Outcomes of sentinel node biopsy according to MRI response in an association with the subtypes in cN1-3 breast cancer after neoadjuvant systemic therapy, multicenter cohort study.

BACKGROUND: This study investigated the feasibility of sentinel lymph node biopsy (SLNB) after neoadjuvant systemic therapy (NAST) in patients with initially high nodal burden. METHODS: In the multicenter retrospective cohort, 388 individuals with cN1-3 breast cancer who underwent NAST and had SLNB followed by completion axillary lymph node dissection were included. In an external validation cohort, 267 patients with HER2+ or triple-negative breast cancer (TNBC) meeting similar inclusion criteria were included. Primary outcome was the false-negative rates (FNRs) of SLNB according to the MRI response and subtypes. We defined complete MRI responders as patients who experienced disappearance of suspicious features in the breast and axilla after NAST. RESULTS: In the multicenter retrospective cohort, 130 (33.5%) of 388 patients were of cN2-3, and 55 (14.2%) of 388 patients showed complete MRI responses. In hormone receptor-positive HER2- (n = 207), complete and non-complete responders had a high FNRs (31.3% [95% CI 8.6-54.0] and 20.9% [95% CI 14.1-27.6], respectively). However, in HER2+ or TNBC (n = 181), the FNR of complete MRI responders was 0% (95% CI 0-0), whereas that of non-complete responders was 33.3% (95% CI 20.8-45.9). When we validated our findings in the external cohort with HER2+ or TNBC (n = 267), of which 34.2% were cN2-3, the FNRs of complete were 7.1% (95% CI 0-16.7). CONCLUSIONS: Our findings suggest that SLNB can be a reliable option for nodal status evaluation in selected patients who have responded well to NAST, especially in HER2+ and TNBC patients who show a complete MRI response.

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

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04993625. Registered on August 6, 2021. Clinical Research Information Service Identifier: KCT0006371. Registered on July 22, 2021.

Psychosocial barriers and facilitators for cascade genetic testing in hereditary breast and ovarian cancer: a scoping review.

Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included 'hereditary breast and ovarian cancer' and 'cascade genetic testing' for studies published from 2012-2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.

The Arthroscopic Biceps Rerouting Technique Shows Better Early Clinical Outcomes within 1 Year Than Partial Repair in Large to Massive Rotator Cuff Tears.

Background and Objectives: The arthroscopic biceps rerouting (BR) technique was introduced as a novel technique for large-to-massive rotator cuff tears (LMRCTs). This method can restore shoulder stability, and its biomechanical effect was verified in a cadaver experiment. Recent reports have shown favorable clinical outcomes. This study aimed to compare the clinical outcomes of partial repair with those of the BR technique in LMRCTs. Materials and Methods: We included 72 patients who had undergone LMRCTs. Arthroscopic partial repair was performed in 31 patients (group I), while repair with the BR technique was performed in 41 patients (group II). Functional and imaging outcomes were evaluated and compared using a visual analog scale for pain, range of motion (ROM), American Shoulder and Elbow Surgeons (ASES) score, Constant score, and Korean Shoulder Score (KSS) before the surgery and at 3, 6, and 12 months after the surgery and at the last follow-up. Tendon integrity was investigated using magnetic resonance in all the patients at 12 months postoperative. Results: The mean follow-up period was 22.11 ± 10.47 months (range, 12-53 months). Forward flexion (p = 0.02) and external rotation at the side (p = 0.04) were significantly higher in group II than in group I on postoperative day (POD) 12 months. For internal rotation, group II showed significant improvement compared to group I on POD 3 months (p = 0.002) and at 6 months postoperative (p = 0.01). On POD 12 months, the ASES (p = 0.047) and KSS (p = 0.048) were better in group II. Significant improvements in pain and clinical scores were observed in both groups at the last follow-up. However, the two groups had no significant differences in pain, clinical scores, or ROM at the last follow-up. Retear of the repaired tendon was observed in nine patients in group I (29.03%) and eight in group II (19.51%, p = 0.35). Conclusions: Partial repair and repair using the BR technique effectively improved clinical and radiologic outcomes. The BR technique revealed early recovery of ROM and better clinical results than partial repair at one year postoperative. This could be a useful method in treating LMRCTs.

