Long-term outcome in patients with nodal-positive breast cancer treated with sentinel lymph node biopsy alone after neoadjuvant chemotherapy.

PURPOSE: Sentinel lymph node biopsy (SLNB) has yet to be accepted as the standard staging procedure in node positive (cN1) breast cancer patients who had clinical complete response in the axilla (cN0) following neoadjuvant chemotherapy (NAC), due to the presumed high false negative rate associated with SLNB in such scenario. This study aimed to determine whether there is a significant difference in the axillary recurrence rate (ARR) and long-term survival in this group of patients, receiving SLNB alone versus axillary lymph node dissection (ALND). METHODS: A retrospective cohort of cN1 patients who were rendered cN0 by NAC from January 2014 to December 2018 were identified from the Asan Medical Center database. Patients' characteristics and outcomes were collected and analyzed. RESULTS: 902 cN1 patients treated with NAC and turned cN0 were identified. 477 (52.9%) patients achieved complete pathological response in the axilla (ypN0). At a median follow up of 65 months, ARR was 3.2% in the SLNB only group and 1.8% in the ALND group (p = 0.398). DFS and OS were significantly worse in patients with ALND as compared to patients with SLNB only (p = 0.011 and 0.047, respectively). We noted more patients in the ALND group had T3-4 tumor. In the subgroup analysis, we showed that in the T1-2 subgroup (n = 377), there was no statistically significant difference in DFS and OS (p = 0.242 and 0.671, respectively) between SLNB only and ALND group. CONCLUSION: Our findings suggest that cN1 patients who were converted to ypN0 following NAC may be safely treated with SLNB only.

Characteristics and risk factors of axillary lymph node metastasis of microinvasive breast cancer.

PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.

Comparison of long-term oncological outcomes after central lumpectomy versus nipple-sparing breast-conserving surgery for centrally located breast cancer: a propensity score-matched study.

PURPOSE: To compare the oncological safety of nipple-sparing breast-conserving surgery (BCS) versus central lumpectomy for centrally located breast cancer (CLBC). METHODS: Patients who underwent BCS for CLBC at Asan Medical Center from 2007 to 2018 were reviewed retrospectively. The oncological outcomes of nipple-sparing BCS (NS-BCS) and central lumpectomy were compared using univariate and multivariate Cox regression analyses and compared again after 1:1 propensity score matching (PSM). RESULTS: The study included 306 patients who underwent NS-BCS and 106 patients who underwent central lumpectomy (median follow-up: 111 months). On multivariate analysis, central lumpectomy had a lower risk of local recurrence compared to NS-BCS, albeit without statistical significance (HR 0.14, 95% CI 0.02-1.24; p = 0.077). There was no significant difference in the risk of death (HR 0.14, 95% CI 0.01-1.68, p = 0.12). After PSM, each group had 106 patients. The 5-year and 10-year local recurrence-free survival rates were 94.2% and 92.9% for NS-BCS, and 99.1% and 99.1% for central lumpectomy, respectively (p = 0.031). There were no significant differences in overall survival, regional recurrence-free survival, or distant recurrence-free survival. Fifteen patients (4.9%) who underwent NS-BCS had ipsilateral breast tumor recurrence (IBTR), of which 40% were in the nipple-areolar complex and previous surgical sites. One patient (0.9%) who underwent central lumpectomy experienced an IBTR in a different quadrant. CONCLUSION: NS-BCS showed more local recurrence than central lumpectomy. When deciding whether to spare the nipple during BCS in CLBC, patients should be sufficiently informed about the risk of IBTR.

Clinical significance of microinvasive breast cancer across the different subtypes and human epidermal growth factor receptor 2 expression levels.

