Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant

Purpose: Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data. Materials and methods: The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer-related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study. Results: The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations. Conclusion: L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.ope

Trends in contralateral prophylactic mastectomy rate according to clinicopathologic and socioeconomic status

PURPOSE: There has been an increasing trend in the use of contralateral prophylactic mastectomy (CPM) among women diagnosed with unilateral breast cancer or mutations in BRCA1 or BRCA2 to reduce the occurrence of contralateral breast cancer. This study aimed to examine trends in the CPM rate according to clinicopathologic and socioeconomic status at a single institution in Korea. METHODS: This study included 128 patients with mutations in BRCA1 or BRCA2. Patients were divided into a CPM group (n = 8) and a non-CPM group (n = 120) between May 2013 and March 2016. The main outcome variables, including epidemiology, clinical features, socioeconomic status, and tumor characteristics, were analyzed. RESULTS: A total of 8 CPMs were performed among 128 patients. All CPM patients were married. The proportion of professional working women was higher in the CPM group (P = 0.049). Most patients who underwent CPM graduated college, compared to less than a third of the non-CPM group (P = 0.013). The CPM group had a higher rate of visits to the Hereditary Breast and Ovarian Cancer (HBOC) clinic (P = 0.021). The risk-reducing salpingo-oophorectomy (RRSO) rate was significantly higher in the CPM group (P < 0.01). CONCLUSION: CPM rates were significantly different according to socioeconomic status. The CPM rate tends to increase in highly educated and professional working women. The socioeconomic status of patients is an important factor in the decision to participate in the HBOC clinic and undergo CPM or RRSO.ope

Trends in Risk-Reducing Mastectomy and Risk-Reducing Salpingo-Oophorectomy in Korean Carriers of the BRCA1/2 Mutation

Purpose: BRCA1/2 mutations are associated with risks of breast and ovarian cancer. In Korea, incidences of BRCA1/2 genetic testing and risk-reducing surgery (RRS) have increased with insurance coverage and the Angelina Jolie effect. The aim of this study was to identify trends in RRS performed in Korean women with the BRCA1/2 mutation. Methods: We retrospectively reviewed the medical records of BRCA1/2 mutation carriers with (affected carriers) and without (unaffected carriers) breast cancer until August 2018 from 25 Korean Hereditary Breast Cancer (KOHBRA)-affiliated hospitals. Results: The numbers of contralateral risk-reducing mastectomy (RRM) and risk-reducing bilateral salpingo-oophorectomy (RRBSO) in affected carriers have increased 5.8- and 3.6-fold, respectively, since 2013. The numbers of RRBSO in unaffected carriers has increased 8-fold since 2013. The number of institutions that perform RRS has increased gradually. The number of hospitals that perform contralateral RRM on affected carriers increased from 3 in 2012 to 11 in 2018, and that of those that perform RRBSO increased from 7 to 17. The number of hospitals that perform bilateral RRM on unaffected carriers increased from 1 in 2012 to 2 in 2018, and that of those that perform RRBSO increased from 1 to 8. However, the hospitals showed differences in the rates of RRM or RRBSO performed. Conclusion: The incidence of RRS increased each year throughout the study period. However, in Korea, the rate of RRS procedures depended on the hospital.ope

Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

BACKGROUND: Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. METHODS: In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR), and human epithelial receptor-2 (HER2) were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC) according to ER, PR, and HER2 status. RESULTS: Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. CONCLUSIONS: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.ope

Clinicopathological features and prognosis associated with breast cancer laterality: a nationwide study from the Korean Breast Cancer Society

Purpose: Although breast cancer is known to show a left predominance, the clinical characteristics and causes underlying this finding remain unclear. In addition, no related studies on breast cancer laterality have been conducted in patients with breast cancer in Korea. Therefore, we aimed to analyze differences in breast cancer laterality and the associated clinicopathological characteristics and prognosis among Korean patients with breast cancer. Methods: We conducted a retrospective analysis using large-scale data on clinicopathological factors and prognosis differences related to breast cancer laterality from the Korean Breast Cancer Society Registration system. The left-to-right ratio (LRR) of breast cancer was calculated through binomial distribution, and factors related to breast cancer laterality were identified through logistic regression analysis. In addition, the differences in the survival rates for left and right breast cancers were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Results: In 171,500 patients, the LRR was 1.031 (95% confidence interval, 1.022-1.041; P < 0.001). Multivariate analysis showed that the ratio of left breast cancer was related to age, body mass index (BMI), location, and human epidermal growth factor receptor 2 (HER2) status. The survival rate of patients with left and right breast cancers showed no significant difference. Conclusion: A large-scale analysis revealed a left predominance in breast cancer laterality in Korean patients. Over time, this predominance gradually decreased. Age, BMI, location, and HER2 status affected breast cancer laterality. However, while left breast cancer showed relatively aggressive characteristics, it was not associated with a difference in the survival rate.ope

Comparisons of Oncologic Outcomes between Triple-Negative Breast Cancer (TNBC) and Non-TNBC among Patients Treated with Breast-Conserving Therapy

