A Look at the Other Side: High-Risk Lesions and Occult Contralateral Malignancy in Symmetry Procedures for Patients Undergoing Oncoplastic Breast-Conserving Surgery.

BACKGROUND: The incidence of occult breast cancer among patients undergoing reduction mammoplasty or risk-reducing mastectomies ranges from 1% to approximately 10%, respectively. Identification of incidental cancer often mandates subsequent mastectomy due to ambiguous margins. This study aimed to determine the incidence of contralateral malignancy among patients undergoing oncoplastic breast-conserving surgery (OBCS) with concurrent symmetry procedures. METHODS: The authors reviewed their prospectively maintained institutional database of patients with unilateral breast cancer who underwent OBCS. Patients who underwent excisional biopsy on the contralateral breast were analyzed separately. Patient demographics, pathologic features, and subsequent disease management were evaluated. RESULTS: Between March 2018 and July 2022, 289 patients underwent OBCS with a symmetry procedure, and 100 patients yielded contralateral breast tissue specimens. For 14 patients, a planned excisional biopsy was performed with their symmetry procedure, and five lesions (36%) were found to be malignant. Of the remaining 86 patients, 92% underwent preoperative breast magnetic resonance imaging (MRI). Four patients (4.7%) had occult malignancies identified on the contralateral breast pathology; three patients with ductal carcinoma in situ and one patient with invasive lobular carcinoma. Three patients had undergone preoperative MRI without suspicious findings. No patients required mastectomy for treatment of the contralateral breast cancer. CONCLUSION: The incidence of occult malignancy among OBCS symmetry procedures approaches 5%. The final pathology of excisional biopsies had a higher upgrade rate than previously reported. All identified malignancies were early-stage disease. The higher incidence of occult breast cancer in this population warrants the routine orientation of all specimens, which allows patients with incidental early-stage cancer the option of breast preservation.

Impact of Locoregional Treatment on Survival in Young Patients with Early-Stage Breast Cancer undergoing Upfront Surgery.

BACKGROUND: Randomized, controlled trials comparing breast-conserving therapy (BCT) with mastectomy have demonstrated equivalent overall survival (OS), but recent observational studies have shown improved OS in patients undergoing BCT. These studies provide limited data on young patients who are traditionally offered mastectomy due to perceived higher disease risk. This study examines the OS in a contemporary series of young women with breast cancer undergoing upfront BCT compared with mastectomy. METHODS: Women ≤40 years old with primary invasive T1-T2, N0-N1 breast cancer were identified from the National Cancer Database between 2006 and 2016. Patient cohorts were based according to locoregional treatment: BCT, mastectomy alone (Mx), and mastectomy with radiotherapy (Mx/RT). Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability of treatment weighting (IPTW) were performed to account for treatment selection bias effects in OS. RESULTS: A total of 15,611 patients met the study criteria; 9,509 patients (60.9%) had BCT, 4,020 (25.8%) had Mx/RT, and 2,082 (13.3%) had Mx alone. The median follow-up was 4.6 years (interquartile range [IQR] 3.0-6.4). After IPTW-adjustment, the 5-year OS was similar for BCT (95%), Mx (95%), and Mx/RT (94%), and there was no significant difference in OS in Mx (hazard ratio [HR] = 1.16, 95% confidence interval [CI] 0.90-1.51) and Mx/RT (HR = 1.08, 95% CI 0.88-1.34) compared with BCT. Mx/RT was associated with decreased survival in patients with pT2N0 (HR = 1.78, 95% CI 1.12-2.84). CONCLUSIONS: Among young patients with early-stage breast cancer, overall survival was equivalent regardless of surgical approach. Breast-conserving therapy remains a safe option in young women despite the clinical tendency to offer upfront mastectomy in young patients.

Is the 21-Gene Recurrence Score on Core Needle Biopsy Equivalent to Surgical Specimen in Early-Stage Breast Cancer? A Comparison of Gene Expression Between Paired Core Needle Biopsy and Surgical Specimens.