PURPOSE: The clinical behavior, prognosis, and management of microinvasive breast cancer (MiBC) is controversial. We aimed to clarify its significance across different subtypes and the role of human epidermal growth factor receptor 2 (HER2) expression in MiBC. METHODS: We analyzed 1530 patients with T1mi (tumor size ≤ 0.1 cm), node-negative breast cancer who underwent breast conserving surgery or total mastectomy between 2001 and 2020 at the Asan Medical Center (AMC). RESULTS: When divided into four subtypes, hormone receptor (HR)+/HER2-, HR+ /HER2+ , HR-/HER2+ , and HR-/HER2-, HR-/HER2+ had the highest prevalence rate of 38.5% in MiBC patients. In a median follow-up period of 74 months (0-271 months), 103 (6.7%) patients had recurrent tumor, and 95 (6.2%) had local recurrence. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were worst in the HR-/HER2+ group. The five-year DFS for the HR-/HER2+ group was 92.2%, while it was 97.1% for the HR+/HER2- group (p = 0.024 The five-year LRFS for HER2- patients were better than that of HER2+ MiBC patients, which were 97.1 and 93.8%, respectively (p = 0.010). Univariate and multivariate Cox regression analyses showed that the HR-/HER2+ group had relatively higher risk of recurrence compared to the HR+/HER2- group (hazard ratio [HR] = 2.332, 95% confidence interval [CI] 1.412-3.852, p = 0.001 unadjusted; HR = 3.346, 95% CI 1.408-7.953, p = 0.006 adjusted). CONCLUSION: HER2 overexpression was significantly associated with adverse clinicopathologic parameters and increased local recurrence risk in MiBC. Therefore, more understanding of the clinical behavior of HER2 in MiBC will enable tailoring of adjuvant therapy for these patients.

Survival After Breast-Conserving Surgery Compared with that After Mastectomy in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Breast-conserving surgery (BCS) plus radiotherapy (BCS + RT) has been shown to improve survival compared with mastectomy in patients with early breast cancer; however, whether this superiority is maintained in breast cancer patients receiving neoadjuvant chemotherapy (NCT) is unclear. We evaluated and compared the survival outcomes after BCS + RT and mastectomy in Korean women with breast cancer treated with NCT. METHODS: We evaluated 1641 patients who received NCT before surgery (BCS or mastectomy). We performed propensity score matching to minimize potential bias due to factors other than the surgical method and compared the 5-year, disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates before and after exact matching. RESULTS: Among the 1641 patients, 839 (51.1%) underwent BCS + RT and 802 (48.9%) underwent mastectomy. Patients who underwent mastectomy had larger tumors and more frequently had positive nodes. For BCS+RT and mastectomy, the unadjusted 5-year DFS, 5-year DMFS, and 5-year OS rates were 87.0% and 73.1%, 89.5% and 77.0%, and 91.8% and 81.0%, respectively (all p < 0.05 = 0.000). After PSM, 5-year DFS, 5-year DMFS, and 5-year OS rates for BCS + RT and mastectomy were 87.6% and 69.1%, 89.7% and 76.0%, and 89.1% and 75.7%, respectively (all p < 0.05). In both unadjusted and adjusted analyses accounting for various confounding factors, BCS + RT was significantly associated with improved DFS (p < 0.05), DMFS (p < 0.05), and OS (p < 0.05) rates compared with mastectomy. CONCLUSIONS: BCS + RT does not impair DFS and OS in patients treated with NCT. Tumor biology and treatment response are significant prognostic indicators. Our results suggest that BCS + RT may be preferred in most breast cancer patients when both BCS and mastectomy are suitable.

Chemotherapy for ipsilateral breast tumor recurrence: a propensity score-matching study.

