Selective omission of sentinel lymph node biopsy in mastectomy for ductal carcinoma in situ: identifying eligible candidates.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for patients with ductal carcinoma in situ (DCIS) undergoing mastectomy, given the concerns regarding upstaging and technical difficulties of post-mastectomy SLNB. However, this may lead to potential overtreatment, considering favorable prognosis and de-escalation trends in DCIS. Data regarding upstaging and axillary lymph node metastasis among these patients remain limited. METHODS: We retrospectively reviewed patients with DCIS who underwent mastectomy with SLNB or axillary lymph node dissection at Gangnam Severance Hospital between January 2010 and December 2021. To explore the feasibility of omitting SLNB, we assessed the rates of DCIS upgraded to invasive carcinoma and axillary lymph node metastasis. Binary Cox regression analysis was performed to identify clinicopathologic factors associated with upstaging and axillary lymph node metastasis. RESULTS: Among 385 patients, 164 (42.6%) experienced an invasive carcinoma upgrade: microinvasion, pT1, and pT2 were confirmed in 53 (13.8%), 97 (25.2%), and 14 (3.6%) patients, respectively. Seventeen (4.4%) patients had axillary lymph node metastasis. Multivariable analysis identified age ≤ 50 years (adjusted odds ratio [OR], 12.73; 95% confidence interval [CI], 1.18-137.51; p = 0.036) and suspicious axillary lymph nodes on radiologic evaluation (adjusted OR, 9.31; 95% CI, 2.06-41.99; p = 0.004) as independent factors associated with axillary lymph node metastasis. Among patients aged > 50 years and/or no suspicious axillary lymph nodes, only 1.7-2.3%) experienced axillary lymph node metastasis. CONCLUSIONS: Although underestimation of the invasive component was relatively high among patients with DCIS undergoing mastectomy, axillary lymph node metastasis was rare. Our findings suggest that omitting SLNB may be feasible for patients over 50 and/or without suspicious axillary lymph nodes on radiologic evaluation.

Tumor-Infiltrating Lymphocyte Level Consistently Correlates with Lower Stiffness Measured by Shear-Wave Elastography: Subtype-Specific Analysis of Its Implication in Breast Cancer.

Background: We aimed to elucidate the clinical significance of tumor stiffness across breast cancer subtypes and establish its correlation with the tumor-infiltrating lymphocyte (TIL) levels using shear-wave elastography (SWE). Methods: SWE was used to measure tumor stiffness in breast cancer patients from January 2016 to August 2020. The association of tumor stiffness and clinicopathologic parameters, including the TIL levels, was analyzed in three breast cancer subtypes. Results: A total of 803 patients were evaluated. Maximal elasticity (Emax) showed a consistent positive association with an invasive size and the pT stage in all cases, while it negatively correlated with the TIL level. A subgroup-specific analysis revealed that the already known parameters for high stiffness (lymphovascular invasion, lymph node metastasis, Ki67 levels) were significant only in hormone receptor-positive and HER2-negative breast cancer (HR + HER2-BC). In the multivariate logistic regression, an invasive size and low TIL levels were significantly associated with Emax in HR + HER2-BC and HER2 + BC. In triple-negative breast cancer, only TIL levels were significantly associated with low Emax. Linear regression confirmed a consistent negative correlation between TIL and Emax in all subtypes. Conclusions: Breast cancer stiffness presents varying clinical implications dependent on the tumor subtype. Elevated stiffness indicates a more aggressive tumor biology in HR + HER2-BC, but is less significant in other subtypes. High TIL levels consistently correlate with lower tumor stiffness across all subtypes.

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.

Feasibility of Intraoperative Radiotherapy Tumor Bed Boost in Patients with Breast Cancer after Neoadjuvant Chemotherapy.