A simplified risk scoring system for predicting high-risk groups in gene expression tests for patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and node-positive breast cancer.

Purpose: The gene expression test (GET) was used to predict the response to chemotherapy and the recurrence risk. Several randomized clinical trials have demonstrated that some patients with node-positive disease can achieve favorable survival outcomes even without adjuvant chemotherapy. This study aimed to predict the results of Oncotype DX (Genomic Health) and MammaPrint (Agendia) using traditional clinicopathological factors. Methods: We reviewed the records of 311 patients who underwent GET for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative primary invasive breast cancer with node-positive disease between 2015 and 2022 at Severance Hospital and Gangneung Asan Medical Center. Univariate and multivariate logistic regression analyses assessed the relationships between clinicopathological variables and risk stratification using the GET results. Results: A simple scoring system was created by assigning integer values to each variable. A score of 3 was assigned for histological grade 3, a score of 2 for pathologic T2 or above, and a score of 1 for a lower progesterone receptor (1-20 or Alled score 3-6), HER2 2-positive, and high Ki-67 (>20). In the validation cohort, overall accuracy was 0.798 (95% confidence interval, 0.744-0.844). Conclusion: The high GET risk results can be predicted using traditional clinicopathological factors: tumor size, progesterone receptor, histological grade, HER2, and Ki-67. These results will be useful for treatment decision-making among clinically high-risk patients with HR-positive/HER2-negative and node-positive disease, helping to identify patients to whom the GET assay may not apply.

Lymphovascular invasion is an independent prognostic factor in breast cancer irrespective of axillary node metastasis and molecular subtypes.

Purpose: Lymphovascular invasion (LVI) is a well-known poor prognostic factor for early breast cancer. However, the effect of LVI on breast cancer subtype and node status remains unknown. In this study, we aimed to evaluate the clinical significance of LVI on the recurrence and long-term survival of patients with early breast cancer by comparing groups according to the subtype and node status. Methods: We retrospectively reviewed the medical records of 4554 patients with breast cancer who underwent breast cancer surgery between January 2010 and December 2017. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors related to the DFS and OS according to the nodal status and breast cancer subtype. Results: During a follow-up period of 94 months, the median OS and DFS were 92 and 90 months, respectively. The LVI expression rate was 8.4%. LVI had a negative impact on the DFS and OS, regardless of the lymph node status. LVI was associated with higher recurrence and lower survival in the luminal A, human epidermal growth factor receptor 2-positive, and triple-negative breast cancer subtypes. The Cox proportional hazards model showed that LVI was a significant prognostic factor for both DFS and OS. No correlation has been observed between LVI and the Oncotype Dx results in terms of prognostic value in early breast cancer. Conclusion: LVI is an independent poor prognostic factor in patients with early breast cancer, regardless of the node status and molecular subtype. Therefore, the LVI status should be considered when making treatment decisions for patients with early stage breast cancer; however, further prospective studies are warranted.

Helicobacter pylori Infection Status and Gastric Tumor Incidence According to the Year of Birth.

Background/Aims: : The prevalence of Helicobacter pylori-naive status is increasing. Nonetheless, biennial gastroscopy is recommended for all Koreans aged 40 to 75 years. This study aimed to determine whether gastric cancer screening guidelines could be changed according to H. pylori infection status and year of birth. Methods: : Koreans who underwent serum assays and gastroscopy for gastric cancer screening between 2010 and 2016 were included if screening tests were followed up for ≥3 times. H. pylori infection was confirmed when invasive tests or 13C-urea breath tests were positive. In the case of negative test findings, eradication history, serologically detected atrophy, and intestinal metaplasia/atrophy were checked for past infection. If all were absent, H. pylori-naive status was confirmed. Results: : Two-thousand and two (256 H. pylori-naive, 743 past-infected, and 1,003 infected) Koreans underwent screening tests for 95.5±28.4 months. The mean year of birth in the naive group (1969±7) differed from those of the past-infected (1957±10, p<0.001) and infected (1958±10, p<0.001) groups. H. pylori-naive status was correlated with recent year of birth (r=0.368, p<0.001). No gastric tumors were observed among the naive participants (p=0.007), whereas 23 adenomas, 18 adenocarcinomas, and two neuroendocrine tumors were detected in 1.9% (14/743) of past-infected and 2.5% (25/1,003) of infected participants, including four infected participants with metachronous tumors. Conclusions: : The prevalence of H. pylori-naive status is increasing in young Koreans, and gastric tumors are rare in this population. Hence, biennial gastroscopy could be waived after the confirmation of naive status.