PURPOSE: We evaluated the benefit of chemotherapy in patients with ipsilateral breast tumor recurrence (IBTR) by comparing the survival outcomes between the chemotherapy and no chemotherapy groups, using propensity score matching (PSM), and analyze the survival outcomes stratified by hormone receptor status of IBTR. METHODS: We retrospectively analyzed patients who developed invasive IBTR after undergoing breast-conserving surgery at our institution between 1990 and 2013. A 1:1 PSM analysis was performed to compare the survival rates between the two study groups; additional analysis stratified by hormone receptor status was performed. The Kaplan-Meier method and Cox proportional hazards model were used to compare the second recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates between the two groups. RESULTS: The 217 IBTR patients had a median follow-up of 125.3 months. After PSM, patients without chemotherapy and with chemotherapy (n = 35 in both groups) were included. No significant differences were observed in the 10-year second RFS [50.2% without chemotherapy vs. 39.8% with chemotherapy, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.50-1.80], DMFS (85.4% vs. 70.3%, HR 1.51, 95% CI 0.66-3.44), and OS (81.6% vs. 68.6%, HR 1.73, 95% CI 0.76-3.90) rates between the two groups. Analyses stratified by hormone receptor status showed similar findings: no significant differences were observed in the second RFS, DMFS, and OS rates between the two groups in both hormone receptor-positive and -negative groups. CONCLUSION: Chemotherapy had no impact in the long-term survival outcomes of IBTR patients regardless of the hormone receptor status.

Clinical Course and Predictors of Subsequent Recurrence and Survival of Patients With Ipsilateral Breast Tumor Recurrence.

PURPOSE: To evaluate the clinical course and long-term outcomes of patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and identify independent prognostic factors for further recurrence. METHODS: In this retrospective study, we reviewed the records of 327 patients who experienced IBTR after undergoing BCS for breast cancer at Asan Medical Center during 1990-2013. Overall survival (OS) after IBTR and cumulative incidence rates of recurrences after IBTR were calculated. The association of clinicopathological factors with survival and the development of further recurrence after IBTR was determined in multivariate analysis. RESULTS: At a median follow-up of 127.7 months, 97 patients experienced recurrence after IBTR. The 5-year and 10-year cumulative incidence rates of recurrence after IBTR were 32% and 41%, respectively. The 5-year and 10-year OS rates after IBTR were 86.6% and 70.3%, respectively. In multivariate analysis, hormone receptor negativity was associated with decreases in OS after IBTR (hazard ratio [HR] 2.83, 95% confidence interval [CI] 1.18-6.78). Patients with longer disease-free interval (DFI) had decreased risks of second recurrence (HR .99, 95% CI .99-1.00), and second locoregional recurrence (LRR) (HR .98, 95% CI .97-.99). Lymphovascular invasion (LVI) of IBTR was associated with increased recurrence rates (second recurrence-free survival, HR 3.58, 95% CI 2.16-5.94; second LRR free survival, HR 5.21, 95% CI 2.77-9.78; second distant metastasis-free survival, 2.11, 95% CI 1.04-4.30) and lower survival rates (OS after IBTR, HR 4.64, 95% CI 2.23-9.67). CONCLUSIONS: Despite subsequent recurrences during long-term follow-up, the survival rates after IBTR remained high. Patients with hormone receptor-negative tumors, shorter DFI, and tumors that present LVI of IBTR had higher risks for recurrence and poor survival rates after IBTR. The study findings may help in understanding the course and prognosis of IBTR patients and identifying high-risk IBTR to establish management strategies.

Is There a Difference in the Diagnosis and Prognosis of Local Recurrence between Autologous Tissue and Implant-Based Breast Reconstruction?

Introduction: Breast reconstruction has become common after total mastectomy; however, certain types of breast reconstruction may be associated with delayed local recurrence or poor survival. Here, we investigated whether there are differences in the diagnosis and prognosis of local recurrence between autologous reconstruction and implant reconstruction. Materials and Methods: A retrospective analysis was performed on patients undergoing breast cancer surgery with autologous tissue or immediate implant reconstruction in a single center (January 2003-December 2017). Patient data including the period from cancer surgery to local recurrence diagnosis, tumor size at the time of recurrence, and survival time after cancer surgery and recurrence detection were analyzed. Results: There was a significant difference (p = 0.021) in the time from surgery to recurrence between the autologous tissue (1,246 days) and implant (909 days) groups. Recurrence tumor size did not differ (autologous: 1.00 cm2 vs. implant: 0.90 cm2; p = 0.813). Survival time after surgery (p = 0.63) and recurrence detection (p = 0.74) did not statistically significant. Conclusions: Statistical difference in the detection time was observed between autologous tissue and implant group. On the other hand, there is no difference in recurrence tumor size or survival time. A further study is necessary to identify the different detection time of local recurrence.

