Stability and Prognostic Value of Slug, Sox9 and Sox10 Expression in Breast Cancers Treated with Neoadjuvant Chemotherapy

The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

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Is There a Bias Against Obese Patients in the Treatment of Breast Cancer?

The American Surgeon ◽

10.1177/0003134820984877 ◽

2020 ◽

pp. 000313482098487

Author(s):

Melinda Wang ◽

Julian Huang ◽

Anees B. Chagpar

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Prophylactic Mastectomy ◽

Implicit Bias ◽

Treatment Decision ◽

Obese Patients ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Immediate Reconstruction

Background Patient and tumor characteristics often coincide with obesity, potentially affecting treatment decision-making in obese breast cancer patients. Independent of all of these factors, however, it is unclear whether obesity itself impacts the decision to offer patients undergoing mastectomy breast reconstruction, postmastectomy radiation therapy (PMRT), or neoadjuvant chemotherapy. We sought to determine whether implicit bias against obese breast cancer patients undergoing mastectomy plays a role in their treatment. Methods Medical records of breast cancer patients undergoing mastectomy from January 2010 to April 2018 from a single institution were retrospectively reviewed, separated into obese (BMI ≥30) and nonobese (BMI <30) categories, and compared using nonparametric statistical analyses. Results Of 972 patients, 291 (31.2%) were obese. Obese patients were more likely to have node-positive, triple-negative breast cancers ( P = .026) and were also more likely to have other comorbidities such as a history of smoking ( P = .026), hypertension ( P < .001), and diabetes ( P < .001). Receipt of immediate reconstruction and contralateral prophylactic mastectomy did not vary between obese and nonobese patients. While obese patients were more likely to undergo neoadjuvant chemotherapy (26.5% vs. 18.1%, P = .004) and PMRT (33.0% vs. 23.4%, P = .003), this did not remain significant when controlling for comorbidities and clinicopathologic confounders. Conclusion Obese patients present with more aggressive tumors and often have concomitant comorbidities. Independent of these factors, however, differences in the treatment of patients undergoing mastectomy do not seem to be affected by an implicit bias against obese patients.

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Radiopaque coil insertion into breast cancers prior to neoadjuvant chemotherapy

The Breast ◽

10.1016/j.breast.2004.08.008 ◽

2005 ◽

Vol 14 (2) ◽

pp. 108-117 ◽

Cited By ~ 5

Author(s):

Ali R. Sever ◽

Mary E.R. O’Brien ◽

Stephen Humphreys ◽

Inderjit Singh ◽

Susan E. Jones ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Breast Cancers

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Molecular profiles of genomically high risk ER+ HER2- breast cancer tumors classified as functionally basal or luminal B by the 80-gene signature.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.563 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 563-563

Author(s):

Joyce O'Shaughnessy ◽

Virginia G. Kaklamani ◽

Yuan Yuan ◽

Julie Barone ◽

Sami Diab ◽

...

Keyword(s):

Cell Proliferation ◽

High Risk ◽

Neoadjuvant Chemotherapy ◽

Enrichment Analysis ◽

Gene Signature ◽

Breast Cancers ◽

Luminal B ◽

Estrogen Response ◽

Luminal Type ◽

Basal Type

563 Background: The 80-gene signature (BluePrint/BP) classifies early-stage breast cancers based on functional molecular pathways as luminal, HER2, or Basal-type. In the NBRST study, 13% of immunochemistry (IHC) defined ER+ HER2- cancers reclassified as Basal-type by the BP assay (ER+ Basal), and these had worse prognosis but responded better to neoadjuvant chemotherapy than ER+ HER2- cancers classified as genomically luminal-type. The 70-gene risk of recurrence signature (MammaPrint/MP) further stratifies luminal-type cancers into low risk luminal A or high risk (HR) luminal B. HR cancers can be further stratified into High 1 (H1) or High 2 (H2), and the I-SPY2 trial has shown higher pCR rates in ER+ cancers classified as H2. Here, we investigated biological differences among ER+ Basal, ER- Basal, H1 luminal B, and H2 luminal B cancers by full transcriptome analysis. Methods: From the FLEX Study (NCT03053193), 1501 breast cancers with known IHC ER status were classified by MP and BP: 103 ER+ Basal, 210 ER- Basal and 1188 luminal B (H1 n=1034, H2 n=154). Clinical factors were assessed by either the Chi-square or Fisher’s exact tests; ANOVA or t test were used to analyze age. Differentially expressed genes (DEGs) were detected using Limma and pathway analyses were performed with GSEA. DEGs with a fold change >2 and FDR < 0.05 were considered significant. Results: Basal-type cancers (ER+/ER-) were larger and higher grade than luminal B cancers. Clustering analysis showed similar transcriptional profiles between ER+ Basal and ER- Basal cancers, distinct from luminal B cancers. Few DEGs were detected between ER+ Basal and ER- Basal cancers, and significantly more DEGs were found between ER+ Basal and luminal B cancers. Only three upregulated genes were detected in ER+ Basal compared to ER- Basal cancers: ESR1 and two immune-related genes ( FDCSP and LTF). Enrichment analysis of DEGs indicated increased immune activation and cell proliferation in ER+ Basal and ER- Basal cancers, and decreased estrogen response between ER+ Basal and luminal B cancers. Enrichment analysis between luminal B H1 and H2 cancers showed H2 cancers had higher immune activation and cell proliferation and lower estrogen response. Conclusions: Reclassification by BP of IHC defined ER+ HER2- cancers identified a subgroup of ER+ cancers that are biologically closer to ER- Basal than luminal-type cancers. Significant differences in response to neoadjuvant chemotherapy that have been seen between ER+ Basal and luminal B breast cancers lend support to the clinical importance of these findings. These data explain the poor prognosis observed in patients with ER+ Basal cancers and suggest that optimized chemotherapy, such as that for triple negative cancer, might be of benefit. BP provides clinically actionable information beyond pathological subtyping, which may guide neoadjuvant treatment recommendations. Clinical trial information: NCT03053193.

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