PURPOSE: This study aimed to assess the feasibility and safety of administering intraoperative radiotherapy (IORT) as a boost during breast-conserving surgery (BCS) following neoadjuvant chemotherapy for patients at high risk of breast cancer recurrence. MATERIALS AND METHODS: Patients who underwent neoadjuvant chemotherapy received a single 20-Gy dose of IORT during BCS, followed by external beam radiotherapy 4-6 weeks after surgery. RESULTS: The median follow-up duration was 31.0 months (range, 18.0-59.0 months). Initial tumor sizes had a median of 2.6 cm (range: 0.8-5.3 cm), reducing to 0.3 cm (range: 0-4.0 cm) after neoadjuvant chemotherapy. The most common neoadjuvant chemotherapy regimen was doxorubicin and cyclophosphamide, followed by paclitaxel (n=42, 73.7%). Among 57 patients who received neoadjuvant chemotherapy before BCS and IORT, 2 patients (3.5%) required secondary surgery to achieve negative resection margins due to initially positive margins. Regional lymph node irradiation was performed in 37 (64.9%) patients. There was no grade 3 or higher adverse events, with 4 patients (7.0%) experiencing grade 2 acute radiation dermatitis and 3 (5.3%) having less than grade 2 breast edema. Binary correlation analysis did not reveal statistically significant associations between applicator size or radiation therapy modality and the risk of treatment-related toxicity. Furthermore, chi-square analysis showed that the grade of treatment-related toxicity was not associated with the fractionated regimen (p=0.375). CONCLUSION: Most patients successfully received IORT as a tumor bed boost after neoadjuvant chemotherapy. Thus, IORT may be a safe and feasible option for patients with advanced-stage breast cancer receiving neoadjuvant chemotherapy.

Predictive Markers of Treatment Response to Neoadjuvant Systemic Therapy with Dual HER2-Blockade.

In patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, achievement of pathologic complete response (pCR) is a known prognostic indicator after neoadjuvant systemic therapy (NAST). We investigated the clinicopathological factors associated with pCR in patients with HER2-positive breast cancer treated with dual HER2-blockade. In this retrospective study, 348 patients with HER2-positive breast cancer who received NAST with docetaxel and carboplatin, combined with trastuzumab and pertuzumab (TCHP), were included. Of the 348 patients with HER2 protein expression data, 278 (79.9%) had HER2 immunochemistry (IHC) 3+. Data on tumor-infiltrating lymphocyte (TIL) levels were available for 305 patients, showing a median TIL level of 20% (IQR 5-50), among which 121 (39.7%) had high TIL levels (≥30%). Estrogen receptor (ER) status (77.9% in ER-negative vs. 47.5% in ER-positive; p < 0.001), HER2 protein expression (71.6% in IHC 3+ vs. 34.3% in IHC 2+; p < 0.001), and TIL levels (71.9% in high vs. 57.6% in low; p = 0.011) were significantly associated with the pCR rate. In addition, we observed a significant link between numerical TIL levels (per 10% increment) and the pCR rate. After adjusting other clinicopathologic factors, ER status (low expression [defined as 1-9% expression] or negative), HER2 IHC 3+ and numerical TIL levels (per 10% increment), and high TIL levels (≥30%) were found to be independent predictors of pCR. Notably, in ER-negative breast cancer, the treatment response was excellent, irrespective of HER2 expression and TIL levels. Conversely, in ER-positive cases, low ER expression, HER2 IHC 3+, and numerical TIL levels or high TIL levels emerged as independent predictors of pCR. Our results suggest that ER expression, HER2 protein expression, and TIL levels serve as valuable predictors of the treatment response to neoadjuvant TCHP.

Elasticity Values as a Predictive Modality for Response to Neoadjuvant Chemotherapy in Breast Cancer.

Shear-wave elastography (SWE) is an effective tool in discriminating malignant lesions of breast and axillary lymph node metastasis in patients with breast cancer. However, the association between the baseline elasticity value of breast cancer and the treatment response of neoadjuvant chemotherapy is yet to be elucidated. Baseline SWE measured mean stiffness (E-mean) and maximum stiffness (E-max) in 830 patients who underwent neoadjuvant chemotherapy and surgery from January 2012 to December 2022. Association of elasticity values with breast pCR (defined as ypTis/T0), pCR (defined as ypTis/T0, N0), and tumor-infiltrating lymphocytes (TILs) was analyzed. Of 830 patients, 356 (42.9%) achieved breast pCR, and 324 (39.0%) achieved pCR. The patients with low elasticity values had higher breast pCR and pCR rates than those with high elasticity values. A low E-mean (adjusted odds ratio (OR): 0.620; 95% confidence interval (CI): 0.437 to 0.878; p = 0.007) and low E-max (adjusted OR: 0.701; 95% CI: 0.494 to 0.996; p = 0.047) were independent predictive factors for breast pCR. Low elasticity values were significantly correlated with high TILs. Pretreatment elasticity values measured using SWE were significantly associated with treatment response and inversely correlated with TILs, particularly in HR+HER2- breast cancer and TNBC.

