Endoxifen Concentration is Associated with Recurrence-Free Survival in Hormone-Sensitive Breast Cancer Patients.

Purpose: The metabolism of tamoxifen is influenced by various cytochrome p450 enzymes, including CYP2D6 and CYP2C19, leading to variations in the levels of endoxifen, even with the same tamoxifen dosage. However, the clinical significance of endoxifen on the prognosis of breast cancer patients remains controversial. This study aimed to elucidate the relevance of endoxifen level to recurrence-free survival censored with tamoxifen discontinuation (RFSt), representing the RFS for tamoxifen itself, of breast cancer patients and determine a suitable cutoff for prognostication. Materials and Methods: The study included 478 breast cancer patients, and tamoxifen and its metabolites, including endoxifen, were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). An optimal cutoff was determined with maximally selected rank statistics. Survival analysis and Cox regression were conducted based on this cutoff. Results: An endoxifen level of 21.00 ng/mL was the optimal cutoff for prognostication. Survival analysis revealed a statistically significant difference in RFSt between the low endoxifen group (≤ 21.00 ng/mL) and high endoxifen group (> 21.00 ng/mL) (log-rank test, p=0.032). The 10-year probability of RFSt was 83.2% (95% CI, 77.0-89.9%) and 88.3% (95% CI, 83.3-93.5%) in the low and high endoxifen groups, respectively. Multivariable Cox proportional hazards regression indicated endoxifen concentration as a significant factor affecting prognosis, which was adjusted with other clinical characteristics. Conclusion: Endoxifen could serve as a marker for appropriate tamoxifen treatment, and an endoxifen cutoff of 21.00 ng/mL could be advantageous in prognostication. Based on this cutoff, therapeutic drug monitoring would benefit patients displaying a suboptimal concentration.

The Effects of National Insurance Coverage Expansion and Genetic Counseling's Role on BRCA1/2 Mutation Tests in Breast Cancer Patients.

PURPOSE: This study aims to evaluate the impact of South Korea's national insurance coverage (NIC) expansion and the addition of genetic counselors on BRCA1/2 mutation testing rates in breast cancer patients. MATERIALS AND METHODS: A retrospective review was conducted at the Samsung Medical Center (SMC), dividing patients into three groups: pre-NIC expansion, post-NIC expansion, and post-extra genetic counselor involvement. The number of BRCA1/2 tests performed and the detection rates among newly diagnosed and follow-up patients, particularly focusing on triple-negative breast cancer (TNBC) cases, were analyzed. RESULTS: Post-NIC expansion, there was a significant increase in BRCA1/2 testing rates, with a gradual rise in detection rates while maintaining statistical significance. TNBC patients under 60 experienced substantial increases in testing rates. The number of follow-up patients recalled for testing also rose significantly after the extra genetic counselor involvement. Additionally, NIC expansion increased insurance coverage for TNBC patients, enhancing accessibility to testing. CONCLUSION: The study highlights the positive impact of NIC expansion and genetic counselor involvement on BRCA1/2 mutation testing rates and subsequent patient management. Addressing financial barriers to testing and incorporating genetic counseling significantly improve patient outcomes. This model provides a potential strategy for enhancing early detection and personalized treatment for breast cancer patients with BRCA1/2 mutations, contributing to global cancer management efforts.

A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer.

Purpose: Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies. Materials and Methods: In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing. Results: By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor ß diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores. Conclusion: Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations.

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10-20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3-152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Comprehensive Young Age Breast Cancer registry from clinical, genomics, and patient-reported outcomes measured with 15 years follow-up: the CHARM cohort profile.

BACKGROUND: In recognition of the distinct clinical challenges and research gaps in young breast cancer (YBC) patients, we established the Comprehensive Young Age Breast Cancer (CHARM) registry to collect prospective data. METHODS: This prospective cohort included patients who were newly diagnosed with histologically confirmed breast cancer without prior treatment at the Samsung Medical Center (SMC) in April 2013. We included patients who were either 40 years old or younger at the time of diagnosis, pregnant at breast cancer diagnosis or diagnosed with breast cancer within 1 year of delivery. All data were collected using Medidata's Rave Electronic Data. Clinical data were obtained from electronic medical records. Two experienced pathologists reviewed the pathologic data. Bone mineral densitometry tests have been conducted annually. To obtain multi-omics data, tumor tissues and blood samples were prospectively collected from consenting patients in the registry during surgery. The fertility-related factor also collected collaborated with the Department of Obstetrics and Gynecology. Anti-Müllerian hormone, estradiol, follicle-stimulating hormone, and luteinizing hormone levels were measured using an additional blood sample from baseline to last follow-up. Patient-reported outcomes were assessed using mobile questionnaires. RESULTS: A total of 1868 participants were included in the SMC YBC study. The average (standard deviation) age was 35.57 (3.79) and 99.8% of the participants were premenopausal. Among them, 1062 participants completed the PRO questionnaires. CONCLUSIONS: The SMC YBC cohort serves as a comprehensive registry for YBC to optimize care and improve knowledge regarding the management of YBC.