Early experience of direct-to-implant breast reconstruction using acellular dermal matrix after robot-assisted nipple-sparing mastectomy.

BACKGROUND: This study aimed to analyze the novel operative outcomes of breast mound reconstruction followed by robot-assisted mastectomy in retrospective review. METHOD: Patients who underwent nipple-sparing mastectomy with a robotic device (Da Vinci Xi) and immediate prosthetic reconstruction prepectorally via lateral incision from June 2018 to July 2019 were enrolled. Patient characteristics, complications, and satisfaction via BREAST-Q were analyzed. The surgical technique was described in detail. RESULTS: Thirty-nine cases, including 7 bilateral cases (total 46 breasts), underwent robot-assisted nipple-sparing mastectomy followed by immediate prosthetic implant reconstruction prepectorally. The median patient age was 46.63 years (range: 21-63 years). The mean operation time for each prepectoral breast mound reconstruction using the direct-to-implant technique was 126.55 min. Overall satisfaction of robotic use was evaluated as superior to the conventional reconstruction method using BREAST-Q. Major infection was found in seven cases (15.2%), and complete nipple loss was found in three cases (6.6%). Severe complications requiring breast implant removal in the surgical technique occurred in four breasts (8.7%). Two cases were due to the coexistence of infection and skin necrosis; in one case, the skin flap had undergone the congestive phase on postoperative day (POD) 3 and required additional surgery to change the expander. Other complications were resolved by conservative care or minor revision. CONCLUSION: This report is the first concerning robot-assisted NSM followed by prepectoral ADM-wrapped prosthetic reconstruction. In our experience, this procedure seems to be not inferior to other methods. Further prospective research to evaluate oncologic outcomes is warranted.

Distinct Prognosis of Minimal Residual Disease According to Breast Cancer Subtype in Patients with Breast or Nodal Pathologic Complete Response After Neoadjuvant Chemotherapy.

PURPOSE: Few studies have reported on patient prognosis according to residual cancer burden after neoadjuvant chemotherapy (NAC). Herein, we evaluated the survival of patients based on residual disease after NAC to identify subpopulations with distinct prognoses. METHODS: We retrospectively reviewed 728 patients treated with NAC from 2010 to 2017. Patients were divided into four subgroups depending on post-surgical residual disease according to the staging system: pathological complete response (pCR) (ypT0/TisN0), minimal residual disease (MRD) (ypT1mi/T1aN0 or ypT0/Tis ypN0i+/N1mic), node-only pCR (≥ ypT1b ypN0), and breast-only pCR (ypT0/Tis ≥ ypN1a). Clinicopathological characteristics and survival outcomes were analyzed by adjusting for factors affecting survival. RESULTS: Overall, 50.4% (n = 367) of patients achieved pCR, with the MRD group accounting for 16.5% (n = 120). Although age and clinical stage were not different among the study groups, histologic grade, subtypes, chemotherapy response, and local treatment showed differences. Event-free survival (EFS) and overall survival (OS) demonstrated no significant difference between the pCR and MRD groups. In the multivariate analysis, pCR status was the only significant factor in EFS, and no statistical difference was noted between the pCR and MRD groups. However, clinical stage, pCR status, and subtype significantly affected the OS. MRD showed favorable outcomes in terms of both EFS and OS in all subtypes, except for those with triple-negative breast cancer (TNBC). CONCLUSION: Patients with MRD showed outcomes comparable to those of patients who achieved pCR and may be candidates for de-escalation of post-NAC treatment, except for those with a TNBC subtype.

Frozen Sections in Decision-Making Regarding the Axillary Procedures in Breast Conserving Surgery for Intraductal Carcinoma at Preoperative Diagnosis.