Clinicopathological characteristics and outcomes of malignant adenomyoepithelioma of the breast: a single institution's experience.

BACKGROUND: Malignant adenomyoepithelioma of the breast is a rare tumor and most of relevant literature consists of individual case reports. This study objective was designed to evaluate clinicopathological features and treatment outcomes of 15 cases of malignant adenomyoepithelioma at a single institute. METHODS: A retrospective medical record review was performed for 15 subjects confirmed with malignant adenomyoepithelioma upon postoperative pathological diagnosis at the Asan Medical Center from January 2008 to June 2018. Data regarding age at diagnosis, preoperative biopsy results, operation methods, the status of hormone receptors and HER2, and clinical outcomes were collected. RESULTS: All cases were female patients diagnosed at median age of 50 years. Preoperative core needle biopsy results showed that 40% of the cases (6 out of 15) were benign which was in discordance with the final malignant pathology report. Thirteen cases underwent wide excision with or without sentinel lymph node biopsy (SLNB) and 2 cases had total mastectomy with SLNB. Five of 11 cases (45.5%) were triple negative. Ten of 15 cases underwent postoperative radiation therapy, 3 cases underwent chemotherapy, and 5 cases underwent endocrine therapy. During median follow-up of 55 months, the 5-year overall survival rate was 87.5% and the 5-year disease free survival rate was 91.7%. Two lung metastases developed. One case showed local recurrence 3 years after surgery and radiotherapy and subsequently developed lung metastasis 1 year late. Another case developed lung metastasis one and a half years after surgery in combination with endocrine therapy and neoadjuvant chemotherapy. CONCLUSION: Preoperative core needle biopsy showed inaccurate results for diagnosing malignant adenomyoepithelioma. Malignant adenomyoepithelioma has a high rate of triple negative subtype but has a relatively good prognosis although there is a risk of local and systemic recurrence.

Comparison of survival outcomes for axillary surgery extent based on intraoperative sentinel lymph node biopsy result after neoadjuvant chemotherapy for breast cancer.

PURPOSE: To investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC). METHOD: We retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n = 188) and ALND (n = 295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups. RESULT: At a median follow-up of 59.4 months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.43-2.05, p = 0.876) and 5-year overall survival (97.7% vs. 97.3%, HR = 1.65, 95% CI = 0.58-4.65, p = 0.347) between the two groups. CONCLUSION: Our analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

Prognostic value of p53 expression in hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: The aim of this study was to determine whether the outcome to neoadjuvant chemotherapy (NAC) can be predicted by analyzing p53 expression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients. METHODS: We retrospectively reviewed 594 patients diagnosed with stage I-III HR-positive, HER2-negative breast cancer, and treated with NAC at the Asan Medical Center between 2008 and 2014. Expression of p53 was assessed, and overall survival (OS) and breast cancer-specific survival (BCSS) were investigated and compared between groups. RESULTS: At a median follow-up period of 69.8 months, OS and BCSS were higher in the p53-negative (p53(-)) group than in the p53-positive (p53(+)) group. Five-year OS was 95.4% in the p53(-) and 92.1% in the p53(+) group (p = 0.005). BCSS was 96.2% in the p53(-) group and 93% in the p53(+) group (p = 0.008). CONCLUSION: High expression of immunohistochemically detected p53 was strongly and significantly associated with decreased OS and BCSS than low p53 expression, suggesting that p53 may be a powerful prognostic factor in HR-positive, HER2-negative breast cancer patients receiving NAC.