Outcomes of whole breast radiation therapy in Asian breast cancer patients with prior cosmetic implants.

BACKGROUND: As breast augmentation has become more popular, an increasing number of women with augmented breasts require treatment for breast cancer. This study aimed to assess the outcomes of postoperative whole breast radiation therapy (WB-RT) in Asian patients with breast cancer who underwent prior cosmetic breast implantation. METHODS: We retrospectively reviewed the medical records of 61 patients with breast cancer who had prior cosmetic breast implants (prior-CBI) and underwent breast-conserving surgery (BCS) and WB-RT between 2015 and 2020. The median implant volume was 238.8 cc, with a median interval of 84.7 months between the prior-CBI and BCS. WB-RT was administered with either conventional fractionation (CF-RT) at 50 Gy in 25 fractions (N = 36) or hypofractionation (HF-RT) at 42.6 Gy in 16 fractions (N = 25). The incidences of implant-related complications (IRC) and their contributing factors were analyzed. RESULTS: After a median follow-up of 43.5 months, the 3-year cumulative incidences of IRC and implant loss were 17.2% and 4.9%, respectively. Among the four (6.6%) patients who opted for implant removal after RT, three were potentially related to RT-related capsular contracture. There was no difference in the 3-year cumulative IRC rates following CF-RT and HF-RT (12.2% and 26.7%, respectively; p = 0.120). The risk factors for IRC included a larger implant size (> 260 cc) and a higher ratio of breast tissue to implant volume. CONCLUSIONS: This study demonstrated a favorable safety profile of WB-RT for treatment of breast cancer in Asian women with prior-CBI. The integration of HF-RT following BCS was thought to be a feasible approach.

Oncologic Outcomes of Immediate Breast Reconstruction in the Setting of Neoadjuvant Chemotherapy: A Long-term Follow-up Study of a Matched Cohort.

PURPOSE: Despite the increasing use of immediate breast reconstruction (IBR), its oncologic safety in the setting of neoadjuvant chemotherapy (NACT) needs to be comprehensively clarified in breast cancer management. The objective of the present study was to analyze the oncologic safety of IBR following NACT. METHODS: In total, 587 patients with breast cancer who underwent a total mastectomy (TM) with IBR after NACT between 2008 and 2017 at a single institution were retrospectively reviewed. The reviewed patients with IBR following skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) were matched 1:3 to patients who underwent TM alone after NACT. Matching variables included age, clinical T and N stages before NACT, response to NACT, pathologic T and N stages, and molecular subtypes. RESULTS: After propensity score matching, 95 patients who underwent IBR following SSM/NSM after NACT (IBR group) and 228 patients who underwent TM alone after NACT (TM group) were selected. The median follow-up period was 73 (range, 5-181) months after matching. After matching, there were no significant differences between the two groups in 5-year locoregional recurrence-free survival (88.8% vs. 91.2%, p = 0.516), disease-free survival (67.3% vs. 76.6%, p = 0.099), distant metastasis-free survival (71.9% vs. 81.9%, p = 0.057), or overall survival (84.1% vs. 91.5, p = 0.061) rates. In multivariate analyses, conducting IBR was not associated with increased risks for locoregional recurrence, any recurrence, distant metastasis, or overall death. CONCLUSION: Our findings suggest that IBR following SSM/NSM elicits comparable long-term oncologic outcomes to those of TM alone in the setting of NACT.

Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study.

PURPOSE: We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. MATERIALS AND METHODS: Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. RESULTS: The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. CONCLUSION: In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

The Impact of HER2-Low Expression on Oncologic Outcomes in Hormone Receptor-Positive Breast Cancer.