BRCA1 mutation promotes sprouting angiogenesis in inflammatory cancer-associated fibroblast of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with inferior outcomes owing to its low treatment response and high invasiveness. Based on abundant cancer-associated fibroblasts (CAFs) and frequent mutation of breast cancer-associated 1 (BRCA1) in TNBC, the characteristics of CAFs in TNBC patients with BRCA1 mutation compared to wild-type were investigated using single-cell analysis. Intriguingly, we observed that characteristics of inflammatory CAFs (iCAFs) were enriched in patients with BRCA1 mutation compared to the wild-type. iCAFs in patients with BRCA1 mutation exhibited outgoing signals to endothelial cells (ECs) clusters, including chemokine (C-X-C motif) ligand (CXCL) and vascular endothelial growth factor (VEGF). During CXCL signaling, the atypical chemokine receptor 1 (ACKR1) mainly interacts with CXCL family members in tumor endothelial cells (TECs). ACKR1-high TECs also showed high expression levels of angiogenesis-related genes, such as ANGPT2, MMP1, and SELE, which might lead to EC migration. Furthermore, iCAFs showed VEGF signals for FLT1 and KDR in TECs, which showed high co-expression with tip cell marker genes, including ZEB1 and MAFF, involved in sprouting angiogenesis. Moreover, BRCA1 mutation patients with relatively abundant iCAFs and tip cell gene expression exhibited a limited response to neoadjuvant chemotherapy, including cisplatin and bevacizumab. Importantly, our study observed the intricate link between iCAFs-mediated angiogenesis and chemoresistance in TNBC with BRCA1 mutation.

Breast density reduction as a predictor for prognosis in premenopausal women with estrogen receptor-positive breast cancer: an exploratory analysis of the updated ASTRRA study.

BACKGROUND: While the relationship between mammographic breast density reduction (MDR) and endocrine therapy efficacy has been reported in estrogen receptor (ER)-positive breast cancer, it is still unclear in premenopausal women, especially in the case of adding ovarian function suppression (OFS) to antihormone therapy. The authors investigated the impact of MDR on prognosis stratified by treatment based on the updated results of the ASTRRA trial. MATERIALS AND METHODS: The ASTRRA trial, a randomized phase III study, showed that adding OFS to tamoxifen (TAM) improved survival in premenopausal women with estrogen receptor-positive breast cancer after chemotherapy. The authors updated survival outcomes and assessed mammography before treatment and the annual follow-up mammography for up to 5 years after treatment initiation. Mammographic density (MD) was classified into four categories based on the Breast Imaging-Reporting and Data System. MDR-positivity was defined as a downgrade in MD grade on follow-up mammography up to 2 years after randomization, with pretreatment MD grade as a reference. RESULTS: The authors evaluated MDR in 944 of the 1282 patients from the trial, and 813 (86.2%) had grade III or IV MD. There was no difference in the MDR-positivity rate between the two treatment groups [TAM-only group (106/476 (22.3%)) vs. TAM+OFS group (89/468 (19.0%)); P =0.217). MDR-positivity was significantly associated with better disease-free survival (DFS) in the TAM+OFS group (estimated 8-year DFS: 93.1% in MDR-positive vs. 82.0% in MDR-negative patients; HR: 0.37; 95% CI: 0.16-0.85; P =0.019), but not in the TAM-only group ( Pinteraction =0.039). MDR-positive patients who received TAM+OFS had a favorable DFS compared to MDR-negative patients who received only TAM (HR: 0.30; 95% CI: 0.13-0.70; P =0.005). CONCLUSION: Although the proportion of MDR-positive patients was comparable between both treatment groups, MDR-positivity was independently associated with favorable outcomes only in the TAM+OFS group.

YAP1 Expression in HR+HER2- Breast Cancer: 21-Gene Recurrence Score Analysis and Public Dataset Validation.

