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.

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.

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.

Early experience of robotic axillary lymph node dissection in patients with node-positive breast cancer.

BACKGROUND: Robotic surgical systems enable surgeons to perform precise movement in the surgical field using high-resolution 3D vision and flexible robotic instruments. We aimed to evaluate the feasibility and safety of performing axillary lymph node dissection using a robotic surgical system in patients with node-positive breast cancer. METHODS: Thirty-two women with breast cancer who underwent robot-assisted nipple-sparing mastectomy (RNSM) and level I/II axillary lymph node dissection were analyzed. Patients were divided into two groups: RNSM with conventional axillary lymph node dissection (CALND) vs. RNSM with robotic axillary lymph node dissection (RALND). Clinicopathological features and surgical outcomes were analyzed. RESULTS: The median age of the patients was 44 (range 20-59) years. Eleven patients underwent RALND. None of the clinicopathologic features differed between the two groups. There were no statistically significant differences in surgical outcomes, except for the final incision size, between the two groups. The proportion of cases with an incision ≤ 40 mm was 63.6% in the RALND group and 36.4% in the CALND group (p = 0.020). CONCLUSION: RALND can be safely performed in RNSM. RNSM with RALND is comparable to RNSM with CALND in terms of early surgical outcomes. The incision size can be reduced when using RALND.

Predicting the Response of Neoadjuvant Chemotherapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer With Axillary Lymph Node Metastasis by Multigene Assay.

PURPOSE: The GenesWell™ breast cancer test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with hormone receptor-positive (HR+) and human epidermal growth factor-2 negative (HER2-) early breast cancer (BC). The ability of this assay to predict the response to neoadjuvant chemotherapy (NACT) has not been established to date. METHODS: Biopsy specimens from HR+/HER2- BC patients with axillary lymph node (LN) metastasis who underwent NACT were analyzed using the BCT score. The modified BCT score was developed and patients classified into high-and low-response groups. A total of 88 patients were available for the BCT score among the 108 eligible patients. The median follow-up duration was 35.9 (7.8-128.5) months. RESULTS: Among them, 61 (65.1%) had cN1 and 53 (60.2%) had cT1 or cT2 disease. The BCT score was low in 25 (28.4%) patients and high in 63 (71.6%). Among the 50 patients with pathologic complete response or partial response, 41 (82.0%) were in the high BCT score group and 9 (18.0%) were in the low BCT score group. Among the 38 patients with stable or progressive disease, 22 (57.9%) were in the high BCT score group and 16 (42.1%) were in the low BCT score group (p = 0.025). Ki-67 before NACT was a significant factor for predicting tumor response (p = 0.006; 3.81 [1.50-10.16]). The BCT score showed a significant response to NACT (p = 0.016; 4.18 [1.34-14.28]). Distant metastasis-free survival was significantly different between the high- and low-response groups (p = 0.004). CONCLUSION: We demonstrated that the BCT score predicts NACT responsiveness in HR+/HER2- BC with LN metastasis and might help determine whether NACT should be performed. Further studies are required to validate these results.

Analysis of robot-assisted nipple-sparing mastectomy using the da Vinci SP system.

BACKGROUND: As patients tend to be diagnosed with breast cancer at an early stage, the demand for better cosmetic outcomes has increased. Several studies revealed that robot-assisted nipple-sparing mastectomy (RNSM) shows favorable outcomes. The aim of the study was to reveal the feasibility of RNSM using the da Vinci single-port (SP) system with a minimal incision, hidden in the arm. METHODS: From 2018 to 2021, 81 cases (70 patients) were retrospectively reviewed. Clinicopathologic characteristics, operative outcomes, and postoperative complications were evaluated. The operative outcomes were analyzed using the Mann-Whitney U test. RESULTS: The median age was 42 years (range, 26-60 years). Bilateral RNSM was performed in 11 (27.2%) patients. The median size of the initial skin incision was 40 mm (range, 20-55 mm). Immediate reconstruction with direct-to-implant was performed in 54 (66.7%) patients and deep inferior epigastric perforator (DIEP) flaps in 15 (18.5%) patients. Postoperative complications of Clavien-Dindo Classification III occurred in six (7.5%) patients. Patients reconstructed with a DIEP flap had large breasts with more severe ptosis, yet grade III complications did not occur. CONCLUSIONS: RNSM using the SP system can be applied for curative and risk-reducing mastectomy, regardless of breast size or ptosis grade.