Breast cancer is a prevalent malignancy with increasing incidence, particularly in Asian countries. Classification based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is pivotal in determining treatment. Recent advances have challenged the traditional dichotomy in HER2 classification, prompting investigation into the HER2-low subtype's characteristics and outcomes. This retrospective study analyzed 10,186 non-metastatic hormone receptor (HR)-positive, HER2-negative breast cancer cases treated from 2008 to 2020. Data encompassed clinical, pathological, and treatment information. Oncologic outcomes included disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS). In total, 56.5% were HER2-low cases. Differences in patient characteristics were noted, with more BRCA1/2 mutations and higher mastectomy rates in the HER2-low group (p = 0.002, p < 0.001, respectively). Fewer received adjuvant chemotherapy or radiation therapy, and fewer histologic and nuclear grade 1 tumors were identified (all p < 0.001). With a median follow-up of 64 months (range: 13-174), HER2-low cases exhibited better DFS, OS, and BCSS than HER2-0 cases (p = 0.012, p = 0.013, and p = 0.013, respectively). Notably, the prognosis differed between premenopausal and postmenopausal subgroups, with BCSS benefitting premenopausal patients (p = 0.047) and DFS and OS benefitting postmenopausal patients in the HER2-low group (p = 0.004, p = 0.009, respectively). Multivariate analysis confirmed HER2 status as an independent predictor of these outcomes (p = 0.010, p = 0.008, and p = 0.014, respectively). This extensive single-center study elucidates the favorable prognosis associated with HER2-low status in HR-positive breast cancer. However, this effect differs among premenopausal and postmenopausal patients, necessitating further research into the underlying tumor biology.

Benefit of postoperative regional nodal irradiation in patients receiving preoperative systemic therapy with docetaxel/carboplatin/trastuzumab/pertuzumab for HER2-positive breast cancer.

AIM: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. METHODS: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. RESULTS: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. CONCLUSION: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

The Role of Post-Mastectomy Radiotherapy in T1-2N1 Breast Cancer Patients: Propensity Score Matched Analysis.

This study aimed to evaluate the role of post-mastectomy radiotherapy (PMRT) in T1-2N1 breast cancer. Between 2006 and 2014, a total of 504 patients with T1-2N1 breast cancer were analyzed. PMRT was administered to 71 patients, and 1:2 propensity score matching (PSM) was performed between the PMRT and non-PMRT groups. Loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) rates were compared according to PMRT status. Thirteen and one loco-regional recurrences were observed in the PMRT and non-PMRT groups, respectively. Before PSM, the 8-year LRC, DFS, and OS rates in the non-PMRT and PMRT groups were 98.5% and 96.5% (p = 0.426), 89.7% and 91.2% (p = 0.700), and 91.5% and 92.1% (p = 0.679), respectively. Corresponding rates were 95.6% and 96.5% (p = 0.365), 84.1% and 91.2% (p = 0.185), and 88.4% and 92.1% (p = 0.276), respectively, after PSM. Multivariate analysis showed that three lymph node metastases were prognostic for LRC and DFS rates and LVI for OS rate. Arm lymphedema developed in 32.4% of patients who received PMRT, which was significantly higher than the non-PMRT group (p < 0.001). Contributions of PMRT for improvement of treatments outcomes in T1-2N1 breast cancer patients were not evident, while the incidence of arm lymphedema significantly increased after PMRT. Further prospective trials are required to re-evaluate the role of PMRT.

Incidence of and Influencing Factors for Arm Lymphedema After Salvage Treatment for an Isolated Locoregional Recurrence of Breast Cancer.

PURPOSE: Data on subsequent arm lymphedema (SAL) after salvage treatment for locoregional recurrence (LRR) of breast cancer are limited. We conducted a study to evaluate the risk of SAL in patients with LRR. METHODS: We reviewed the data of patients with breast cancer who had LRR and were initially diagnosed between January 2003 and December 2017. Among the 214 patients who received curative salvage treatment, most had local (n = 125, 57.9%), followed by regional (n = 73, 34.1%), and locoregional (n = 16, 7.9%) recurrences. A competing risk analysis considering the factors of death and a second LRR were performed to exclude potential malignant lymphedema. We used the Fine-Gray subdistribution hazards model to estimate the hazard ratio (HR) for comparing the risk of SAL. RESULTS: With a median follow-up duration of 41.4 months (interquartile range, 25.6-65.1), 51 patients (23.8%) experienced SAL with a median interval of 9.9 months after treatment. The two-year cumulative incidence of SAL was 12.7%. Among the 18 patients with initial lymphedema, nine (50.0%) developed SAL. Multivariate analysis revealed that a history of lymphedema (HR, 4.61; p < 0.001) and taxane-based salvage chemotherapy (HR, 2.38; p = 0.009) were significantly associated with SAL development. CONCLUSION: Salvage treatment for LRR-induced SAL was performed in 24% of the patients. A history of initial lymphedema and salvage taxane-based chemotherapy increases the risk of developing SAL. Therefore, close surveillance for the incidence of SAL is required in patients opting for salvage treatment for LRR.