BACKGROUND: Axillary evaluation is unnecessary for pure ductal carcinoma in situ (DCIS); however, it is performed because of the risk of upstaging to invasive cancer. We assessed the role of intraoperative frozen section (IOF) biopsy in reducing invasive cancer upstaging and axillary evaluation in preoperative DCIS patients. METHODS: We reviewed patients with preoperative DCIS who underwent breast-conserving surgery (BCS) with IOF biopsy. Positive IOF biopsy findings were defined as the presence of invasive or micro-invasive cancer. The IOF biopsy and permanent pathology findings were compared. RESULTS: Seventy-eight patients underwent BCS with IOF biopsy. Six patients showed positive IOF biopsy findings; five of these patients showed concordant permanent pathology findings. Sentinel lymph node biopsy (SLNB) was positive in one patient. Thirteen patients with invasive breast cancer were missed by IOF biopsy; they underwent SLNB during the second surgery. None of them had metastatic lymph nodes. The sensitivity and specificity of IOF biopsy were 27.7% and 98.3%, respectively, with 82.1% accuracy. None of the other factors showed statistically significant relationships with the permanent pathology findings, except for the IOF biopsy findings. CONCLUSION: IOF evaluation can aid in detecting the invasiveness of tumors in patients with preoperative DCIS.

Oncologic Outcomes in Nipple-sparing Mastectomy with Immediate Reconstruction and Total Mastectomy with Immediate Reconstruction in Women with Breast Cancer: A Machine-Learning Analysis.

BACKGROUND: This study used a single-institution cohort, the Severance dataset, validated the results by using the surveillance, epidemiology, and end results (SEER) database, adjusted with propensity-score matching (PSM), and analyzed by using a machine learning method. To determine whether the 5-year, disease-free survival (DFS) and overall survival (OS) of patients undergoing nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) are not inferior to those of women treated with total mastectomy/skin-sparing mastectomy (TM/SSM). METHODS: The Severance dataset enrolled 611 patients with early, invasive breast cancer from 2010 to 2017. The SEER dataset contained data for 485,245 patients undergoing TM and 14,770 patients undergoing NSM between 2000 and 2018. All patients underwent mastectomy and IBR. Intraoperative, frozen-section biopsy for the retro-areolar tissue was performed in the NSM group. The SEER dataset was extracted by using operation types, including TM/SSM and NSM. The primary outcome was DFS for the Severance dataset and OS for the SEER dataset. PSM analysis was applied. Survival outcomes were analyzed by using the Kaplan-Meier method and Cox proportional hazard (Cox PH) regression model. We implemented XGBSE to predict mortality with high accuracy and evaluated model prediction performance using a concordance index. The final model inspected the impact of relevant predictors on the model output using shapley additive explanation (SHAP) values. RESULTS: In the Severance dataset, 151 patients underwent NSM with IBR and 460 patients underwent TM/SSM with IBR. No significant differences were found between the groups. In multivariate analysis, NSM was not associated with reduced oncologic outcomes. The same results were observed in PSM analysis. In the SEER dataset, according to the SHAP values, the individual feature contribution suggested that AJCC stage ranks first. Analyses from the two datasets confirmed no impact on survival outcomes from the two surgical methods. CONCLUSIONS: NSM with IBR is a safe and feasible procedure in terms of oncologic outcomes. Analysis using machine learning methods can be successfully applied to identify significant risk factors for oncologic outcomes.

Twice-daily intake of bismuth-based quadruple therapy for first-line Helicobacter pylori eradication: A retrospective study on 10-day, 14-day, and half-dose antibiotic therapy.