BACKGROUND: YAP1, an oncogene in numerous cancers, is a downstream transcription factor of the Hippo pathway. This study focuses on its relationship with the Oncotype Dx (ODX) test risk score (RS) in patients with hormone-receptor-positive, HER2-negative (HR+HER2-) breast cancer. METHODS: We retrospectively analyzed 401 HR+HER2- breast cancer patients from Gangnam Severance Hospital who underwent ODX tests (May 2014-April 2020). YAP1 nuclear localization was evaluated via immunohistochemical staining and its clinical correlation with clinicopathological parameters, including RS, was analyzed. Public datasets TCGA-BRCA and METABRIC validated clinical outcomes. RESULTS: YAP1 expression negatively correlated with ODX RS (OR 0.373, p = 0.002). Elevated YAP1 mRNA levels corresponded to better clinical outcomes, specifically in ER-positive patients, with significant results in METABRIC and TCGA-BRCA datasets (p < 0.0001 OS in METABRIC, p = 0.00085 RFS in METABRIC, p = 0.040 DFS in TCGA-BRCA). In subsets with varying ESR1 mRNA expression and pronounced YAP1 expression, superior survival outcomes were consistently observed. CONCLUSION: YAP1 may be a valuable prognostic marker and potential therapeutic target in HR+HER2- breast cancer patients.

Prognostic impact of radiotherapy-induced-lymphopenia in patients treated with breast-conservative surgery.

We investigated a prognostic impact of radiotherapy-induced lymphopenia (RIL) in breast cancer patients treated with breast-conservative surgery (BCS). We included 531 breast cancer patients who were treated with BCS and adjuvant radiotherapy. None of these received (neo)adjuvant chemotherapy. Pre- and post- absolute lymphocyte counts (ALC) were reviewed before and after radiotherapy. The primary endpoint was to evaluate recurrence-free survival (RFS) according to the pre-to-post ALC ratio. Binary logistic regression model was used to identify risk factors for RIL. Either continuous or categorical (> 2.4) pre-to-post ALC ratio was associated with RFS. In 531 patients receiving whole breast irradiation (WBI) and regional nodal irradiation (RNI), RFS was significantly reduced in the patients with high pre-to-post ALC ration (> 2.4). In multivariable analysis, low pre-to-post post ALC ratio was significantly related to decreased RFS in the multivariable analysis (HR 2.293, 95% CIs 1.110-4.735, P = 0.025). In 452 patients treated with WBI alone, high pre-to-post ALC ratio was still significantly associated with decreased RFS in the multivariable analysis (HR 2.708, 95% CIs 1.016-7.218, P = 0.046). In binary logistic regression analysis, RNI was only significant risk factor for clinically meaningful RIL. Our findings show that a markedly decrease in ALC during radiotherapy has a negative prognostic impact.

Ki-67, 21-Gene Recurrence Score, Endocrine Resistance, and Survival in Patients With Breast Cancer.

Importance: Both high 21-gene recurrence score (RS) and high Ki-67 level are poor prognostic factors in patients with estrogen receptor (ER)-positive ERBB2-negative (ER+/ERBB-) breast cancer; however, a discrepancy between the 2 has been noted. Survival differences according to these 2 biomarkers are not well known. Objective: To assess the associations between RS and Ki-67 expression and between Ki-67 expression and recurrence-free survival in patients with ER+/ERBB- breast cancer with low RS. Design, Setting, and Participants: This cohort study included women treated for ER+/ERBB2- breast cancer who underwent the 21-gene RS test from March 2010 to December 2020 in 2 hospitals in Korea. Exposures: Recurrence score and Ki-67 level. Main Outcomes and Measures: A Cox proportional hazards regression model was used to examine the association of Ki-67 with recurrence-free survival (RFS), while a binary logistic regression model was used to examine the association between Ki-67 and secondary endocrine resistance. High Ki-67 expression was defined as 20% or greater, and low genomic risk as an RS of 25 or less. Secondary endocrine resistance was defined as breast cancer recurrence that occurred after at least 2 years of endocrine therapy and during or within the first year after completing 5 years of adjuvant endocrine therapy. Results: A total of 2295 female patients were included (mean [SD] age, 49.8 [9.3] years), of whom 1948 (84.9%) were in the low genomic risk group and 1425 (62.1%) had low Ki-67 level. The median follow-up period was 40 months (range, 0-140 months). The RS and Ki-67 level had a moderate correlation (R = 0.455; P < .001). Of the patients with low Ki-67 level, 1341 (94.1%) had low RS, whereas 607 of 870 patients with high Ki-67 level (69.8%) had low RS. In patients with low RS, the RFS differed significantly according to Ki-67 level (low Ki-67, 98.5% vs high Ki-67, 96.5%; P = .002). Among the 1807 patients with low genomic risk who did not receive chemotherapy, high Ki-67 level was independently associated with recurrence (hazard ratio, 2.51; 95% CI, 1.27-4.96; P = .008). Recurrence after 3 years differed significantly according to Ki-67 level (low Ki-67, 98.7% vs high Ki-67, 95.7%; P = .003), whereas recurrence within 3 years did not differ (low Ki-67, 99.3% vs high Ki-67, 99.3%; P = .90). In addition, Ki-67 was associated with secondary endocrine resistance in patients with low RS who did not receive chemotherapy (odds ratio, 2.49; 95% CI, 1.13-5.50; P = .02). Conclusions and Relevance: In this cohort study of patients with ER+/ERBB2- breast cancer, a moderate correlation was observed between Ki-67 and RS, and high Ki-67 level in patients with low genomic risk was associated with increased risk of secondary endocrine resistance.