Risk factors of breast cancer recurrence in pathologic complete response achieved by patients following neoadjuvant chemotherapy: a single-center retrospective study.

Objective: Pathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR. Methods: This study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study. Results: In total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073). Conclusion: Results in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

Pretreatment endocrine symptoms and recurrence-free survival among young premenopausal patients with breast cancer: a prospective cohort study.

Background: Pretreatment endocrine symptoms in premenopausal patients might be considered as a potential marker of poor prognosis. We conducted a cohort study to evaluate the association between endocrine symptoms prior to treatment and recurrence-free survival (RFS) among premenopausal patients with breast cancer aged ⩽40 years. Methods: Data were obtained from a prospective cohort study (NCT03131089) conducted at the Samsung Medical Center from 2013 to 2021. We included patients aged ⩽40 years who had been diagnosed with breast cancer. The primary outcome measure was RFS. Endocrine symptoms were measured using the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES). We also calculated the hazard ratio (HR) for recurrence or all-cause mortality by comparing the tertiles of the FACT-ES score at diagnosis. Results: Among the 977 participants, the mean (standard deviation) age was 35.3 (3.9) years. At diagnosis, 17.2% of the patients had at least one severe endocrine symptom. During 3512 person-years of follow-up, the high symptom group had a worse RFS than the low-symptom group [HR = 2.05; 95% confidence interval (CI) = 1.19-3.54]. In particular, hot flashes (HR = 5.59; 95% CI = 1.96-15.93) and breast sensitivity (HR = 1.82; 95% CI = 1.00-3.32) were associated with reduced RFS. Conclusion: Close monitoring of pretreatment endocrine symptoms may be important in patients diagnosed with breast cancer at a young age.

Progesterone Receptor Expression Level Predicts Prognosis of Estrogen Receptor-Positive/HER2-Negative Young Breast Cancer: A Single-Center Prospective Cohort Study.

BACKGROUND: Although estrogen receptor (ER) expression levels affect the prognosis of breast cancer, studies about progesterone receptor (PR) expression levels are insufficient, especially in young breast cancer (YBC). The purpose of this study was to compare clinical characteristics and prognosis according to PR expression levels in invasive breast cancer patients. METHODS: A prospective cohort study was conducted to identify YBC patients with invasive carcinoma diagnosed at an age of less than 40 years old between 2013 and 2018. Clinicopathologic features and prognosis of ER-positive and human epidermal growth factor receptor 2 (HER2)-negative patients were investigated. Patients were stratified into strong PR (PR-positive cell proportion > 10%), low PR (PR-positive cell proportion = 1~10%), and PR-negative (PR-positive cell proportion < 1%). RESULTS: Among 458 patients enrolled, 386 (84.3%), 26 (5.7%), and 46 (10.0%) were categorized into strong PR, low PR, and PR-negative groups, respectively. The median follow-up duration was 58.6 months. Compared with the strong PR group, low PR and PR-negative groups were more likely to have high Ki-67 and a high nuclear grade. Low R and PR-negative groups had significantly worse disease-free survival (DFS) and distant metastasis-free survival (DMFS) than the strong PR group (p = 0.0033, p = 0007). Low PR group had an even higher risk of distant metastasis than PR-negative patients. Low PR patients and PR-negative had significantly lower overall survival (OS) rates than strong PR. CONCLUSION: Low PR might be a prognostic factor of ER-positive/HER2-negative in YBC.

Trends of axillary surgery in breast cancer patients with axillary lymph node metastasis: a comprehensive single-center retrospective study.

