Selective Avoidance of Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy in Human Epidermal Growth Factor 2-Positive/TripleNegative Breast Cancer Patients With Excellent Response / 한국유방암학회지

Purpose@#The Avoid Axillary Sentinel Lymph Node Biopsy After Neoadjuvant Chemotherapy (ASLAN) trial aims to demonstrate the oncologic safety of omitting axillary surgery in patients with excellent response after neoadjuvant chemotherapy (NACT) for early human epidermal growth factor 2 (HER2)-positive (+)/triple-negative breast cancer (TNBC) who have undergone breast-conserving surgery (BCS) and adjuvant radiotherapy. The ASLAN trial will provide crucial information that could change the procedure in highly selected patients undergoing axillary surgery after NACT. @*Methods@#ASLAN is a prospective, multicenter, and single-arm surgical trial. The recruitment will be conducted among five tertiary care hospitals in the Republic of Korea. The total number of patients to be recruited will be 178, and we plan to complete patient enrollment by December 2023. The enrollment is considered among patients with HER2+ breast cancer (BC) or TNBC at clinical stage T1–3N0–1M0 who are expected to achieve breast pathological complete response (BpCR) based on a combination of radiologic imaging and physical examination after NACT. BCS was performed on eligible patients. After BCS, patients who showed BpCR were enrolled with the omission of sentinel lymph node biopsy (SLNB). The primary study endpoint upon completion of this trial is 5-year recurrence-free survival, and the secondary endpoints include the 5-year ipsilateral breast tumor recurrence interval, 5-year ipsilateral axillary recurrence interval, 5-year distant metastasis-free survival, 5-year BC-specific survival, 5-year overall survival, 5-year contralateral BC-free survival, re-operation rate according to breast biopsy after NACT, adverse events within 5 years, and quality of life.Discussion: Several clinical trials are currently underway to determine whether SLNB can be omitted after NACT in patients with HER2+ BC or TNBC that are expected to achieve pathologic complete response. The ASLAN trial is expected to provide valuable clues regarding the feasibility of omitting axillary surgery in highly selected patients.

Omission of Breast Surgery in Predicted Pathologic Complete Response after Neoadjuvant Systemic Therapy: A Multicenter, Single-Arm, Non-inferiority Trial / 한국유방암학회지

Purpose@#Advances in chemotherapeutic and targeted agents have increased pathologic complete response (pCR) rates after neoadjuvant systemic therapy (NST). Vacuum-assisted biopsy (VAB) has been suggested to accurately evaluate pCR. This study aims to confirm the non-inferiority of the 5-year disease-free survival of patients who omitted breast surgery when predicted to have a pCR based on breast magnetic resonance imaging (MRI) and VAB after NST, compared with patients with a pCR who had undergone breast surgery in previous studies. @*Methods@#The Omission of breast surgery for PredicTed pCR patients wIth MRI and vacuumassisted bIopsy in breaST cancer after neoadjuvant systemic therapy (OPTIMIST) trial is a prospective, multicenter, single-arm, non-inferiority study enrolling in 17 tertiary care hospitals in the Republic of Korea. Eligible patients must have a clip marker placed in the tumor and meet the MRI criteria suggesting complete clinical response (post-NST MRI size ≤ 1 cm and lesion-to-background signal enhancement ratio ≤ 1.6) after NST. Patients will undergo VAB, and breast surgery will be omitted for those with no residual tumor. Axillary surgery can also be omitted if the patient was clinically node-negative before and after NST and met the stringent criteria of MRI size ≤ 0.5 cm. Survival and efficacy outcomes are evaluated over five years.Discussion: This study seeks to establish evidence for the safe omission of breast surgery in exceptional responders to NST while minimizing patient burden. The trial will address concerns about potential undertreatment due to false-negative results and recurrence as well as improved patient-reported quality of life issues from the omission of surgery. Successful completion of this trial may reshape clinical practice for certain breast cancer subtypes and lead to a safe and less invasive approach for selected patients.

