A pharmacophore‐based classification better predicts the outcomes of HER2‐negative breast cancer patients receiving the anthracycline‐ and/or taxane‐based neoadjuvant chemotherapy

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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Sentinel node biopsy in post‐neoadjuvant chemotherapy breast cancer patients using preoperative breast tattooing—A novel technique

The Breast Journal ◽

10.1111/tbj.14167 ◽

2021 ◽

Author(s):

Rexeena V. Bhargavan ◽

Paul Augustine ◽

Jagath K. M. Krishna ◽

Neelima Radhakrishnan

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Sentinel Node ◽

Cancer Patients ◽

Sentinel Node Biopsy ◽

Breast Cancer Patients ◽

Novel Technique ◽

Node Biopsy

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Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00237-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Xu Yang ◽

Geng-Xi Cai ◽

Bo-Wei Han ◽

Zhi-Wei Guo ◽

Ying-Song Wu ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Cell Receptor ◽

Chemotherapy Response ◽

Breast Cancer Patients ◽

Plasma Dna ◽

Transcription Start Sites ◽

Response To Chemotherapy

AbstractGene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.

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Feasibility and reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer patients with positive axillary nodes at initial diagnosis: An up-to date meta-analysis of 3,578 patients

The Breast ◽

10.1016/j.breast.2021.07.015 ◽

2021 ◽

Author(s):

Siyang Cao ◽

Xia Liu ◽

Junwei Cui ◽

Xiaoling Liu ◽

Jieyu Zhong ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Sentinel Lymph Node ◽

Sentinel Lymph Node Biopsy ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Meta Analysis ◽

Lymph Node Biopsy ◽

Breast Cancer Patients ◽

Node Biopsy

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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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