Purpose: Based on the results of previous trials, de-escalation of axillary surgery after neoadjuvant chemotherapy (NAC) has increased in patients with axillary lymph node (ALN) metastasis at presentation. This study aimed to review the trends of axillary surgery by time period and molecular subtype in patients with ALN metastasis. Methods: We analyzed the rates of sentinel lymph node biopsy (SLNB) and ALN dissection (ALND) based on time period and subtype. The time period was divided into 3 subperiods to determine the rate of axillary surgery type over time (period 1, from 2009 to 2012; period 2, from 2013 to 2016; and period 3, from 2017 to July 2019). Results: From 2009 to July 2019, 2,525 breast cancer patients underwent surgery. Based on subtype, the ALND rate of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease decreased by 13.0% from period 1 to period 3 (period 1, 99.4%; period 2, 97.5%; and period 3, 86.4%; P < 0.001). Conversely, the ALND rate in HR+/HER2+, HR-/HER2+, and triple-negative breast cancer (TNBC) significantly decreased by 43.7%, 48.8%, and 35.2% in period 1, period 2, and period 3, respectively (P < 0.001). In the patient group receiving NAC, HR+/HER2- had a significantly higher ALND rate (84.1%) than HR+/HER2+, HR-/HER2+, and TNBC (60.8%, 62.3%, and 70.7%, respectively; P < 0.001). Conclusion: The SLNB rate in patients with ALN metastasis has increased over time. However, the ALND rate in HR+/HER2- was significantly higher than in other subtypes.

Prediction Model for Postoperative Quality of Life Among Breast Cancer Survivors Along the Survivorship Trajectory From Pretreatment to 5 Years: Machine Learning-Based Analysis.

BACKGROUND: Breast cancer is the most common cancer and the most common cause of cancer death in women. Although survival rates have improved, unmet psychosocial needs remain challenging because the quality of life (QoL) and QoL-related factors change over time. In addition, traditional statistical models have limitations in identifying factors associated with QoL over time, particularly concerning the physical, psychological, economic, spiritual, and social dimensions. OBJECTIVE: This study aimed to identify patient-centered factors associated with QoL among patients with breast cancer using a machine learning (ML) algorithm to analyze data collected along different survivorship trajectories. METHODS: The study used 2 data sets. The first data set was the cross-sectional survey data from the Breast Cancer Information Grand Round for Survivorship (BIG-S) study, which recruited consecutive breast cancer survivors who visited the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, between 2018 and 2019. The second data set was the longitudinal cohort data from the Beauty Education for Distressed Breast Cancer (BEST) cohort study, which was conducted at 2 university-based cancer hospitals in Seoul, Korea, between 2011 and 2016. QoL was measured using European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 questionnaire. Feature importance was interpreted using Shapley Additive Explanations (SHAP). The final model was selected based on the highest mean area under the receiver operating characteristic curve (AUC). The analyses were performed using the Python 3.7 programming environment (Python Software Foundation). RESULTS: The study included 6265 breast cancer survivors in the training data set and 432 patients in the validation set. The mean age was 50.6 (SD 8.66) years and 46.8% (n=2004) had stage 1 cancer. In the training data set, 48.3% (n=3026) of survivors had poor QoL. The study developed ML models for QoL prediction based on 6 algorithms. Performance was good for all survival trajectories: overall (AUC 0.823), baseline (AUC 0.835), within 1 year (AUC 0.860), between 2 and 3 years (AUC 0.808), between 3 and 4 years (AUC 0.820), and between 4 and 5 years (AUC 0.826). Emotional and physical functions were the most important features before surgery and within 1 year after surgery, respectively. Fatigue was the most important feature between 1 and 4 years. Despite the survival period, hopefulness was the most influential feature on QoL. External validation of the models showed good performance with AUCs between 0.770 and 0.862. CONCLUSIONS: The study identified important factors associated with QoL among breast cancer survivors across different survival trajectories. Understanding the changing trends of these factors could help to intervene more precisely and timely, and potentially prevent or alleviate QoL-related issues for patients. The good performance of our ML models in both training and external validation sets suggests the potential use of this approach in identifying patient-centered factors and improving survivorship care.

A Survey of Practice Patterns for Clinical Nodal Staging Prior to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The importance of clinical staging in breast cancer has increased owing to the wide use of neoadjuvant systemic therapy (NST). This study aimed to investigate the current practice patterns regarding clinical nodal staging in breast cancer in real-world settings. MATERIALS AND METHODS: A web-based survey was administered to board-certified oncologists in Korea, including breast surgical, medical, and radiation oncologists, from January to April 2022. The survey included 19 general questions and 4 case-based questions. RESULTS: In total, 122 oncologists (45 radiation, 44 surgical, and 33 medical oncologists) completed the survey. Among them, 108 (88%) responded that clinical staging before NST was primarily performed by breast surgeons. All the respondents referred to imaging studies during nodal staging. Overall, 64 (52.5%) responders determined the stage strictly based on the radiology reports, whereas 58 (47.5%) made their own decision while noting radiology reports. Of those who made their own decisions, 88% referred to the number or size of the suspicious node. Of the 75 respondents involved in prescribing regimens for neoadjuvant chemotherapy, 58 (77.3%) responded that the reimbursement regulations in the selection of NST regimens affected nodal staging in clinical practice. In the case-based questions, high variability was observed among the clinicians in the same cases. CONCLUSIONS: Diverse assessments by specialists owing to the lack of a clear, harmonized staging system for the clinical nodal staging of breast cancer can lead to diverse practice patterns. Thus, practical, harmonized, and objective methods for clinical nodal staging and for the outcomes of post-NST response are warranted for appropriate treatment decisions and accurate outcome evaluation.