BACKGROUND: Molecular testing on surgical specimens predicts disease recurrence and benefit of adjuvant chemotherapy in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (EBC). Testing on core biopsies has become common practice despite limited evidence of concordance between core/surgical samples. In this study, we compared the gene expression of the 21 genes and the recurrence score (RS) between paired core/surgical specimens. METHODS: Eighty patients with HR+/HER2- EBC were evaluated from two publicly available gene expression datasets (GSE73235, GSE76728) with paired core/surgical specimens without neoadjuvant systemic therapy. The expression of the 21 genes was compared in paired samples. A microarray-based RS was calculated and a value ≥ 26 was defined as high-RS. The concordance rate and kappa statistic were used to evaluate the agreement between the RS of paired samples. RESULTS: Overall, there was no significant difference and a high correlation in the gene expression levels of the 21 genes between paired samples. However, CD68 and RPLP0 in GSE73235, AURKA, BAG1, and TFRC in GSE76728, and MYLBL2 and ACTB in both datasets exhibited weak to moderate correlation (r < 0.5). There was a high correlation of the microarray-based RS between paired samples in GSE76728 (r = 0.91, 95% confidence interval [CI] 0.81-0.96) and GSE73235 (r = 0.82, 95% CI 0.71-0.89). There were no changes in RS category in GSE76728, whereas 82% of patients remained in the same RS category in GSE73235 (κ = 0.64). CONCLUSIONS: Gene expression levels of the 21-gene RS showed a high correlation between paired specimens. Potential sampling and biological variability on a set of genes need to be considered to better estimate the RS from core needle biopsy.

Clinical Implications of Transcriptomic Changes After Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer.

BACKGROUND: Pathological response to neoadjuvant chemotherapy (NAC) is critical in prognosis and selection of systemic treatments for patients with triple-negative breast cancer (TNBC). The aim of this study is to identify gene expression-based markers to predict response to NAC. PATIENTS AND METHODS: A survey of 43 publicly available gene expression datasets was performed. We identified a cohort of TNBC patients treated with NAC (n = 708). Gene expression data from different studies were renormalized, and the differences between pretreatment (pre-NAC), on-treatment (post-C1), and surgical (Sx) specimens were evaluated. Euclidean statistical distances were calculated to estimate changes in gene expression patterns induced by NAC. Hierarchical clustering and pathway enrichment analyses were used to characterize relationships between differentially expressed genes and affected gene pathways. Machine learning was employed to refine a gene expression signature with the potential to predict response to NAC. RESULTS: Forty nine genes consistently affected by NAC were involved in enhanced regulation of wound response, chemokine release, cell division, and decreased programmed cell death in residual invasive disease. The statistical distances between pre-NAC and post-C1 significantly predicted pathological complete response [area under the curve (AUC) = 0.75; p = 0.003; 95% confidence interval (CI) 0.58-0.92]. Finally, the expression of CCND1, a cyclin that forms complexes with CDK4/6 to promote the cell cycle, was the most informative feature in pre-NAC biopsies to predict response to NAC. CONCLUSIONS: The results of this study reveal significant transcriptomic changes induced by NAC and suggest that chemotherapy-induced gene expression changes observed early in therapy may be good predictors of response to NAC.

Biological effects of intraoperative radiation therapy: histopathological changes and immunomodulation in breast cancer patients.

Introduction: Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Methods: Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Results: Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. Conclusion: IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.

Accuracy of predicting axillary lymph node positivity by physical examination, mammography, ultrasonography, and magnetic resonance imaging.

BACKGROUND: Axillary lymph node status continues to be among the most important prognostic variables regarding breast cancer survival. We were interested in our ability to accurately predict axillary nodal involvement by using physical examination and standard breast imaging studies in combination. METHODS: A retrospective review was performed of 244 consecutive patients diagnosed with invasive breast carcinoma between May 2008 and December 2010 who underwent physical examination of the axilla, digital mammography, axillary ultrasonography, and contrast-enhanced breast magnetic resonance imaging and who had subsequent histopathologic evaluation of one or more axillary lymph nodes. RESULTS: A total of 62 (25%) of 244 women were found to have positive axillary lymph nodes on final histopathologic examination, 42% of whom were able to be identified preoperatively. The sensitivity for predicting axillary metastasis if any one or more examination modalities were suspicious was 56.5%. The specificity for predicting axillary metastasis if any three or more modalities were suspicious was 100%. Of the patients who had all four modalities negative, 14% were ultimately found to have histologically positive nodes at the time of surgery. CONCLUSIONS: Physical examination and multimodal imaging in combination are useful for preoperative axillary staging and treatment planning. However, they remain inadequate definitive predictors of axillary lymph node involvement.