Role of Doppler US and elastography prior to biopsy to identify candidates for avoidance of surgery following neoadjuvant chemotherapy for breast cancer

Purpose@#This study aimed to evaluate the role of Doppler ultrasound (US) and elastography to identify residual breast cancer for patients showing near complete response following chemotherapy on magnetic resonance imaging (MRI). @*Methods@#Between September 2016 and January 2018, 40 breast cancer patients who showed near complete response (either tumor size ≤0.5 cm or lesion-to-background parenchymal signal enhancement ratio ≤1.6) on MRI following neoadjuvant chemotherapy were prospectively enrolled. After excluding seven women who did not undergo Doppler US and elastography, 33 women (median age, 49 years; range, 32 to 67 years) were analyzed. On the day of surgery, women underwent Doppler US and elastography for tumor bed prior to US-guided core needle biopsy. Histopathologic results of biopsy and surgery were evaluated. Negative predictive value (NPV) and false negative rate (FNR) of biopsy and the combined Doppler US and elastography were analyzed, respectively. @*Results@#After surgery, nine women had residual cancers and 24 women had pathologic complete response. The NPV and FNR of biopsy were 92% (24 of 26) and 22% (2 of 9), respectively. The NPV and FNR of combined Doppler US and elastography were 100% (14 of 14) and 0% (0 of 9), respectively. All of nine women with residual cancers had positive vascularity or elasticity. Two women with false-negative biopsy results, having 0.3 cm or 2.5 cm ductal carcinoma in situ at surgery, showed positive vascularity or elasticity. @*Conclusion@#Tumor bed showing positive vascularity or elasticity indicates residual breast cancer for patients showing near complete response on MRI following chemotherapy.

Retrospective Cohort Study on the Long-term Oncologic Outcomes of Sentinel Lymph Node Mapping Methods (Dye-Only versus Dye and Radioisotope Mapping) in Early Breast Cancer: A Propensity Score-Matched Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#In sentinel lymph node (SLN) biopsy (SLNB) during breast cancer surgery, SLN mapping using dye and isotope (DUAL) may have lower false-negative rates than the dye-only (DYE) method. However, the long-term outcomes of either method are unclear. We aimed to compare long-term oncological outcomes of DYE and DUAL for SLNB in early breast cancer. @*Materials and Methods@#This retrospective single-institution cohort study included 5,795 patients (DYE, 2,323; DUAL, 3,472) with clinically node-negative breast cancer who underwent SLNB and no neoadjuvant therapy. Indigo carmine was used for the dye method and Tc99m-antimony trisulfate for the isotope. To compare long-term outcomes, pathologic N0 patients were selected from both groups, and propensity score matching (PSM), considering age, pT category, breast surgery, and adjuvant treatment, was performed (1,441 patients in each group). @*Results@#The median follow-up duration was 8.7 years. The median number of harvested sentinel nodes was 3.21 and 3.12 in the DYE and DUAL groups, respectively (p=0.112). The lymph node–positive rate was not significantly different between the two groups in subgroups of similar tumor sizes (p > 0.05). Multivariate logistic regression revealed that the mapping method was not significantly associated with the lymph node–positive rate (p=0.758). After PSM, the 5-year axillary recurrence rate (DYE 0.8% vs. DUAL 0.6%, p=0.096), and 5-year disease-free survival (DYE 93.9% vs. DUAL 93.7%, p=0.402) were similar between the two groups. @*Conclusion@#Dye alone for SLNB was not inferior to dual mapping regarding long-term oncological outcomes in early breast cancer.

