Purpose: Li-Fraumeni syndrome (LFS) is a hereditary disorder caused by germline mutation in TP53. Owing to the rarity of LFS, data on its clinical features are limited. This study aimed to evaluate the clinical characteristics and prognosis of Korean patients with LFS. Materials and Methods: Patients who underwent genetic counseling and confirmed with germline TP53 mutation in the National Cancer Center in Korea between 2011 and 2022 were retrospectively reviewed. Data on family history with pedigree, types of mutation, clinical features, and prognosis were collected. Results: Fourteen patients with LFS were included in this study. The median age at diagnosis of the first tumor was 32 years. Missense and nonsense mutations were observed in 13 and one patients, respectively. The repeated mutations were p.Arg273His, p.Ala138Val, and pPro190Leu. The sister with breast cancer harbored the same mutation of p.Ala138Val. Seven patients had multiple primary cancers. Breast cancer was most frequently observed, and other types of tumor included sarcoma, thyroid cancer, pancreatic cancer, brain tumor, adrenocortical carcinoma, ovarian cancer, endometrial cancer, colon cancer, vaginal cancer, skin cancer, and leukemia. The median follow-up period was 51.5 months. Two and four patients showed local recurrence and distant metastasis, respectively. Two patients died of leukemia and pancreatic cancer 3 and 23 months after diagnosis, respectively. Conclusion This study provides information on different characteristics of patients with LFS, including types of mutation, types of cancer, and prognostic outcomes. For more appropriate management of these patients, proper genetic screening and multidisciplinary discussion are required.

Purpose: This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. Materials and Methods: We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. Results: Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022). Conclusion AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.

Purpose: Sentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph nodepositive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC. Methods: This single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND. Results: This study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6–155) in the SLNB group and 99 (range 2–159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001). Conclusion As an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.

Purpose: The ACOSOG Z0011 trial has proven the oncological safety of sentinel lymph node biopsy (SLBx) for node negative breast cancer. Accordingly, treatment paradigm including axilla surgery was changed. We retrospectively reviewed breast cancer patients to evaluate the clinical effect of paradigm shift in breast cancer surgery after applying the Z0011 criteria. Methods: All women who underwent breast-conserving surgery at the National Cancer Center between January 1, 2000, and December 31, 2015, were enrolled and classified according to the Z0011 criteria. The primary endpoint of the study was the disease-free survival rates, and the secondary was the adverse events, especially arm lymphedema. Results: Total 361 patients were enrolled the study (271 axillary lymph node dissection [ALND] group, 90 SLBx group). After the Z0011 guideline was adopted in our institute, the use of ALND decreased, and lymph node sampling (removing only a few axillary lymph nodes) replaced ALND. The total mean number of retrieved nodes were more in ALND group (13.02) than SLBx group (3.43). However, there was no difference in the mean number of positive nodes between two groups (2.34 in ALND group vs. 1.12 in SLBx group, P=0.001). During follow-up, 25 patients experienced disease recurrence: 22 from the ALND group and three from the SLBx group. All of died seven patients were from the ALND group. The ALND group had more complications than the SLBx group (P=0.02). Arm edema occurred more frequently in the ALND group (29.5%) than in the SLBx group (5.6%), although without statistical significance (P=0.07). Conclusion In our study, we concluded that SLBx can be used safely in Z0011-eligible cohort without increased risk of locoregional recurrence. Moreover, we found that omission of ALND is favored to reduce some serious complications such as arm lymphedema.

Background: Aromatase inhibitors (AIs) play an important role in the endocrine therapy of postmenopausal breast cancer patients, with a recent tendency to extend the duration of their use. However, AIs may increase the risk of osteoporotic bone fractures. This meta-analysis evaluated the risk of osteoporotic fractures of the hip, spine, and other locations in breast cancer patients using AIs. Methods: We performed a systematic search to identify randomized controlled clinical trials that investigated osteoporotic fractures in breast cancer patients on AI therapy. The main outcomes were the incidence and risk of osteoporotic fractures in general and of hip, vertebral, and non-vertebral fractures in AI users and controls. Results: The systematic review found a total of 30 randomized controlled trials including 117,974 participants. The meta-analysis showed a higher incidence of osteoporotic fracture in AI users: The crude risk ratio for all osteoporotic fractures was 1.35 (95% confidence interval [CI], 1.29–1.42;P < 0.001), for hip fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), for vertebral fractures 1.84 (95% CI, 1.36–2.49; P < 0.001), and for non-vertebral fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), respectively, compared to the controls. Conclusion Our meta-analysis suggested an increased risk of osteoporotic fractures for AI therapy in patients with breast cancer that was most expressed for vertebral fractures. Breast cancer patients on AIs need to be monitored for osteoporosis and osteoporotic fractures, and active prevention measures should be implemented.