PURPOSE: The optimum local surgical strategy regarding breast-conserving therapy (BCT) for triple-negative breast cancer (TNBC) is controversial. To investigate whether BCT is appropriate for patients with TNBC, we evaluated the clinical outcomes of BCT in women with TNBC compared to those of women without TNBC, using a large, single-center cohort. MATERIALS AND METHODS: We performed a retrospective analysis of 1533 women (TNBC n=321; non-TNBC n=1212) who underwent BCT for primary breast cancer between 2000 and 2010. Clinicopathological characteristics, locoregional recurrence-free survival (LRFS), and overall survival (OS) were analyzed. RESULTS: Tumors from the TNBC group had a higher T stage (T2 37.4% vs. 21.0%, p<0.001), a lower N stage (N0 86.9% vs. 75.5%, p<0.001), and a higher histologic grade (Grade III 66.8% vs. 15.4%, p<0.001) than the non-TNBC group. There were no differences in 5-year LRFS rates between the TNBC and non-TNBC groups (98.7% vs. 97.8%, p=0.63). The non-TNBC group showed a slightly better 5-year OS than the TNBC group; however, the difference was not significant (96.2% vs. 97.3%, p=0.72). In multivariate analyses, TNBC was not associated with poor clinical outcomes in terms of LRFS and OS [hazard ratio (HR) for LRFS=0.37, 95% confidence interval (CI): 0.10-1.31; HR for OS=1.03, 95% CI: 0.31-3.39]. CONCLUSION: TNBC patients who underwent BCT showed non-inferior locoregional recurrence compared to non-TNBC patients with BCT. Thus, BCT is an acceptable surgical approach in patients with TNBC.ope

A Prospective Randomized Study to Compare Postoperative Drainage After Mastectomy Using Electrosurgical Bipolar Systems and Conventional Electro-Cautery

Purpose: Advanced energy devices, including electrosurgical bipolar systems or ultrasonic shears, are widely used in various surgeries. An electrosurgical bipolar device allows surgeons to grasp and dissect tissues, as well as simultaneously ligate and cut vessels and lymphatics during surgery. This study aimed to evaluate the effects of advanced bipolar energy devices on the reduction in seroma formation during mastectomy, axillary staging, and/or reconstruction. Methods: This prospective randomized clinical trial with a 1:1 ratio compared the use of an electrosurgical bipolar device, LigaSureTM (LGS), against conventional cut-and-ligate techniques in mastectomy with axillary procedures for patients with breast cancer. A total of 82 patients with breast cancer who underwent definitive surgery were enrolled in this study. The primary endpoint was the total drainage volume after surgery. Results: The clinicopathological characteristics of the two groups were not significantly different. The total postoperative drainage volume was significantly lower in the LGS group than in the control group (756.26 mL vs. 1,167.74 mL, p = 0.009). The actual postoperative drainage volume and duration also decreased significantly in the LGS group compared with those in the control group (all p < 0.05). The rate of postoperative complications was lower in the LGS group than in the control group (9.8% vs. 27.5%, p = 0.05). Conclusion: Electrosurgical bipolar devices showed better performance in terms of decreasing postoperative drainage during mastectomy and axillary staging and/or reconstruction.ope

A Randomized Controlled Trial for Doing vs. Omitting Intraoperative Frozen Section Biopsy for Resection Margin Status in Selected Patients Undergoing Breast-Conserving Surgery (OFF-MAP Trial)

Purpose: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods: This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the "frozen section biopsy" or "frozen section biopsy omission" group after lumpectomy. Patients with clinical stage T1-T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness. Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy. We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety. Trial registration: ClinicalTrials.gov Identifier: NCT03975179; Clinical Research Information Service Identifier: KCT0004606.ope

Single-port robot-assisted prosthetic breast reconstruction with the da Vinci SP Surgical System: first clinical report

Robot-assisted nipple-sparing mastectomy with immediate reconstruction is currently performed in an attempt to seek smaller and indistinct incisions. Robotic surgery system has been evolving under the concept of minimal invasive technique which is a recent trend in surgery. One of the latest version is the da Vinci SP Surgical System (Intuitive Surgical). In this report, we will share our experiences. Two patients underwent robot-assisted nipple-sparing mastectomy, each followed by immediate robot-assisted expander insertion and prepectoral direct-to-implant breast reconstruction, respectively. There was no open conversion or major postoperative complication. One patient experienced mild infection, which was resolved by intravenous antibiotic treatment. Simple docking process, multi-joint instruments, and third-arm functionality are among the new surgical system's advantages. The present cases suggest that robot-assisted nipple-sparing mastectomy with immediate reconstruction using the da Vinci SP Surgical System is feasible and safe. The promising features and potential application of da Vinci SP in breast reconstruction need further study.ope

Adjuvant Hormonal Therapy: Current Standard and Practical Issues

Adjuvant hormonal therapy is used as the first target-specific approach in curing breast cancers due to its high efficacy and mild side effects. Five years of tamoxifen therapy has been the gold standard for women with estrogen receptor-positive breast cancer irrespective of age or menopausal and nodal status. After the emergence of 3rd generation aromatase inhibitors (AI), the use of either tamoxifen or tamoxifen plus ovarian function suppression for 5 years has been proposed as an acceptable standard for premenopausal women while AI should form part of standard endocrine therapy for the postmenopausal women as established at the St. Gallen Concensus Conference. The addition of luteinizing-hormone-releasing hormone (LHRH) analogs might be beneficial for the younger patients who remain premenopausal after chemotherapy, however controversies over the addition of LHRH analogs remains. Further, it has been suggested that CYP2D6 polymorphisms and concomitant use of CYP2D6 inhibitors which reduce CYP2D6 activity may influence the clinical outcomes of adjuvant tamoxifen therapy. The androgen receptor has been evaluated as a prognostic or predictive marker for endocrine responsiveness in a few studies; however, there are many issues to be answered and ongoing clinical trials will provide the answers. Until then, it would be important for clinicians to carefully evaluate the risk factors of patients, monitor the compliance of those patients who are under endocrine therapy, and take care in selecting antidepressants when coprescription with tamoxifen is necessary. In the future, tailored therapy will be designed based on the target molecular profiling of the tumors, pharmacogenomics, and improved understanding of receptor signaling biology. More attention should be given to explore molecular markers that could differentiate the subsets for tailoringope