Residual Risk of Ipsilateral Tumor Recurrence in Patients Who Achieved Clear Lumpectomy Margins After Repeated Resection / 한국유방암학회지

Purpose@#Patients with breast cancer with positive lumpectomy margins have a two-fold increased risk of ipsilateral breast tumor recurrence (IBTR). This can be the result of either technically incomplete resection or the biological characteristics of the tumor that lead to a positive margin. We hypothesized that if achieving negative margins by re-excision nullifies the IBTR risk, then the increased risk is mainly attributed to the technical incompleteness of the initial surgeries. Thus, we investigated IBTR rates in patients with breast cancer who achieved clear margins after re-excision. @*Methods@#We retrospectively reviewed patients who underwent breast lumpectomy for invasive breast cancer between 2004 and 2018 at a single institution, and investigated IBTR events. @*Results@#Among 5,598 patients, 793 achieved clear margins after re-excision of their initial positive margins. During the median follow-up period of 76.4 months, 121 (2.2%) patients experienced IBTR. Patients who underwent re-excision to achieve negative margin experienced significantly higher IBTR rates compared to those achieving clear margin at first lumpectomy (10-year IBTR rate: 5.3% vs. 2.6% [25 vs. 84 events]; unadjusted p = 0.031, hazard ratio, 1.61, 95% confidence interval [CI], 1.04–2.48; adjusted p = 0.030, hazard ratio, 1.69, 95% CI, 1.05–2.72). This difference was more evident in patients aged < 50 years and those with delayed IBTR. Additionally, no statistically significant differences were observed in the spatial distribution of IBTR locations. @*Conclusion@#Patients who underwent re-excision for initial positive margins had an increased risk of IBTR, even after achieving a final negative margin, compared to patients with negative margins initially. This increased risk of IBTR is mostly observed in young patients and delayed cases.

Comparison of Quality of Life and Cosmetic Outcome of Latissimus Dorsi Mini-Flap With Breast Conservation Surgery Without Reconstruction / 한국유방암학회지

Purpose@#Latissimus dorsi mini-flap (LDMF) reconstruction after breast-conserving surgery (BCS) is a useful volume replacement technique when a large tumor is located in the upper or outer portion of the breast. However, few studies have reported the impact of LDMF on patients’ quality of life (QoL) and cosmesis compared with conventional BCS. @*Methods@#We identified patients who underwent BCS with or without LDMF between 2010 and 2020 at a single center. At least 1 year after surgery, we prospectively administered the BREAST-Q to assess QoL and obtained the patients’ breast photographs. The cosmetic outcome was assessed using four panels composed of physicians and the BCCT.core software. @*Results@#A total of 120 patients were enrolled, of whom 62 and 58 underwent LDMF or BCS only, respectively. The LDMF group had significantly larger tumors, shorter nipple-to-tumor distances in preoperative examinations, and larger resected breast volumes than did the BCSonly group (p < 0.001). The questionnaires revealed that QoL was poorer in the LDMF group, particularly in terms of the physical well-being score (40.9 vs. 20.1, p < 0.001). Notably, the level of patients’ cosmetic satisfaction with their breasts was comparable, and the cosmetic evaluation was assessed by panels and the BCCT.core software showed no differences between the groups. @*Conclusion@#Our results showed that cosmetic outcomes of performing LDMF are comparable to those of BCS alone while having the advantage of resecting larger volumes of breast tissue. Therefore, for those who strongly wish to preserve the cosmesis of their breasts, LDMF can be considered a favorable surgical option after the patient is oriented toward the potential for physical dysfunction after surgery.

Life-Threatening Hematoma in an Elderly Breast Cancer Patient Undergoing Chemotherapy / 한국유방암학회지

The use of neoadjuvant chemotherapy in older patients is increasing. However, chemotherapy should be administered considering the medical comorbidities of the patients and the toxicity of chemotherapeutic agents. Here, we present a case of abdominal wall hematoma with spontaneous inferior epigastric artery injury caused by coughing in a 70-year-old woman who was treated with neoadjuvant chemotherapy. Abdominal computed tomography demonstrated an abdominal wall hematoma with active bleeding. However, angiography with selective embolization of the right inferior epigastric artery and the right internal mammary artery was performed successfully. Scheduled chemotherapy was discontinued over concerns of rebleeding and breast-conserving surgery was performed. When deciding on chemotherapy for older patients, attention should be paid to the various complications.