BACKGROUND/AIMS: In areas with >15% clarithromycin resistance, bismuth-based quadruple therapy is recommended for first-line Helicobacter pylori eradication. This study aimed to determine the efficacy of the twice-daily intake of bismuth-based quadruple therapy among 10-day, 14-day, and half-dose antibiotic regimens. METHODS: From May 2021 to March 2023, H. pylori-infected Korean adults were administered tetracycline (1 g), metronidazole (750 mg), bismuth potassium citrate (300 mg), and lansoprazole (30 mg) twice daily, after breakfast and dinner, for 10 days. The regimen was administered for 14 days if the body weight was ≥70 kg or if the patient had reinfection. Half doses of antibiotics were administered for 14 days if there was a risk of drug interactions or if the patient was aged ≥75 years. The 13 C-urea breath test was performed after 6 weeks. RESULTS: Among the 1258 infected Koreans, 85.1% (412/484) in the 10-day, 84.3% (498/591) in the 14-day, and 86.3% (158/183) in the half-dose antibiotic groups followed the instructions. In the per-protocol (PP) analysis, eradication rates were higher in the 10-day (90.5%, p = 0.019) and 14-day (90.2%, p = 0.023) groups than in the half-dose group (83.5%). In the intention-to-treat (ITT) analysis, eradication rates were higher in the 10-day group (80.6%) than in the half-dose group (73.2%, p = 0.039). In the half-dose group, the eradication rate was lower in patients aged ≥75 years (PP: 74.6%, ITT: 66.2%) than in those with a risk of drug interactions (PP: 89.7% [p = 0.017], ITT: 82.4% [p = 0.019]). CONCLUSIONS: Twice-daily intake of bismuth-based quadruple therapy for 10-14 days showed an eradication rate of >90% in the PP analysis. A 10-day regimen could be administered to eradication-naive patients with a body weight below 70 kg. A half-dose antibiotic regimen might be recommended to patients with a risk of drug interactions but not to those aged ≥75 years simply due to old age.

Controversies and strengths of robot-assisted mastectomy.

Nipple-sparing mastectomy (NSM) is used to improve cosmetic outcomes while maintaining oncological safety in patients with early breast cancer; however, NSM requires a higher level of skill and workload than mastectomy and is associated with long, visible scars. Robotic surgical systems reduce surgeon workload and facilitate precise surgery. Considering the increasing support of robot-assisted NSM (RNSM), this paper aims to discuss the current controversies based on the research findings reported thus far. There are four concerns regarding RNSM; increased cost, oncological outcomes, the level of experience and skill, and standardization. It should be noted that RNSM is not a surgery performed on all patients but rather a procedure performed on selected patients who meet specific indications. A large-scale randomized clinical trial comparing robotic and conventional NSM has recently begun in Korea; therefore, it is necessary to wait for these results for more insight into oncological outcomes. Although the level of experience and skill required for robotic mastectomy may not be easily achieved by all surgeons, the learning curve for RNSM appears manageable and can be overcome with appropriate training and practice. Training programs and standardization efforts will help improve the overall quality of RNSM. There are some advantages to RNSM. The robotic system provides improved precision and accuracy, helping remove breast tissue more effectively. RNSM has advantages such as smaller scars, less blood loss, and a lower rate of surgical complications. Patients who undergo RNSM report better quality of life.

Mastectomy with Reconstruction Including Robotic Endoscopic Surgery (MARRES): a prospective cohort study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) and Korean Breast Cancer Study Group (KBCSG).

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) has emerged as a new treatment option for breast cancer and risk-reducing mastectomy (RRM) for women who have a high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that it should only be performed by specialized surgeons, and data on oncologic outcomes and patient-reported outcomes (PROs) are limited. Recently, the United States Food and Drug Administration and several surgeons warned that robotic breast surgery should be performed only by specialized surgeons and recommended that the benefits, risks, and alternatives of all available treatment options be discussed with patients so they can make informed treatment decisions. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and teach this state-of-the-art procedure. We have designed a multicenter prospective cohort study entitled Mastectomy with Reconstruction Including Robot Endoscopic Surgery (MARRES) to report surgical, PRO, and oncologic outcomes. METHODS: MARRES is a multi-institution cohort study prospectively collecting data from patients undergoing mastectomy and reconstruction. The patient inclusion criteria are adult women older than 19 with breast cancer or a high risk of breast cancer (patients with BRCA1/2, TP53, PALB2 mutations, etc.), who have scheduled therapeutic or RRM and want immediate reconstruction. Surgical outcomes, including pre- and postoperative photos, oncologic outcomes, cost-effectiveness, and PRO, are collected. The primary endpoints are postoperative complication rates within 30 postoperative days and the Clavien-Dindo grade of postoperative complications within 180 postoperative days. The secondary endpoints are 5-year postoperative recurrence-free survival and cancer incidence rate (for those who underwent RRM), patient satisfaction with reconstruction expectations preoperative (baseline) and results within 6 to 12 postoperative months, surgeon satisfaction with postoperative results in 6 postoperative months, and cost-effectiveness of the definitive surgery. Patient recruitment will be completed in April 2025, and the target number of enrolled patients is 2000. DISCUSSION: This study will provide evidence about the surgical outcomes, oncologic outcomes, and patient satisfaction with RNSM and endoscopic nipple-sparing mastectomy (NSM), compared with conventional NSM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04585074. Registered April 8, 2020.