Ki-67 and breast cancer prognosis: does it matter if Ki-67 level is examined using preoperative biopsy or postoperative specimen?

PURPOSE: This study aimed to identify the association between Ki-67 level and the prognosis of patients with breast cancer, regardless of the timing of Ki-67 testing (using preoperative biopsy vs. postoperative specimen). METHODS: A total of 4177 patients underwent surgery between January 2008 and December 2016. Immunohistochemical Ki-67 levels, using either preoperative (1673) or postoperative (2831) specimens, were divided into four groups using cutoff points of 10%, 15%, and 20%. RESULTS: Groups with higher-Ki-67 levels, in both the pre- and postoperative periods, showed significantly larger tumor size, higher grade, more frequent hormone receptor-negativity and human epidermal growth factor receptor 2 overexpression, and active adjuvant treatments than groups with lower-Ki-67 levels. High-Ki-67 levels were also significantly associated with poor survival, irrespective of the timing of specimen examination. CONCLUSION: Despite the problems associated with Ki-67, Ki-67 level is an important independent prognostic factor, regardless of the timing of Ki-67 testing, i.e., preoperative or postoperative testing.

Level of Combined Estrogen and Progesterone Receptor Expression Determines the Eligibility for Adjuvant Endocrine Therapy in Breast Cancer Patients.

Hormone receptor (HR)-positive breast cancer has a heterogeneous pattern according to the level of receptor expression. Patients whose breast cancers express low levels of estrogen receptor (ER) or progesterone receptor (PgR) may be eligible for adjuvant endocrine therapy, but limited data are available to support this notion. We aimed to determine whether HR expression level is related to prognosis. Tumors from 6042 patients with breast cancer were retrospectively analyzed for combined HR levels of ER and PgR. Low expression was defined as ER 1-10% and PgR 1-20%. Four HR groups were identified by combining ER and PgR expression levels. Patients whose tumors expressed high levels of a single receptor showed the worst survival outcomes, and their risk continuously increased even after the 10-year follow-up. Endocrine therapy had a significant benefit for patients whose tumors expressed high HR levels and a favorable tendency for patients with tumors expressing low HR levels. We established the possible benefit of endocrine therapy for patients whose breast tumors expressed low HR levels. Thus, HR level was a prognostic factor and might be a determinant of extended therapy, especially for patients with high expression of a single receptor.

Highly Selective Xylene Sensor Based on NiO/NiMoO4 Nanocomposite Hierarchical Spheres for Indoor Air Monitoring.

Xylene is a hazardous volatile organic compound, which should be measured precisely for monitoring of indoor air quality. The selective detection of ppm-level xylene using oxide semiconductor chemiresistors, however, remains a challenging issue. In this study, NiO/NiMoO4 nanocomposite hierarchical spheres assembled from nanosheets were prepared by hydrothermal reaction, and the potential of sensors composed of these nanocomposites to selectively detect xylene gas was investigated. The sensors based on the NiO/NiMoO4 nanocomposite hierarchical spheres exhibited high responses (maximum resistance ratio =101.5) to 5 ppm p-xylene with low cross-responses (resistance ratios <30) to 5 ppm toluene, benzene, C2H5OH, CH3COCH3, HCHO, CO, trimethylamine, and NH3. In contrast, a sensor based on pure NiO hierarchical spheres exhibited negligibly low responses to all 9 analyte gases. The gas-sensing mechanism underlying the high selectivity and response to xylene in the NiO/NiMoO4 nanocomposite hierarchical spheres is discussed in relation to the catalytic promotion of the xylene-sensing reaction by synergistic combination between NiO and NiMoO4, gas-accessible hierarchical morphology, and electronic sensitization by Mo addition. Highly selective detection of xylene can pave the road toward a new solution for precise monitoring of indoor air pollution.