Long-term survival outcomes of repeat lumpectomy for ipsilateral breast tumor recurrence: a propensity score-matched analysis.

PURPOSE: This study aimed to compare long-term survival outcomes of repeat lumpectomy with total mastectomy after ipsilateral breast tumor recurrence (IBTR) using propensity score matching (PSM). METHODS: We retrospectively analyzed patients with IBTR who had undergone initial breast-conserving surgery for breast cancer at our institution between January 1990 and December 2013. The Kaplan-Meier method and Cox proportional hazards model were used to compare survival rates between the two groups. PSM was performed using the following covariates: age at initial operation, initial T stage, N stage, hormone receptor status, human epidermal growth factor receptor 2 status, chemotherapy, radiotherapy, and IBTR tumor size. RESULTS: We enrolled 335 IBTR patients with a median follow-up of 126.6 months. No significant differences were observed in the 5-year overall survival (OS), breast cancer-specific survival (BCSS), OS after IBTR, and BCSS after IBTR and 10-year survival probability between the two groups in a multivariate analysis. After PSM, patients who had undergone repeat lumpectomy and total mastectomy (n = 90 in both groups) were included. No significant differences were observed in the 10-year OS (hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.49-2.39), BCSS (HR 0.83, 95% CI 0.35-1.95), OS after IBTR (HR 0.83, 95% CI 0.38-1.83), and BCSS after IBTR (HR 0.64, 95% CI 0.28-1.47) between the two groups. CONCLUSIONS: No significant differences were observed in survival outcomes between patients with IBTR who underwent repeat lumpectomy or total mastectomy. Our results can be helpful in selecting the appropriate surgical method for IBTR.

Survival of Breast-Conserving Surgery Plus Radiotherapy versus Total Mastectomy in Early Breast Cancer.

BACKGROUND: Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM. METHODS: In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database. RESULTS: In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392-1.707, p < 0.001) and 1.405 (95% CI 1.183-1.668, p < 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476-2.328, p < 0.001) and 1.807 (95% CI 1.186-2.752, p = 0.006), respectively. CONCLUSIONS: Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients.

Changes in bone mineral density during 5 years of adjuvant treatment in premenopausal breast cancer patients.

PURPOSE: Adjuvant treatment for breast cancer in postmenopausal women is a risk factor for bone loss. However, the association between bone mineral density (BMD) changes in premenopausal breast cancer patients and various adjuvant treatment regimens is not well characterized. In this study, we evaluated the changes in BMD according to adjuvant treatment in premenopausal women with breast cancer. METHODS: Between 2006 and 2010, BMD data of 910 premenopausal women with breast cancer before operation and 1, 2, 3.5, and 5 years post-operation were retrospectively analyzed. The patients were divided according to the type of treatment: observation (O), tamoxifen (T), chemotherapy (C), C followed by T (C → T), and gonadotropin-releasing hormone (GnRH) agonist with T (G + T). RESULTS: After 5 years of follow-up, BMD changes were similar between the T and O groups (all p > 0.05). Within 1 year of treatment, the C group showed the most significant BMD loss. The C → T and G + T groups showed more significant BMD loss in the lumbar spine and femur than the O and T groups (both p < 0.001, both). After 1 year of treatment, BMD loss in the lumbar spine was significantly greater in the C → T and G + T groups than in the T group; this tendency was maintained for 5 years of treatment (all p < 0.005). CONCLUSION: Premenopausal women who received adjuvant treatment which induced menopause showed significant bone loss which lasted for 5 years. Although no significant difference was observed between the O and T groups, tamoxifen treatment during chemotherapy or GnRH agonist treatment might prevent bone loss.

Risk stratification system for groups with a low, intermediate, and high risk of subsequent distant metastasis and death following isolated locoregional recurrence of breast cancer.

