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Kim L, Coman M, Pusztai L, Park TS. Neoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest. Ann Surg Oncol 2023; 30:6441-6449. [PMID: 37349612 DOI: 10.1245/s10434-023-13714-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 05/23/2023] [Indexed: 06/24/2023]
Abstract
Despite breast cancer being long thought to be "immunologically cold," within early, triple-negative breast cancer (TNBC), there has been exciting advances with the use of immune checkpoint modulation combined with neoadjuvant chemotherapy. We review the major trials that have investigated combination immunochemotherapy in the neoadjuvant setting, reviewing both the pathological complete response rates and the maturing data regarding event-free and overall survival. Strategies to deescalate adjuvant therapy in patients with preserving excellent clinical outcome, as well as exploration of combinatorial adjuvant therapies to improve outcome in those with extensive residual are the next-generation challenges. In addition to refinement of existing biomarkers, such as PD-L1, TILs, and tumor mutational burden (TMB), exploration of topics like the microbiome as both a biomarker and a therapeutic has shown promise in other cancer types, which motivates investigating these in breast cancer.
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Affiliation(s)
- Leah Kim
- Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Magdalena Coman
- Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA
| | - Lajos Pusztai
- Yale School of Medicine, Yale Cancer Center, New Haven, CT, USA
| | - Tristen S Park
- Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, CT, USA.
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Devoy C, Flores Bueso Y, Tangney M. Understanding and harnessing triple-negative breast cancer-related microbiota in oncology. Front Oncol 2022; 12:1020121. [PMID: 36505861 PMCID: PMC9730816 DOI: 10.3389/fonc.2022.1020121] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 10/31/2022] [Indexed: 11/27/2022] Open
Abstract
Bacterial inhabitants of the body have the potential to play a role in various stages of cancer initiation, progression, and treatment. These bacteria may be distal to the primary tumour, such as gut microbiota, or local to the tissue, before or after tumour growth. Breast cancer is well studied in this context. Amongst breast cancer types, Triple Negative Breast Cancer (TNBC) is more aggressive, has fewer treatment options than receptor-positive breast cancers, has an overall worse prognosis and higher rates of reoccurrence. Thus, an in-depth understanding of the bacterial influence on TNBC progression and treatment is of high value. In this regard, the Gut Microbiota (GM) can be involved in various stages of tumour progression. It may suppress or promote carcinogenesis through the release of carcinogenic metabolites, sustenance of proinflammatory environments and/or the promotion of epigenetic changes in our genome. It can also mediate metastasis and reoccurrence through interactions with the immune system and has been recently shown to influence chemo-, radio-, and immune-therapies. Furthermore, bacteria have also been found to reside in normal and malignant breast tissue. Several studies have now described the breast and breast tumour microbiome, with the tumour microbiota of TNBC having the least taxonomic diversity among all breast cancer types. Here, specific conditions of the tumour microenvironment (TME) - low O2, leaky vasculature and immune suppression - are supportive of tumour selective bacterial growth. This innate bacterial ability could enable their use as delivery agents for various therapeutics or as diagnostics. This review aims to examine the current knowledge on bacterial relevance to TNBC and potential uses while examining some of the remaining unanswered questions regarding mechanisms underpinning observed effects.
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Affiliation(s)
- Ciaran Devoy
- Cancer Research@UCC, College of Medicine and Health, University College Cork, Cork, Ireland,SynBio Center, University College Cork, Cork, Ireland,APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Yensi Flores Bueso
- Cancer Research@UCC, College of Medicine and Health, University College Cork, Cork, Ireland,SynBio Center, University College Cork, Cork, Ireland,APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Mark Tangney
- Cancer Research@UCC, College of Medicine and Health, University College Cork, Cork, Ireland,SynBio Center, University College Cork, Cork, Ireland,APC Microbiome Ireland, University College Cork, Cork, Ireland,School of Pharmacy, College of Medicine and Health, University College Cork, Cork, Ireland,*Correspondence: Mark Tangney,
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Zhou H, Yuan Y, Wang H, Xiang W, Li S, Zheng H, Wen Y, Ming Y, Chen L, Zhou J. Gut Microbiota: A Potential Target for Cancer Interventions. Cancer Manag Res 2021; 13:8281-8296. [PMID: 34764691 PMCID: PMC8572730 DOI: 10.2147/cmar.s328249] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota plays a crucial role in many physiological processes in the human body. Dysbiosis can disrupt the intestinal barrier and alter metabolism and immune responses, leading to the development of diseases. Over the past few decades, evidence has accumulated linking changes in the composition of the gut microbiota to dozens of seemingly unrelated conditions, including cancer. Overall, the gut microbiota mainly affects the occurrence and development of cancer by damaging host DNA, forming and maintaining a pro-inflammatory environment, and affecting host immune responses. In addition, the gut microbiota can also affect the efficacy and toxicity of chemotherapy, radiotherapy, and immunotherapy. Scientists attempt to improve the efficacy and decrease the toxicity of these treatment modalities by fine-tuning the gut microbiota. The aim of this review is to assist researchers and clinicians in developing new strategies for the detection and treatment of tumors by providing the latest information on the intestinal microbiome and cancer, as well as exploring potential application prospects and mechanisms of action.
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Affiliation(s)
- Hu Zhou
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Yuan Yuan
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China.,Department of Operation and Anaesthesia, Yibin First People's Hospital, Yibin, Sichuan, People's Republic of China
| | - Haorun Wang
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Wei Xiang
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Shenjie Li
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Haowen Zheng
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Yuqi Wen
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Yang Ming
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China
| | - Ligang Chen
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China.,Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People's Republic of China.,Neurological Diseases and Brain Function Laboratory, Luzhou, Sichuan, People's Republic of China
| | - Jie Zhou
- Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.,Sichuan Clinical Research Center for Neurosurgery, Luzhou, Sichuan, People's Republic of China.,Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People's Republic of China.,Neurological Diseases and Brain Function Laboratory, Luzhou, Sichuan, People's Republic of China
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