The Usefulness of Ultrasound Surveillance for Axillary Recurrence in Women With Personal History of Breast Cancer / 한국유방암학회지

Purpose@#To evaluate the axillary recurrence rate and usefulness of axillary ultrasound (AUS) during supplementary whole-breast ultrasound (US) screening in women with a personal history of breast cancer (PHBC). @*Methods@#A retrospective database search identified consecutive asymptomatic women who underwent postoperative supplemental whole-breast US screening, including that of the bilateral axillae, after negative findings on mammography between January and June 2017. Using the pathologic data or at least 1-year follow-up data as reference standards, the axillary recurrence rate, cancer detection rate (CDR), interval axillary recurrence rate per 1,000 screenings, sensitivity, specificity, and abnormal interpretation rate (AIR) were estimated. @*Results@#From the data of 4,430 women (mean age, 55.0 ± 10.1 years) analyzed in this study, there were five axillary recurrence cases (1.1/1,000) in the median follow-up period of 57.2 months. AUS showed a CDR of 0.2 (1/4,430; 95% confidence interval [CI], 0.01–1.3) and an interval axillary recurrence rate of 0.9 (4/4,402; 95% CI, 0.2–2.3) per 1,000 examinations. The sensitivity and specificity were 20.0% (1/5; 95% CI, 0.5–71.6), and 99.4% (4,398/4,425; 95% CI, 99.1–99.6), respectively, while the AIR was 0.6% (28/4,430; 95% CI, 0.4–0.9%). @*Conclusion@#In asymptomatic women with a PHBC and negative findings on mammography, axillary recurrence after breast cancer and axillary treatment was uncommon, and the supplemental AUS screening yielded 0.2 cancers per 1,000 examinations.

Surgical Options for Ipsilateral Breast Tumor Recurrence: Mastectomy Versus Repeat Breast-Conserving Surgery

Purpose@#The standard care for patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) is a total mastectomy (TM); however, there is growing interest in repeating BCS for IBTR. @*Methods@#We retrospectively analyzed patients with IBTR who underwent initial BCS for breast cancer at our institution between January 2000 and December 2018. The Kaplan-Meier method was used to compare survival rates between the standard BCS-TM treatment group and the repeat-BCS group. @*Results@#We enrolled 209 IBTR patients with a median follow-up of 102.3 months. No significant differences were observed in overall survival (10 years: 87.3% vs. 78.8%; hazard ratio [HR], 1.11; 95% confidence interval [CI], 0.44-2.81; p=0.821), distant metastasis free survival (10 years: 73.9% vs. 77.7%; HR, 0.80; 95% CI, 0.37-1.72; p=0.727) and disease-free survival (10 years: 57.1% vs. 65.2%; HR, 0.63; 95% CI, 0.35-1.12; p=0.115) between two groups. Repeat-BCS group showed significantly poorer locoregional recurrence free survival rate than did the TM group (HR, 2.44; 95% CI, 1.06-5.56; p=0.029) but the significance was not shown after excluding ipsilateral breast tumor recurrence events. @*Conclusion@#No significant differences were observed in survival outcomes and recurrence rates between patients with IBTR who underwent mastectomy or repeat BCS regardless of molecular subtype, except secondary IBTR rates.

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer. @*Materials and Methods@#We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer. @*Results@#Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05). @*Conclusion@#Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

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) / 한국유방암학회지

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.

Comparison of Long-Term Oncological Outcomes in Oncoplastic Breast Surgery and Conventional BreastConserving Surgery for Breast Cancer: A Propensity Score-Matched Analysis / 한국유방암학회지