Optimal treatment strategy for hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer patients with 1-2 suspicious axillary lymph node metastases on breast magnetic resonance imaging: upfront surgery vs. neoadjuvant chemotherapy.

Background: It is unclear whether upfront surgery or neoadjuvant chemotherapy is appropriate for first treatment in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients with 1-2 suspicious axillary lymph node (ALN) metastases on preoperative breast magnetic resonance imaging (MRI). Method: We identified 282 patients with HR+HER2- breast cancer and 1-2 suspicious ALN metastases on baseline breast MRI (147 received upfront surgery; 135 received neoadjuvant chemotherapy). We evaluated the predictive clinicopathological factors for pN2-3 in the adjuvant setting and axillary pathologic complete response (pCR) in the neoadjuvant setting. Results: Lymphovascular invasion (LVI)-positive and clinical tumors >3 cm were significantly associated with pN2-3 in patients who received upfront surgery. The pN2-3 rate was 9.3% in patients with a clinical tumor ≤ 3 cm and LVI-negative versus 34.7% in the others (p < 0.001). The pN2-3 rate in patients with a clinical tumor ≤ 3 cm and LVI-negative and in the others were 9.3% versus 34.7% in all patients (p < 0.001), 10.7% versus 40.0% (p = 0.033) in patients aged < 50 years, and 8.5% versus 31.0% in patients aged ≥ 50 years (p < 0.001), respectively. In the neoadjuvant setting, patients with tumor-infiltrating lymphocytes (TILs) ≥ 20% had a higher axillary pCR than those with TILs < 20% (46.7% vs. 15.3%, p < 0.001). A similar significant finding was also observed in patients < 50 years. Conclusions: Upfront surgery may be preferable for patients aged ≥ 50 years with a clinical tumor < 3 cm and LVI-negative, while neoadjuvant chemotherapy may be preferable for those aged < 50 years with TILs ≥ 20%.

Investigation of Factors Affecting Adherence to Adjuvant Hormone Therapy in Early-Stage Breast Cancer Patients: A Comprehensive Systematic Review.

PURPOSE: Adherence and persistence to adjuvant hormone therapy (AHT) are seldom maintained among early-stage hormone receptor-positive breast cancer (BC) survivors, despite the significant clinical benefits of long-term AHT. As the factors influencing adherence to AHT remain unclear, this study aimed to comprehensively identify such factors and classify them into specific dimensions. METHODS: PubMed, Cochrane Library, Embase, PsycINFO, and CINAHL were searched for qualified articles. The search mainly focused on three components: early-stage (0-III) BC, oral AHT administration, and adherence to AHT, with keywords derived from MeSH and entry terms. The factors identified were then classified into six categories based on a modified WHO multidimensional model. RESULTS: Overall, 146 studies were included; the median sample size was 651 (range, 31-40,009), and the mean age of the population was 61.5 years (standard deviation, 8.3 years). Patient- and therapy-related factors were the most frequently investigated factors. Necessity/concern beliefs and self-efficacy among patient-related factors were consistently related to better adherence than depression. Although drug side effects and medication use cannot be modified easily, a refined prescription strategy for the initiation and switching of AHT is likely to increase adherence levels. CONCLUSION: An effective psychological program that encourages positive views and beliefs about medication and management strategies for each therapy may be necessary to improve adherence to AHT. Social support and a sense of belonging can be enhanced through community participation and social media for better adherence to AHT. Patient-centered communication and appropriate recommendations by physicians may be attributable to better adherence outcomes. Findings from systematically organized factors that influence adherence to AHT may contribute to the establishment of intervention strategies to benefit patients with early-stage BC to achieve optimal health.