Copy number aberrations in circulating tumor DNA enables prognosis prediction and molecular characterization of breast cancer.

BACKGROUND: Low-pass whole-genome sequencing (LP-WGS)-based circulating tumor DNA (ctDNA) analysis is a versatile tool for somatic copy number aberration (CNA) detection, and this study aims to explore its clinical implication in breast cancer. METHODS: We analyzed LP-WGS ctDNA data from 207 metastatic breast cancer (MBC) patients to explore prognostic value of ctDNA CNA burden and validated it in 465 stage II-III triple-negative breast cancer (TNBC) patients who received neoadjuvant chemotherapy in phase III PEARLY trial (NCT02441933). The clinical implication of locus level LP-WGS ctDNA profiling was further evaluated. RESULTS: We found that a high baseline ctDNA CNA burden predicts poor overall survival and progression-free survival of MBC patients. The post hoc analysis of the PEARLY trial showed that a high baseline ctDNA CNA burden predicted poor disease-free survival independent from pathologic complete response (pCR), validating its robust prognostic significance. The 24-month disease-free survival rate was 96.9% and 55.9% in [pCR(+) and low I-score] and [non-pCR and high I-score] patients, respectively. The locus-level ctDNA CNA profile classified MBC patients into 5 molecular clusters and revealed targetable oncogenic CNAs. LP-WGS ctDNA and in vitro analysis identified the BCL6 amplification as a resistance factor for CDK4/6 inhibitors. We estimated ctDNA-based homologous recombination deficiency status of patients by shallowHRD algorithm, which was highest in the TNBC and correlated with platinum-based chemotherapy response. CONCLUSIONS: These results demonstrate LP-WGS ctDNA CNA analysis as an essential tool for prognosis prediction and molecular profiling. Particularly, ctDNA CNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients.

Changes in Automated Mammographic Breast Density Can Predict Pathological Response After Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: Mammographic density is an independent risk factor for breast cancer that can change after neoadjuvant chemotherapy (NCT). This study aimed to evaluate percent changes in volumetric breast density (ΔVbd%) before and after NCT measured automatically and determine its value as a predictive marker of pathological response to NCT. MATERIALS AND METHODS: A total of 357 patients with breast cancer treated between January 2014 and December 2016 were included. An automated volumetric breast density (Vbd) measurement method was used to calculate Vbd on mammography before and after NCT. Patients were divided into three groups according to ΔVbd%, calculated as follows: Vbd (post-NCT - pre-NCT)/pre-NCT Vbd × 100 (%). The stable, decreased, and increased groups were defined as -20% ≤ ΔVbd% ≤ 20%, ΔVbd% < -20%, and ΔVbd% > 20%, respectively. Pathological complete response (pCR) was considered to be achieved after NCT if there was no evidence of invasive carcinoma in the breast or metastatic tumors in the axillary and regional lymph nodes on surgical pathology. The association between ΔVbd% grouping and pCR was analyzed using univariable and multivariable logistic regression analyses. RESULTS: The interval between the pre-NCT and post-NCT mammograms ranged from 79 to 250 days (median, 170 days). In the multivariable analysis, ΔVbd% grouping (odds ratio for pCR of 0.420 [95% confidence interval, 0.195-0.905; P = 0.027] for the decreased group compared with the stable group), N stage at diagnosis, histologic grade, and breast cancer subtype were significantly associated with pCR. This tendency was more evident in the luminal B-like and triple-negative subtypes. CONCLUSION: ΔVbd% was associated with pCR in breast cancer after NCT, with the decreased group showing a lower rate of pCR than the stable group. Automated measurement of ΔVbd% may help predict the NCT response and prognosis in breast cancer.