Purpose@#The oncoplastic breast-conserving surgery (OPS) technique, combined with the principles of oncological safety and plastic surgery, results in complete tumor resection while preserving the natural appearance of the breast. The purpose of this study was to evaluate the long-term oncological results after OPS compared with conventional breast-conserving surgery (BCS) for early breast cancer. @*Methods@#The medical records of patients who underwent breast cancer surgery and adjuvant radiation therapy at Seoul National University Hospital between 2011 and 2014 were reviewed. Ipsilateral breast tumor recurrence (IBTR)-free survival rate and recurrence-free survival (RFS) rates were compared between the OPS and BCS groups. @*Results@#One-to-one propensity score matching was conducted, yielding 371 patients in each group. The mean tumor distance from the nipple was shorter, and the mean retrieved specimen size and pathologic tumor size, including ductal carcinoma in situ, were larger in the OPS group than in the conventional BCS group (p < 0.001). Surgical margin positivity was not significantly different between the two groups (p = 0.777). The surgical technique was not significantly associated with IBTR (OPS versus conventional BCS, 5-year survival rate, 96.9% vs. 98.6%; p = 0.355) and RFS (5-year survival rate, 92.9% vs. 94.5%; p = 0.357) on the log-rank test. Multivariate analysis revealed that OPS versus conventional BCS was not significantly associated with survival outcomes. @*Conclusion@#We observed no significant differences in long-term IBTR and RFS between the OPS and conventional BCS groups in this retrospective analysis. OPS can be an oncologically and surgically safe alternative option for conventional BCS for early breast cancer.

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations / 한국유방암학회지

Purpose@#Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes;however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. @*Methods@#Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. @*Results@#Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8–222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. @*Conclusion@#As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2.A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Association between Number of Retrieved Sentinel Lymph Nodes and Breast Cancer-related Lymphedema / 한국유방암학회지

Purpose@#Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. @*Methods@#Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. @*Results@#Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). @*Conclusion@#The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.

Impact of Trastuzumab on Ipsilateral Breast Tumor Recurrence for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer after BreastConserving Surgery / 한국유방암학회지

Purpose@#Trastuzumab is effective in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, few studies have reported the effect of trastuzumab on ipsilateral breast tumor recurrence (IBTR), whose incidence is higher in the HER2-positive subtype than in other subtypes. @*Methods@#We retrospectively investigated 959 patients who underwent breast-conserving surgery (BCS), chemotherapy, and radiotherapy for HER2-positive breast cancer between 2000 and 2017. IBTR was compared between the patients who received neoadjuvant or adjuvant trastuzumab (Tmab group) for a total duration of 1 year and those who received no trastuzumab (N-Tmab group). @*Results@#Propensity score matching designated 426 and 142 patients in the Tmab and N-Tmab groups, respectively. The median follow-up period for all patients after matching was 73.79 months. The IBTR-free survival rate was significantly higher in the Tmab group than in the N-Tmab group (10-year IBTR-free survival rate, 92.9% vs. 87.3%; p = 0.002). The multivariate analysis showed a significant association between the N-Tmab and Tmab group (hazard ratio, 3.03; 95% confidence interval, 1.07–8.59) and IBTR in addition to close or positive resection margin and hormone receptor (HR) positivity. The subgroup analysis showed that adjuvant treatment with trastuzumab significantly reduced IBTR among the patients with HR-negative or lymph node-negative breast cancer. @*Conclusion@#Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvanteoadjuvant trastuzumab treatment for HER2-positive breast cancer.

Clinical Features of Breast Cancer in South Korean Patients with Germline TP53 Gene Mutations / 한국유방암학회지

Purpose@#Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes;however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. @*Methods@#Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. @*Results@#Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8–222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. @*Conclusion@#As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2.A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Association between Number of Retrieved Sentinel Lymph Nodes and Breast Cancer-related Lymphedema / 한국유방암학회지

Purpose@#Sentinel lymph node biopsy (SLNB) has become a standard axillary staging surgery for early breast cancer, and the proportion of patients requiring axillary lymph node dissection (ALND) is decreasing. We aimed to evaluate the association between the number of sentinel lymph nodes (SLNs) retrieved and the risk of lymphedema of the ipsilateral arm. @*Methods@#Prospectively collected medical records of 910 patients were reviewed.Lymphedema was defined as a difference in circumference > 2 cm compared to the contralateral arm and/or having clinical records of lymphedema treatment in the rehabilitation clinic. @*Results@#Together with an objective and subjective assessment of lymphedema, 36 patients (6.1%) had lymphedema in the SLNB group and 85 patients (27.0%) had lymphedema in the ALND group (p < 0.001). In a multivariate analysis of the whole cohort, risk factors significantly associated risk with the development of lymphedema were body mass index, mastectomy (vs.breast-conserving surgery), ALND, and radiation therapy. In logistic regression models in the SLNB group only, there was no correlation between the number of retrieved SLNs and the incidence of lymphedema. In addition, in the Pearson correlation analysis, no correlation was observed between the number of retrieved SLNs and the difference in circumference between the ipsilateral and contralateral upper extremities (correlation coefficients = 0.067, p = 0.111). @*Conclusion@#The risk of lymphedema in breast cancer surgery and adjuvant treatments is multifactorial. The number of retrieved lymph nodes during sentinel biopsy was not associated with the incidence of lymphedema.