Radiation dose-event relationship after intraoperative radiotherapy as a boost in patients with breast cancer.

Purpose: Intraoperative radiotherapy (IORT) can be used as a boost in combination with external whole breast irradiation. This study reports the clinical and dosimetric factors associated with IORT-related adverse events (AE). Methods and materials: Between 2014 and 2021, 654 patients underwent IORT. A single fraction of 20 Gy was prescribed to the surface of the tumour cavity using the mobile 50-kV X-ray source. For skin dose measurement, at least four optically stimulated luminescent dosimeter (OSLD) chips were annealed and attached to the skin edge in the superior, inferior, medial, and lateral locations during IORT. Logistic regression analyses were conducted to identify factors associated with IORT-related AE. Results: With a median follow-up period of 42 months, 7 patients experienced local recurrence, resulting in a 4-year local failure-free survival rate of 97.9%. The median skin dose measured by OSLD was 3.85 Gy (range, 0.67-10.89 Gy), and a skin dose of > 6 Gy was observed in 38 patients (2%). The most common AE was seroma (90 patients, 13.8%). We also found that 25 patients (3.9%) experienced fat necrosis during follow-up, and among them, 8 patients underwent biopsy or excision to exclude local recurrence. IORT-related late skin injury occurred in 14 patients, and a skin dose > 6 Gy was significantly associated with IORT-induced skin injury (odds ratio 4.942, 95% confidence interval 1.294-18.871, p = 0.019). Conclusions: IORT was safely administered as a boost to various populations of patients with breast cancer. However, several patients may experience severe skin injuries, and for older patients with diabetes, IORT should be performed with caution.

Complications Including Capsular Contracture in Direct-to-Implant Breast Reconstruction With Textured Anatomical Versus Smooth Round Implants: A Single Center Retrospective Analysis.

PURPOSE: Implant-based breast reconstruction is the most common reconstruction method used after mastectomy in breast cancer patients. Many studies have compared the smooth round implants and textured anatomical implants. This study aimed to compare the complications, including capsular contracture, between these two implants used in direct-to-implant (DTI) breast reconstruction. METHODS: This retrospective chart review was performed using a prospectively maintained database from a single center. We identified patients who underwent mastectomy with DTI single-stage breast reconstruction at our hospital between August 2011 and June 2021. The overall complications, including capsular contracture, postoperative infection, seroma, hematoma, implant rupture, implant exposure, rippling, implant malposition, and nipple necrosis, were analyzed. RESULTS: In total, 340 breasts of 323 patients were reconstructed by the DTI approach using either textured anatomical (n = 203) or smooth round (n = 137) implants. The incidence of overall complications and capsular contracture was significantly lower with smooth round implants than with textured anatomical implants. Multivariate analysis showed that smooth round implants were associated with a reduced risk of overall complications (odds ratio [OR], 0.465; 95% confidence interval [CI], 0.265-0.813) and capsular contracture (OR, 0.475; 95% CI, 0.235-0.962). Particularly, smooth round implants were associated with a decreased risk of overall complications in patients not receiving adjuvant chemotherapy and a decreased risk of capsular contracture in patients with body mass index < 25 kg/m² and in those not receiving adjuvant radiotherapy. CONCLUSION: Smooth round implants demonstrated a decreased risk of overall complications and capsular contracture when compared with textured anatomical implants. These results may be utilized in counseling patients regarding the advantages and disadvantages of smooth round implants in DTI breast reconstruction.

Resolution of Nonmass Enhancement Extension to the Nipple at Breast MRI after Neoadjuvant Chemotherapy: Pathologic Response and Feasibility for Nipple-sparing Mastectomy.