Efficacy of Limited Dose Modifications for Palbociclib-Related Grade 3 Neutropenia in Hormone Receptor-Positive Metastatic Breast Cancer.

PURPOSE: Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)-positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. MATERIALS AND METHODS: Patients with HR-positive, human epidermal growth factor receptor 2-negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. RESULTS: During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. CONCLUSION: Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

Comparison of Clinical Outcomes of Platelet-Rich Plasma for Epicondylitis, Elbow: Simultaneous Lateral and Medial Versus Lateral Versus Medial.

OBJECTIVE: Lateral and medial epicondylitis are relatively common diseases, but they do not improve quickly and are known to reduce patients' quality of life. Much research has been done on Platelet-Rich Plasma (PRP) as a treatment for lateral epicondylitis, but research on medial epicondylitis is lacking. The purpose of this study is to compare: (i) the pain intensity; and (ii) the functional outcome between the simultaneous treatment of medial and lateral epicondylitis and the treatment of only lateral or medial epicondylitis using PRP. METHODS: In this retrospective study, 209 patients treated with PRP on epicondylitis between March 2018 and December 2021 were enrolled. Simultaneous treatment was underwent 68 patients (group I). Seventy patients were treated for lateral epicondylitis (group II). The remaining 71 patients were treated for medial epicondylitis (group III). The visual analogue scale for pain (VAS) and the Mayo elbow performance score (MEPS) were evaluated for clinical outcomes at the initial visit and 6 months after injection. RESULTS: VAS for pain and MEPS showed significant improvement in all three groups compared to before treatment. There was no significant difference between three groups on -ΔVAS (P > 0.05). However, in case of ΔMEPS, group III showed significantly lower compared to groups II and III (P < 0.05). No patients showed worsening of symptoms or complications during the treatment. CONCLUSION: PRP injection for the patient with elbow medial and lateral epicondylitis can be treated effectively simultaneously in terms of pain. From a functional point of view, the effect of simultaneous treatment may be lessened than in the case of only lateral and medial treatment.

On-treatment derived neutrophil-to-lymphocyte ratio and survival with palbociclib and endocrine treatment: analysis of a multicenter retrospective cohort and the PALOMA-2/3 study with immune correlates.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have been established as a standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC); however, predictive biomarkers with translational relevance have not yet been elucidated. METHODS: Data from postmenopausal women who received the CDK4/6 inhibitor palbociclib and letrozole for HR-positive, HER2-negative ABC from tertiary referral centers were analyzed (N = 221; exploratory cohort). Pre- and on-treatment neutrophil-to-lymphocyte ratio (NLR) and derived NLR (dNLR; neutrophil/[leukocyte-neutrophil]) were correlated with survival outcomes. Data from the PALOMA-2 (NCT01740427) and PALOMA-3 studies (NCT01942135) involving patients treated with endocrine treatment with or without palbociclib were also analyzed (validation cohort). Prospectively enrolled patients (N = 20) were subjected to immunophenotyping with circulating immune cells to explore the biological implications of immune cell dynamics. RESULTS: In the exploratory cohort, palbociclib administration significantly reduced leukocyte, neutrophil, and lymphocyte counts on day 1 of cycle 2. Although the baseline dNLR was not significantly associated with progression-free survival (PFS), higher on-treatment dNLRs were associated with worse PFS (hazard ratio = 3.337, P < 0.001). In the PALOMA-2 validation cohort, higher on-treatment dNLRs were associated with inferior PFS in patients treated with palbociclib and letrozole (hazard ratio = 1.498, P = 0.009), and reduction in the dNLR after treatment was predictive of a survival benefit (hazard ratio = 1.555, P = 0.026). On-treatment dNLRs were also predictive of PFS following palbociclib and fulvestrant treatment in the PALOMA-3 validation cohort. Using flow cytometry analysis, we found that the CDK4/6 inhibitor prevented T cell exhaustion and diminished myeloid-derived suppressor cell frequency. CONCLUSIONS: On-treatment dNLR significantly predicted PFS in patients with HR-positive, HER2-negative ABC receiving palbociclib and endocrine treatment. Additionally, we observed putative systemic immune responses elicited by palbociclib, suggesting immunologic changes upon CDK4/6 inhibitor treatment.