Impact of Adjuvant Hormone Therapy on Sleep, Physical Activity, and Quality of Life in Premenopausal Breast Cancer: 12-Month Observational Study.

PURPOSE: This study aimed to investigate the differences in sleep disturbance changes between patients receiving two hormone therapies ("tamoxifen plus ovarian function suppression group [T+OFS group]" versus "tamoxifen group [T group]") and the chronological changes in sleep disturbances in each group. METHODS: Premenopausal women with unilateral breast cancer who underwent surgery and were scheduled to receive hormone therapy (HT) with tamoxifen alone or with tamoxifen plus gonadotropin-releasing hormone (GnRH) agonist for ovarian function suppression were included. The enrolled patients wore an actigraphy watch for two weeks and completed questionnaires (insomnia, sleep quality, physical activity [PA], and quality of life [QOL]) at five time points: immediately before HT and 2, 5, 8, and 11 months after HT. RESULTS: Among the 39 enrolled patients (21 and 18 patients in the T+OFS group and T group, respectively), 25 (17 and 8 patients in the T+OFS group and T group, respectively) were finally analyzed. There were no differences between the two groups in time-dependent changes in insomnia, sleep quality, total sleep time, rapid eye movement sleep rate, QOL, and PA; however, the severity of hot flashes was significantly higher in the T+OFS group than in the T group. Although the interaction between group and time was not significant, insomnia and sleep quality significantly worsened at 2-5 months of HT when changes over time were analyzed within the T+OFS group. In both the groups, PA and QOL were maintained without significant changes. CONCLUSION: Unlike tamoxifen alone, tamoxifen plus GnRH agonist initially worsened insomnia and sleep quality, but gradually improved with long-term follow-up. Patients who initially experience insomnia during tamoxifen plus GnRH agonist administration can be reassured based on the results of this study, and active supportive care may be used during this period. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04116827.

Clinical Characteristics and Prognosis of Metaplastic Breast Cancer Compared with Invasive Ductal Carcinoma: A Propensity-Matched Analysis.

BACKGROUND: Metaplastic breast cancer (MpBC) is an aggressive histologic type of breast cancer. Although MpBC has a poor prognosis and is responsible for a large proportion of breast cancer mortalities, the clinical features of MpBC compared with invasive ductal carcinoma (IDC) are not well known, and the optimal treatment has not been identified. METHODS: We retrospectively reviewed medical records of 155 MpBC patients and 16,251 IDC cases who underwent breast cancer surgery in a single institution between January 1994 and December 2019. The two groups were matched 1:4 by age, tumor size, nodal status, hormonal receptor status, and HER2 status using propensity-score matching (PSM). Finally, 120 MpBC patients were matched with 478 IDC patients. Disease-free survival and overall survival of MpBC and IDC patients both before and after PSM were analyzed by Kaplan-Meier survival, and multivariable Cox regression analysis was performed to identify variables affecting long-term prognosis. RESULTS: The most common subtype of MpBC was triple-negative breast cancer, and nuclear and histologic grades were higher than those of IDC. Pathologic nodal staging of the metaplastic group was significantly lower than that of the ductal group, and more frequent adjuvant chemotherapy was performed in the metaplastic group. Multivariable Cox regression analysis indicated that MpBC was an independent prognostic factor for disease-free survival (HR = 2.240; 95% CI, 1.476-3.399, p = 0.0002) and overall survival (HR = 1.969; 95% CI, 1.147-3.382, p = 0.0140). However, survival analysis revealed no significant difference between MpBC and IDC patients in disease-free survival (HR = 1.465; 95% CI, 0.882-2.432, p = 0.1398) or overall survival (hazard ratio (HR) = 1.542; 95% confidential interval (CI), 0.875-2.718, p = 0.1340) after PSM. CONCLUSION: Although the MpBC histologic type had poor prognostic factors compared with IDC, it can be treated according to the same principles as aggressive IDC.