PURPOSE: This study aimed to identify prognostic factors for long-term outcomes among patients with isolated locoregional recurrence (ILRR) of breast cancer as their first failure event. Many prognostic tools have been developed to inform systemic treatment choices in the adjuvant setting, but tools for predicting post-ILRR prognosis are scarce. METHODS: A total of 495 patients who experienced ILRR after primary surgery at the Asan Medical Center between 1989 and 2008 were included. All patient information and tumor characteristics at the initial surgery were retrieved from our retrospectively collected database, and ILRRs were categorized as local recurrence or regional recurrence (RR). Distant metastasis-free survival (DMFS), breast cancer-specific survival (BCSS), and overall survival post-ILRR were calculated. RESULTS: The median follow-up from the ILRR was 65 months (range 1-249 months), and the 5-year post-ILRR DMFS rate was 58.9%. We found three factors-lymph node metastasis, a disease-free interval < 30 months, and RR as the ILRR type-that were independent prognostic factors for both DMFS [hazard ratio (HR) = 2.08, 1.60, and 1.59; P < 0.001, 0.002, and 0.003, respectively] and BCSS (HR = 2.28, 1.99, and 1.48; P < 0.001, < 0.001, and 0.016, respectively) post-ILRR. Patients were classified into four groups according to the presence these three prognostic indicators: the low-, intermediate-, high-, and extremely high-risk groups. The 5-year post-ILRR DMFS rates were 79.4%, 68.1%, 47.6%, and 36.0%, respectively. CONCLUSIONS: This risk stratification system for subsequent distant metastases after ILRR can be used to make more informed decisions regarding prognosis-based local or systemic management strategies.

Diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study.

BACKGROUND: A biopsy of first recurrence or metastatic disease is recommended to re-evaluate oestrogen receptor status in patients with breast cancer and to select appropriate treatment. However, retesting for oestrogen receptor status with rebiopsy is not always feasible, depending on lesion location and the risk associated with biopsy, and in these cases clinicians continue to treat patients according to the oestrogen receptor status of the primary tumour. Consequently suboptimal therapy might be offered to these patients. We assessed the diagnostic accuracy and safety of 16α-[18F]fluoro-17ß-oestradiol (18F-FES) PET-CT to assess oestrogen receptor status in patients with recurrent or metastatic breast cancer. METHODS: We did a prospective cohort study at the Asan Medical Center, Seoul, South Korea. Eligible patients had breast cancer, with first recurrence or metastatic disease at presentation, were 19 years or older, and had an Eastern Cooperative Oncology Group performance status of 0-2. The primary objective was to show the agreement between qualitative 18F-FES PET-CT interpretation and the results of oestrogen receptor expression by immunohistochemical assay, a non-reference standard test. Whole-body 18F-FES PET-CT imaging was done after intravenous injection of 111-222 MBq of 18F-FES, with dosing primarily determined by radiation dosimetry analysis. 18F-FES uptake above background intensity was interpreted as positive. Efficacy was assessed in all patients with histologically confirmed recurrent or metastatic breast cancer who received 18F-FES and had PET-CT images available (intention-to-diagnose analysis), and safety was assessed in all patients who received 18F-FES. This study is registered with ClinicalTrials.gov, number NCT01986569. FINDINGS: Between Nov 27, 2013, and Nov 10, 2016, 93 patients were enrolled. Of the 85 patients included in the efficacy analysis, 47 (55%) were oestrogen receptor-positive and 38 (45%) were oestrogen receptor-negative. Positive status percent agreement between the 18F-FES PET-CT results and oestrogen receptor status by immunohistochemical assay was 76·6% (95% CI 62·0-87·7) and the negative status percent agreement was 100·0% (90·8-100·0). Patients who were oestrogen receptor-positive and had a positive 18F-FES PET-CT result had a significantly higher progesterone receptor expression than those who were oestrogen receptor-positive and had a negative 18F-FES PET-CT result (23 [68%] of 34 patients vs 0 of 11 patients; p<0·0001). The most common adverse event was procedural pain in nine (10%) of 90 patients injected with 18F-FES. No adverse events were related to the study drug except injection site pain in one (1%) patient. No serious adverse events were recorded. INTERPRETATION: The high negative percent agreement between 18F-FES PET-CT and oestrogen receptor status by immunohistochemical assay in this cohort suggests that positive 18F-FES uptake by recurrent or metastatic oestrogen receptor-positive breast cancer lesions could be an alternative to oestrogen receptor assays in this setting. Staging assessment should include 18F-FES PET-CT when retesting oestrogen receptor status is not feasible. FUNDING: Asan Institute for Life Sciences, Ministry of Health and Welfare, South Korea.

