison with the gold standard histology of the sentinel node (SN) after SLNB for detecting metastasis.MethodsThe study was designed as a prospective, multicentre, open-label, single-arm trial enrolling patients with newly diagnosed cutaneous melanoma or breast cancer between May 2015 and August 2017. Sample radioactivity was measured using a Mini 900 scintillation monitor. After FNAC, all patients underwent SLNB. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were estimated.ResultsAccrual was terminated early following an unplanned interim analysis indicating that a FNAC sensitivity of at least 80% could not be achieved. In total 58 patients of the originally planned 116 patients underwent FNAC with gamma probe and US guidance. There were no true-positive FNAC results, 14 false-negative results and one false-positive result, and thus the sensitivity, specificity, PPV and NPV of FNAC were 0%, 98%, 0% and 75%, respectively. At least 75% of the FNAC samples had a radioactivity signal higher than the background signal.ConclusionFNAC with gamma probe and US guidance is not able to correctly detect metastases in the SN and is therefore not able to replace SLNB. Gamma probe-guided US is a highly accurate method for correctly identifying the SN, which offers possibilities for future research.

Abstract P5-05-05: Lower mitotic activity in BRCA1/2-associated primary breast cancers occurring after risk-reducing salpingo-oophorectomy

Background Bilateral salpingo-oophorectomy reduces breast cancer (BC) risk by about 50% in BRCA1/2 mutation carriers when performed premenopausally. It has been hypothesized that growth activity of BCs originating after risk-reducing salpingo-oophorectomy (RRSO) is lower. We compared tumor characteristics and growth rates of BRCA1/2-associated primary BCs (PBCs) detected after RRSO with those of tumors originating without RRSO. Methods From a cohort of 271 female BRCA1/2-associated patients with screen detected BC, 20 BRCA1/2 mutation carriers with PBC detected ≥12 months after RRSO were selected (RRSO group). Controls were 36 BRCA1/2 mutation carriers with PBC detected without RRSO (non-RRSO group) matched for age at PBC diagnosis (± 2.5 years) and for BRCA1 or BRCA2 mutation (intended matching ratio 1:2). Tumor growth rates, expressed as tumor volume doubling times (DT), were calculated. Pathology samples were revised for histological subtype, tumor differentiation grade, estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Imaging examinations (magnetic resonance imaging (MRI), mammography) before and at BC diagnosis were revised. Results Median age at PBC diagnosis was 52 years (range 35-67). MRI detected more BC than mammography in the RRSO-group as compared to the non-RRSO group (83% vs. 39%, P = 0.02). Tumor size at diagnosis was smaller in the RRSO group (11.0 mm vs. 17.0 mm, P = 0.01). Mitotic activity indexes (MAI) in the RRSO and non-RRSO group were 12 vs. 22 mitotic counts/2 mm 2 (P = 0.02). No significant differences in differentiation grade, ER and HER2 status were found. PR-status was more often positive in the RRSO group without reaching statistical significance (38% vs. 13%, P = 0.07). Median DT in the RRSO group was 124 days (range 89-193) and 93 days (range 54-253) in the non-RRSO group (P = 0.47). Conclusion BC occurring after RRSO in BRCA mutation carriers features a lower MAI, suggesting a less aggressive biological behavior. When confirmed in larger series, this may have consequences for BC screening protocols for BRCA1/2 mutation carriers after RRSO. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-05-05.