Background Nipple-sparing mastectomy (NSM) is usually contraindicated in patients with nonmass enhancement (NME) extension to the nipple at breast MRI. However, little is known about the feasibility of NSM when NME extension to the nipple resolves after neoadjuvant chemotherapy (NAC). Purpose To evaluate whether NSM is an appropriate surgical procedure for patients in whom NME extension to the nipple resolves after NAC. Materials and Methods This retrospective study included 383 women with NME at baseline MRI who underwent NAC followed by mastectomy between January 2007 and March 2022 at a single institution. NME extension to the nipple was assessed using breast MRI before NAC (hereafter, pre-NAC) and after NAC (hereafter, post-NAC). In 326 women who underwent mastectomy with removal of the nipple-areolar complex, the rate of pathologic analysis-confirmed tumor invasion of the nipple compared with NME extension to the nipple at post-NAC breast MRI was evaluated. Tumor involvement of the nipple was also assessed in those with complete pathologic response at posttreatment MRI. Furthermore, the outcomes in 57 women undergoing NSM were investigated, particularly in patients with NME extension to the nipple at initial diagnosis. Results Of the 326 women who underwent mastectomy with removal of the nipple-areolar complex (mean age, 49 years ± 9.4 [SD]), 217 patients (67%) showed NME extension to the nipple on pre-NAC MRI scans. Among the 153 women (70%) in whom the NME extension to the nipple resolved after NAC, the rate of pathologic analysis-confirmed tumor invasion of the nipple was 2.6% (four of 153 women; 95% CI: 0, 6.5). No pathologic analysis-confirmed tumor invasion of the nipple was detected in 31 women with complete response at MRI. Of the 57 women who underwent NSM, 12 (21%) with resolution of NME extension to the nipple after NAC had no relapse during the median follow-up of 31 months (range, 11-80 months). Conclusion Pathologic analysis-confirmed tumor invasion of the nipple was rare in women with resolution of nonmass enhancement extension to the nipple after neoadjuvant chemotherapy (NAC). Therefore, nipple-sparing mastectomy could be feasible in this population, especially in those with complete MRI response to NAC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Lee in this issue.

Anaemia and pathologic complete response rate according to carboplatin dose in HER2+ breast cancer treated with neoadjuvant TCHP.

Grade 3/4 anaemia, which is mainly induced by carboplatin, frequently occurs in patients treated with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP). However, dose reduction of carboplatin may raise concerns about the oncological outcome. This study investigated the pathologic complete response (pCR) rate, occurrence of grade 3/4 anaemia, and transfusion rate according to carboplatin dose in patients treated with neoadjuvant TCHP. We retrospectively analysed 294 patients treated with neoadjuvant TCHP between April 2015 and December 2020. Case matching was performed using propensity score matching. Among patients treated with neoadjuvant TCHP, carboplatin area under the plasma concentration-time curve 6 (AUC6) was used in 234 patients (79.6%) and upfront carboplatin AUC5 was used in 60 patients (20.4%). No significant difference in pCR rate was found between the two groups (AUC6: 70.9%, AUC5: 80.0%). In both oestrogen receptor-positive (ER+) and ER- patients, no significant differences were observed between the AUC6 and AUC5 groups (ER+: 54.3% vs. 50.0%, ER-: 81.7% vs. 86.0%). The case-matched cohort showed consistent findings. The AUC5 group had lower frequencies of grade 3/4 anaemia (18.3% vs. 34.2%) and transfusion events (10.0% vs. 21.8%) than the AUC6 group. Compared with AUC5, carboplatin at AUC6 would associate with a 2.7-fold increased risk of grade 3 or 4 chemotherapy-induced anaemia. Carboplatin AUC5 has comparable cytotoxic effects to carboplatin AUC6 in patients with HER2+ breast cancer treated with six cycles of neoadjuvant TCHP, with fewer complications associated with clinically meaningful anaemia. AUC5 may be the optimal carboplatin dose to reduce TCHP-induced anaemia in patients with HER2+ breast cancer treated with TCHP.

18F-FDG uptake of visceral adipose tissue on preoperative PET/CT as a predictive marker for breast cancer recurrence.

Glucose utilization by visceral adipose tissue (VAT) reflects inflammatory activity, which also promotes tumor growth and carcinogenesis. The effect of metabolically active VAT on survival outcomes in breast cancer is unknown. We investigated survival outcomes in patients with breast cancer based on the standardized uptake value (SUV) of VAT (SUVmean-VAT) using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). A total of 148 patients with breast cancer were divided into high- and low groups according to their SUVmean-VAT and SUVmax-tumor. Clinical characteristics and survival outcomes were compared between the groups. High SUVmean-VAT was associated with poor recurrence-free survival (RFS; hazard ratio [HR], 2.754; 95% confidence interval [CI], 1.090-6.958, p = 0.032) and distant metastasis-free survival (DMFS; HR, 3.500; 95% CI, 1.224-10.01, p = 0.019). Multivariate analysis showed that high SUVmean-VAT was a significant factor for poor RFS and poor DMFS (p = 0.023 and 0.039, respectively). High SUVmax-tumor was significantly associated with short RFS (p = 0.0388). Tumors with a high SUV tended to have a short DMFS, although the difference was not significant (p = 0.0718). Our findings showed that upregulated glucose metabolism in the VAT measured using 18F-FDG PET/CT may be a prognostic biomarker for adverse outcomes in breast cancer.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Early Standardized Uptake Value Reduction in Patients With Breast Cancer Receiving Neoadjuvant Chemotherapy.