Purpose: This study aimed to determine the incidence of male breast cancer (MBC) and its survival outcomes in Korea, and to compare these results to those for female breast cancer (FBC). Materials and Methods: We searched the Korea Central Cancer Registry and identified 227,122 breast cancer cases that were diagnosed between 1999 and 2016. Demographic and clinical characteristics and overall survival (OS) rates were estimated according to sex, age, histological type, and cancer stage. Results: The 227,122 patients included 1,094 MBC cases and 226,028 FBC cases. Based on the age-standardized rate, the male: female ratio was 0.0055:1. The most common ages at diagnosis were 60-69 years for MBC and 40-49 years for FBC (p < 0.001). Male patients were less likely than female patients to receive adjuvant radiotherapy (7.5% vs. 21.8%, p < 0.001) or adjuvant chemotherapy (40.1% vs. 55.4%, p < 0.001). The 5-year OS rates after diagnosis were 88.8% for all patients, although it was significantly lower for MBC than for FBC (76.2% vs. 88.9%, p < 0.001). In both groups, older age (≥ 60 years) was associated with shorter survival. The 5-year OS rates for the invasive histological types were 75.8% for men and 89.0% for women. The 5-year OS rates in both groups decreased with increasing cancer stage. Conclusion MBC was diagnosed at older ages than FBC, and male patients were less likely to receive radiotherapy and chemotherapy. The survival outcomes were worse for MBC than for FBC, with even poorer outcomes related to older age, the inflammatory histological types, and advanced stage. It is important that clinicians recognize the differences between FBC and MBC when treating these patients.

BACKGROUND: The fracture risk induced by anti-estrogen therapy in patients with breast cancer remains controversial. The aim of this study was to perform a meta-analysis and systematic review to evaluate the risk of osteoporotic fracture in patients with breast cancer. METHODS: A systematic search was performed to identify studies that included any osteoporotic fracture (hip fracture and vertebral fracture) in patients breast cancer. Main outcome measures were occurrence and risk of osteoporotic fractures including hip and vertebral fractures in patients and controls. RESULTS: A systematic search yielded a total of 4 studies that included osteoporotic fracture outcomes in patients with breast cancer. Meta-analysis showed a higher risk of osteoporotic fracture in patients with breast cancer. Analysis of these 4 studies involving a total of 127,722 (23,821 cases and 103,901 controls) patients showed that the incidence of osteoporotic fractures was higher in the breast cancer group than in the control group. The pooled estimate of crude relative risk for osteoporotic fracture was 1.35 (95% confidence interval, 1.29–1.42; P<0.001). CONCLUSIONS Although studies were limited by a small number, results suggested a possible association between anti-estrogen therapy and increased risk of osteoporotic fractures in patients with breast cancer.

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.

BACKGROUND: The effects of subclinical hyperthyroidism on fracture risk induced by thyroid-stimulating hormone (TSH) suppression therapy in patients with thyroid cancer still remains controversial. We performed a meta-analysis and systematic review to evaluate the effects of TSH suppression therapy on osteoporotic fracture in patients with thyroid cancer. METHODS: We performed a systematic search to identify studies which included osteoporotic fractures (hip fracture and vertebral fracture) in patients on TSH suppression therapy for thyroid cancer. Main outcome measures were occurrence and risk of osteoporotic fractures including hip and vertebral fractures between patients and controls. RESULTS: A systematic search yielded a total of 8 studies appropriate for review which included osteoporotic fracture outcome in patients on TSH suppression therapy for thyroid cancer. Studies with larger number of subjects showed the higher risk of osteoporotic fracture in group with TSH suppression therapy, although studies with smaller sample size presented a similar risk of fracture with control group. CONCLUSIONS: Although studies were limited by small numbers, results suggested possible association between chronic TSH suppression therapy and the increased risk of osteoporotic fractures in patients with thyroid cancer.
Hip ; Humans ; Hyperthyroidism ; Osteoporotic Fractures ; Outcome Assessment (Health Care) ; Sample Size ; Thyroid Gland ; Thyroid Neoplasms ; Thyrotropin

PURPOSE: The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers. MATERIALS AND METHODS: The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management. RESULTS: Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001). CONCLUSION: RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.
Breast ; Breast Neoplasms ; Female ; Humans ; Korea ; Male ; National Health Programs ; Ovarian Neoplasms ; Prophylactic Surgical Procedures