Gut Microbiota Condition the Therapeutic Efficacy of Trastuzumab in HER2-Positive Breast Cancer

Modica, Martina Di; Gargari, Giorgio; Regondi, Viola; Bonizzi, Arianna; Arioli, Stefania; Belmonte, Beatrice; Cecco, Loris De; Fasano, Elena; Bianchi, Francesca; Bertolotti, Alessia; Tripodo, Claudio; Villani, Laura; Corsi, Fabio; Guglielmetti, Simone; Balsari, Andrea; Triulzi, Tiziana; Tagliabue, Elda

doi:10.1158/0008-5472.can-20-1659

Cited by 100 publications

(77 citation statements)

References 52 publications

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“…Terrisse et al 62 found that chemotherapy drastically shifted the microbiome composition, by reducing abundance of microflora associated with side effects and increasing abundance of favorable commensals after adjuvant or neoadjuvant treatment with anthracylines and taxanes. A study by Di Modica et al 63 revealed the existence of specific microbiota in patients with Her2+ breast cancer that can influence their response to targeted therapy. This suggests that manipulation of the fecal microbiota is an optimal future regimen to achieve effective treatment or to explore its potential as a biomarker for therapeutic response.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Gut Microbiota in Patients with Benign and Malignant Breast Tumors: A Pilot Study

Yang

Wang

Peng

et al. 2021

Evol Bioinform Online

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The microbiome plays diverse roles in many diseases and can potentially contribute to cancer development. Breast cancer is the most commonly diagnosed cancer in women worldwide. Thus, we investigated whether the gut microbiota differs between patients with breast carcinoma and those with benign tumors. The DNA of the fecal microbiota community was detected by Illumina sequencing and the taxonomy of 16S rRNA genes. The α-diversity and β-diversity analyses were used to determine richness and evenness of the gut microbiota. Gene function prediction of the microbiota in patients with benign and malignant carcinoma was performed using PICRUSt. There was no significant difference in the α-diversity between patients with benign and malignant tumors ( P = 3.15e−1 for the Chao index and P = 3.1e−1 for the ACE index). The microbiota composition was different between the 2 groups, although no statistical difference was observed in β-diversity. Of the 31 different genera compared between the 2 groups, level of only Citrobacter was significantly higher in the malignant tumor group than that in benign tumor group. The metabolic pathways of the gut microbiome in the malignant tumor group were significantly different from those in benign tumor group. Furthermore, the study establishes the distinct richness of the gut microbiome in patients with breast cancer with different clinicopathological factors, including ER, PR, Ki-67 level, Her2 status, and tumor grade. These findings suggest that the gut microbiome may be useful for the diagnosis and treatment of malignant breast carcinoma.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Gut Microbiota in Patients with Benign and Malignant Breast Tumors: A Pilot Study

Yang

Wang

Peng

et al. 2021

Evol Bioinform Online

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“…[103] Bacterial enzymes can degrade specific chemotherapy compounds into non-functional byproducts, [47] diminishing drug responses in colonized patients. In mouse models of HER2-positive breast cancer, antibiotic administration impairs trastuzumab efficacy and clinical patients with less diverse gut microbiomes are less likely to respond to trastuzumab; [68] moreover, fecal microbiota transplants from patient responders and non-responders into recipient mice recapitulate differential response to trastuzumab in patients, implicating gut microbiota as critical for HER2-targeted therapeutic responses. [68] Gut microbiota also affect hormonal therapies.…”

Section: Prognostics and Companion Diagnosticsmentioning

confidence: 99%

“…In mouse models of HER2-positive breast cancer, antibiotic administration impairs trastuzumab efficacy and clinical patients with less diverse gut microbiomes are less likely to respond to trastuzumab; [68] moreover, fecal microbiota transplants from patient responders and non-responders into recipient mice recapitulate differential response to trastuzumab in patients, implicating gut microbiota as critical for HER2-targeted therapeutic responses. [68] Gut microbiota also affect hormonal therapies. Administration of abiraterone acetate (AA) in the setting of castrate-resistant prostate cancer promoted outgrowth of Akkermansia muciniphila and appeared to aid overall AA therapeutic efficacy.…”

Section: Prognostics and Companion Diagnosticsmentioning

confidence: 99%

Cancer's second genome: Microbial cancer diagnostics and redefining clonal evolution as a multispecies process

et al. 2022

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The presence and role of microbes in human cancers has come full circle in the last century. Tumors are no longer considered aseptic, but implications for cancer biology and oncology remain underappreciated. Opportunities to identify and build translational diagnostics, prognostics, and therapeutics that exploit cancer's second genome—the metagenome—are manifold, but require careful consideration of microbial experimental idiosyncrasies that are distinct from host‐centric methods. Furthermore, the discoveries of intracellular and intra‐metastatic cancer bacteria necessitate fundamental changes in describing clonal evolution and selection, reflecting bidirectional interactions with non‐human residents. Reconsidering cancer clonality as a multispecies process similarly holds key implications for understanding metastasis and prognosing therapeutic resistance while providing rational guidance for the next generation of bacterial cancer therapies. Guided by these new findings and challenges, this Review describes opportunities to exploit cancer's metagenome in oncology and proposes an evolutionary framework as a first step towards modeling multispecies cancer clonality. Also see the video abstract here: https://youtu.be/-WDtIRJYZSs

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“…Recently, Di Modica et al analysed the gut microbiota composition of a group of breast cancer patients who responded favourably to adjuvant treatment with Trastuzumab. They found that in those patients with favourable results in response to treatment, Clostridiales ( Lachnospiraceae ), Bifidobacteriaceae , Turicibacteraceae, and Bacteroidales ( Prevotellaceae ) predominated, while in the other group of patients who did not respond to treatment, an enrichment in the phylum Bacteroidetes ( Bacteroidia ) was observed [ 95 ].…”

Section: Modulation Of Antitumoural Therapies Efficacy and Toxicity By Gut Microbiotamentioning

confidence: 99%

Gut and Endometrial Microbiome Dysbiosis: A New Emergent Risk Factor for Endometrial Cancer

Boutriq

González-González

Plaza-Andrades

et al. 2021

JPM

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Endometrial cancer is one of the most common gynaecological malignancies worldwide. Histologically, two types of endometrial cancer with morphological and molecular differences and also therapeutic implications have been identified. Type I endometrial cancer has an endometrioid morphology and is estrogen-dependent, while Type II appears with non-endometrioid differentiation and follows an estrogen-unrelated pathway. Understanding the molecular biology and genetics of endometrial cancer is crucial for its prognosis and the development of novel therapies for its treatment. However, until now, scant attention has been paid to environmental components like the microbiome. Recently, due to emerging evidence that the uterus is not a sterile cavity, some studies have begun to investigate the composition of the endometrial microbiome and its role in endometrial cancer. In this review, we summarize the current state of this line of investigation, focusing on the relationship between gut and endometrial microbiome and inflammation, estrogen metabolism, and different endometrial cancer therapies.

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Gut Microbiota Condition the Therapeutic Efficacy of Trastuzumab in HER2-Positive Breast Cancer

Abstract: Running title: Gut microbiota implication in response to trastuzumab therapy.

Cited by 100 publications

References 52 publications

Comparison of the Gut Microbiota in Patients with Benign and Malignant Breast Tumors: A Pilot Study

Comparison of the Gut Microbiota in Patients with Benign and Malignant Breast Tumors: A Pilot Study

Cancer's second genome: Microbial cancer diagnostics and redefining clonal evolution as a multispecies process

Gut and Endometrial Microbiome Dysbiosis: A New Emergent Risk Factor for Endometrial Cancer

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