Age-related risk factors associated with primary contralateral breast cancer among younger women versus older women.

PURPOSE: Contralateral prophylactic mastectomy is increasing, despite unclear evidence of improving survival. To investigate the age-related risk factors for contralateral breast cancer (CBC). METHODS: This study included 8716 patients diagnosed with non-metastatic unilateral invasive breast cancer between 1989 and 2008. Data on primary tumor size, node metastasis, grade and subtype using individual matching were used to adjust for differences in the primary tumor and treatment between younger and older age groups. CBC risk factors, CBC-free survival, and annual CBC risk were analyzed by age. RESULTS: The younger group included 652 patients aged under 35 years, and the older group included 2608 women aged 35 years or older. The median time to CBC development was 6.1 years. CBC was detected in 6.6% of the women in the younger group and 2.5% of those in the older group. Multivariable analysis revealed a relative CBC risk of 2.48 in younger women compared to older women. The risk was significantly higher among women with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors (hazard ratio [HR] 4.98), a family history of breast cancer (HR 7.79), and anti-hormone therapy (HR 3.46). In younger women with HER2-positive cancer, CBC occurrence peaked at 4.6 years after surgery, in those with hormone receptor-positive cancer, it peaked at 7.1 years after surgery, and in triple-negative disease cases, and it increased steadily over time. CONCLUSIONS: After adjusting for primary breast tumor characteristics, patients < 35 years old had 2.5 times the risk of CBC development compared to the older women. CBC occurrence peaked within 5 years after primary breast cancer in younger women with the HER2-positive subtype and after 5 years in cases with the hormone receptor-positive subtype.

Clinical Implication of HER2 Status in Hormone Receptor-Positive Mucinous Breast Cancer.

PURPOSE: Mucinous carcinoma (MC) is a rare breast cancer with favorable outcome. Unlike typical breast cancer, the current guidelines do not recommend chemotherapy or anti-human epidermal growth factor receptor 2 (HER2) therapy for hormone receptor (HR)-positive MC, regardless of HER2 status. We evaluated the prognostic implication of HER2 status in HR-positive MC. METHODS: We retrospectively reviewed the data of 471 patients with pure MC (stages I-III) who underwent curative surgery. We analyzed 5-year disease-free survival (DFS) and distant metastasis-free survival (DMFS), according to clinicopathological characteristics. RESULTS: The median follow-up duration was 79.0 months. Overall, the 5-year DFS rate was 95.7% and the 5-year DMFS rate was 96.2%. Nodal status was the only significant factor for DFS (relative risk [RR], 3.40; 95% confidence interval [CI] 3.40-9.67, p = 0.021). Among HR-positive/node-negative patients with tumor size ≥ 3 cm, HER2-positive patients showed significantly worse DFS (RR, 8.76; 95% CI 1.45-52.76, p = 0.018) and DMFS (RR, 11.37; 95% CI 1.37-74.70, p = 0.011). This finding was consistently significant, when combining both "HR-positive/node-negative/tumor size ≥ 3 cm" and "HR-positive/node-positive" MC (n = 125) for DFS (RR, 4.30; 95% CI 1.43-12.97, p = 0.009) and DMFS (RR, 4.93; 95% CI 1.63-14.90, p = 0.005). Intriguingly, within this subgroup, among HER2-positive tumors, whereas 5-year DFS was 60.2% in patients who did not receive trastuzumab, 100% of those who received trastuzumab were disease free (p = 0.053). CONCLUSIONS: In HR-positive, node-negative MC with tumor size ≥ 3 cm, patients with HER2-positive MC showed worse survival, suggesting a potential role of an anti-HER2 strategy in this subgroup.