PURPOSE: We investigated the treatment response and prognosis using the neutrophil-to-lymphocyte ratio (NLR) and standardized uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in neoadjuvant settings. METHODS: Baseline NLR and maximum SUV (SUVmax) were retrospectively analyzed in 273 females with breast cancer who received neoadjuvant chemotherapy followed by surgery. Of these, 101 patients underwent 18F-FDG PET after 3-4 neoadjuvant chemotherapy cycles, which allowed the measurement of ΔSUVmax, an early reduction in SUVmax. NLR and early SUVmax reduction (ΔSUVmax) were classified as low and high, respectively, relative to the median values. RESULTS: The mean NLR was lower, and the mean ΔSUVmax was higher in patients with pathologic complete response (pCR) than in those with residual tumors. The ΔSUVmax was an independent variable associated with pCR. Furthermore, the high NLR group had poor recurrence-free survival (RFS) and overall survival. Among patients with ΔSUVmax data, high NLR (adjusted hazard ratio, 2.82; 95% confidence intervals [CI], 1.26-6.28; P = 0.016) and low ΔSUVmax (adjusted hazard ratio, 2.39; 95% CI, 1.07-5.34; P = 0.037) were independent prognostic factors for poor RFS. The categorization of the patients into four groups according to the combination of NLR and ΔSUVmax showed that patients with high NLR and low ΔSUVmax had significantly poorer RFS. CONCLUSION: Baseline NLR and ΔSUVmax were significantly associated with the prognosis of patients with breast cancer who received neoadjuvant chemotherapy. These results suggest that metabolic non-responders with defective immune systems have worse survival outcomes.

Association of Body Mass Index With 21-Gene Recurrence Score Among Women With Estrogen Receptor-Positive, ERBB2-Negative Breast Cancer.

Importance: Body mass index (BMI) may affect the 21-gene recurrence score (RS) in patients with ER-positive, ERBB2-negative breast cancer. If high BMI increases genomic risk in ER-positive, ERBB2-negative breast cancer, weight control will become more important. Objective: To assess the association between RS and BMI according to age groups and address BMI as a factor associated with high RS. Design, Setting, and Participants: This cohort study included 2295 patients with ER-positive, ERBB2-negative breast cancer who had undergone a multigene assay between March 29, 2010, and December 31, 2020, in 2 hospitals. All of the study patients were Korean women, and the median follow-up period was 45 months (range, 1-40 months). The correlations between continuous RS and BMI were investigated. A high BMI was defined as a body mass index greater than or equal to 25. In the younger age group (age ≤45 years), a high RS was defined as an RS of greater than 20. Exposures: Body mass index. Main Outcomes and Measures: The Pearson correlation coefficient was used to estimate the association between RS and BMI. A multivariable binary logistic model was used to identify high RS. Results: Among the 2295 women included (mean [SD] age, 49.8 [4.00] years; range, 22-81 years), 776 were aged 45 years or younger; RS and BMI were weakly correlated (correlation coefficient, 0.119; P < .001) in this younger group. Among them, the proportion of patients with an RS greater than 20 was significantly higher in the high BMI group than in the normal BMI group (45.5% [46 of 101] vs 27.3% [184 of 675]; P < .001). In the multivariable analysis, high BMI was an associated factor for high RS (odds ratio, 2.06; 95% CI, 1.28-3.32; P = .003). The 21-gene multigene assay-guided chemotherapy rate was significantly higher in patients with high BMI (30.7% [31 of 101] vs 20.2% [136 of 674]; P = .02). Conclusions and Relevance: In this cohort study of women aged 45 years or younger, high BMI was associated with higher RS in those with ER-positive, ERBB2-negative breast cancer; further studies are necessary to examine the underlying mechanisms.