Impact of Trastuzumab on Ipsilateral Breast Tumor Recurrence for Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer after BreastConserving Surgery / 한국유방암학회지

Purpose@#Trastuzumab is effective in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, few studies have reported the effect of trastuzumab on ipsilateral breast tumor recurrence (IBTR), whose incidence is higher in the HER2-positive subtype than in other subtypes. @*Methods@#We retrospectively investigated 959 patients who underwent breast-conserving surgery (BCS), chemotherapy, and radiotherapy for HER2-positive breast cancer between 2000 and 2017. IBTR was compared between the patients who received neoadjuvant or adjuvant trastuzumab (Tmab group) for a total duration of 1 year and those who received no trastuzumab (N-Tmab group). @*Results@#Propensity score matching designated 426 and 142 patients in the Tmab and N-Tmab groups, respectively. The median follow-up period for all patients after matching was 73.79 months. The IBTR-free survival rate was significantly higher in the Tmab group than in the N-Tmab group (10-year IBTR-free survival rate, 92.9% vs. 87.3%; p = 0.002). The multivariate analysis showed a significant association between the N-Tmab and Tmab group (hazard ratio, 3.03; 95% confidence interval, 1.07–8.59) and IBTR in addition to close or positive resection margin and hormone receptor (HR) positivity. The subgroup analysis showed that adjuvant treatment with trastuzumab significantly reduced IBTR among the patients with HR-negative or lymph node-negative breast cancer. @*Conclusion@#Significantly reduced IBTR after BCS was observed in the patients who received 1 year of adjuvanteoadjuvant trastuzumab treatment for HER2-positive breast cancer.

Omission of axillary lymph node dissection in patients who underwent total mastectomy with 1 or 2 metastatic lymph nodes

Purpose@#Sentinel lymph node biopsy (SLNB) is the standard axillary procedure in early breast cancer patients. In a randomized trial, the survival rates were not different when axillary lymph node dissection (ALND) was omitted in patients with 1 or 2 lymph node metastases who underwent breast conserving surgery. This study aimed to compare the outcomes in patients who underwent total mastectomy (TM) with 1 or 2 metastatic nodes according to the types of axillary surgery. @*Methods@#In total, 79,058 patients registered in the Korean Breast Cancer Society database who underwent TM were included in the analysis. The inclusion criteria were history of TM and SLNB, pathologic T stage 1 or 2, clinically negative axillary lymph nodes, 1 or 2 metastatic axillary lymph nodes, no radiation therapy, and no neoadjuvant therapy. We divided the patients into the SLNB only and SLNB + ALND groups. The groups were matched by propensity scores. We retrospectively analyzed the differences in the overall survival (OS) between the 2 groups. @*Results@#A total of 883 patients were matched in a 1:4 ratio for the SLNB only and SLNB + ALND groups in the cohort from 1999 to 2014. There were no significant differences in OS between the 2 groups (P = 0.413). Subgroup analysis revealed a significant survival benefit in the SLNB + ALND group in the T2 subgroup (P = 0.013). @*Conclusion@#OS did not differ between the 2 groups in early breast cancer patients with 1 or 2 metastatic axillary lymph nodes who underwent TM. Omission of ALND may be considered in selected patients.

Trends in Risk-Reducing Mastectomy and Risk-Reducing SalpingoOophorectomy in Korean Carriers of the BRCA1/2 Mutation / 한국유방암학회지

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.