Characteristics and prognosis of breast cancer after liver or kidney transplantation.

PURPOSE: Immunoediting is crucial in cancer development and progression. This study compared the characteristics and prognosis of post-transplant breast cancer (PTBC) patients receiving immunosuppressants and general breast cancer patients. METHODS: Data from the Asan Medical Center Breast Cancer (AMCBC), kidney transplantation, and liver transplantation databases recorded during 1989-2013 were retrospectively analyzed. Four controls of AMCBC cohort per one case of PTBC cohort were selected based on tumor size, lymph node metastasis, and age. RESULTS: After a median of 61 and 90.8 months after liver and kidney transplantation, respectively, 8 and 16 patients were diagnosed with breast cancer, respectively (p = 0.178). Mean age at breast cancer diagnosis was 51.9 (±8.7) and 45.2 (±4.5) years in liver and kidney transplantation patients, respectively. Age at diagnosis was significantly younger in kidney transplantation patients than in general breast cancer patients (45.2 ± 4.5 vs. 48.5 ± 10.1 years; p = 0.008). Cancer was detected via asymptomatic screening in 41.7% of the PTBC cohort but 30.6% of the control cohort (p = 0.241). In the PTBC cohort, 7 (29.2%) patients had stage 0 breast cancer compared with 1704 (9.7%) in the control cohort (p = 0.022); 22 (91.7%) patients had lymph node-negative cancer compared with 11,704 (66.8%) in the control cohort (p = 0.01). Estrogen receptor, progesterone receptor, and HER2 positivity did not differ between cohorts. Immunosuppressant use was not a poor prognostic factor for breast cancer patients. CONCLUSIONS: Age at breast cancer diagnosis was younger in patients who received kidney transplants; the subtype and prognosis of breast cancer were comparable with that in the general cohort. Immunosuppressants do not adversely affect breast cancer prognosis.

A retrospective prognostic evaluation analysis using the 8th edition of the American Joint Committee on Cancer staging system for breast cancer.

PURPOSE: Breast cancer is a group of diseases with different intrinsic molecular subtypes. However, anatomic staging alone is insufficient to determine prognosis. The present study analyzed the prognostic value of the American Joint Committee for Cancer (AJCC) 8th edition cancer staging system. METHODS: This retrospective, single-center study included breast cancer cases diagnosed from January 1999 to December 2008. We restaged patients based on the 8th edition AJCC cancer staging system and analyzed the prognostic value of the anatomic and prognostic staged groups. Follow-up data including disease-free survival (DFS), overall survival (OS), and clinic-pathological data were collected to analyze the differences between the two staging subgroups. RESULTS: The study enrolled 7458 breast cancer patients with a 98.7-month median follow-up. Both the 5-year DFS and OS were significantly different between the anatomic and prognostic staged groups. The 5-year OS according to disease subtype was as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR(+)/HER2(-)], 90.9%; HR(+)/HER2(+), 84.7%; HR(-)/HER2(+), 81.1%; and HR(-)/HER2(-), 80.9%. According to the anatomic stage, the 5-year OS of patients with stage III HR(+)/HER2(-) disease was superior to that of patients with stage II HR(-)/HER2(-) disease (88.3 vs. 86.5%). Per the prognostic stage, both the 5-year DFS and OS rates of patients with stage II HR(-)/HER2(-) disease were higher than those of patients with stage III HR(+)/HER2(-) disease (90.1 and 94.3% vs. 79.1 and 88.9%). CONCLUSIONS: The prognostic staging system is a refined version of the anatomic staging system and encourages a more personalized approach to breast cancer treatment.