Risk of chemotherapy-related amenorrhoea (CRA) in premenopausal women undergoing chemotherapy for early stage breast cancer.

PURPOSE: While chemotherapy has improved survival among younger women with breast cancer, it can induce temporary or permanent chemotherapy-related amenorrhoea (CRA), impacting survival benefit, quality of life and, importantly for younger patients, fertility. METHODS: This single institution retrospective study of 107 premenopausal women with early stage breast cancer who received neoadjuvant or adjuvant combined chemotherapy treatment investigates the association of clinicopathological factors (including age-related, gynaecological and tumour-related variables) with CRA and resumption of menses using generalised linear models for univariable and multivariate analyses. RESULTS: 76% of women developed CRA, of which only 40% resumed menses after treatment. Age at time of treatment and at menarche were significantly associated with CRA incidence, with higher rates linked to older age (≥ 40 years) and later menarche (at ≥ 13 years), in both univariable (P = 0.043 and P = 0.009, respectively) and multivariate (P = 0.010 and P = 0.012, respectively) analyses. Age at time of treatment, age at menarche and use of tamoxifen were significantly associated with resumption of menses (with greater resumption rates linked to younger age (< 40 years old), later menarche (≥ 13 years old) or no tamoxifen use status), in both univariable (P < 0.0001, P = 0.002 and P = 0.039, respectively) and multivariate (P = 0.001, P = 0.011 and P = 0.008, respectively) analyses. Menses resumption rates were also significantly higher (P = 0.015) in women with later cessation of menses (after 3-6 chemotherapy cycles rather than sooner). CONCLUSIONS: Age at menarche and, specially, at time of treatment are important risk factors for CRA. These variables could aid decision-making for treatment selection and fertility preservation among premenopausal women with early breast cancer.

Current trends in the treatment of HR+/HER2+ breast cancer.

Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.

Unlocking the transcriptomic potential of formalin-fixed paraffin embedded clinical tissues: comparison of gene expression profiling approaches.

BACKGROUND: High-throughput transcriptomics has matured into a very well established and widely utilised research tool over the last two decades. Clinical datasets generated on a range of different platforms continue to be deposited in public repositories provide an ever-growing, valuable resource for reanalysis. Cost and tissue availability normally preclude processing samples across multiple technologies, making it challenging to directly evaluate performance and whether data from different platforms can be reliably compared or integrated. METHODS: This study describes our experiences of nine new and established mRNA profiling techniques including Lexogen QuantSeq, Qiagen QiaSeq, BioSpyder TempO-Seq, Ion AmpliSeq, Nanostring, Affymetrix Clariom S or U133A, Illumina BeadChip and RNA-seq of formalin-fixed paraffin embedded (FFPE) and fresh frozen (FF) sequential patient-matched breast tumour samples. RESULTS: The number of genes represented and reliability varied between the platforms, but overall all methods provided data which were largely comparable. Crucially we found that it is possible to integrate data for combined analyses across FFPE/FF and platforms using established batch correction methods as required to increase cohort sizes. However, some platforms appear to be better suited to FFPE samples, particularly archival material. CONCLUSIONS: Overall, we illustrate that technology selection is a balance between required resolution, sample quality, availability and cost.

HER2 regulates HIF-2α and drives an increased hypoxic response in breast cancer.

BACKGROUND: Tumour hypoxia is a driver of breast cancer progression associated with worse prognosis and more aggressive disease. The cellular response to hypoxia is mediated by the hypoxia-inducible transcription factors HIF-1 and HIF-2, whose transcriptional activity is canonically regulated through their oxygen-labile HIF-α subunits. These are constitutively degraded in the presence of oxygen; however, HIF-1α can be stabilised, even at high oxygen concentrations, through the activation of HER receptor signalling. Despite this, there is still limited understanding on how HER receptor signalling interacts with HIF activity to contribute to breast cancer progression in the context of tumour hypoxia. METHODS: 2D and 3D cell line models were used alongside microarray gene expression analysis and meta-analysis of publicly available gene expression datasets to assess the impact of HER2 overexpression on HIF-1α/HIF-2α regulation and to compare the global transcriptomic response to acute and chronic hypoxia in an isogenic cell line model of HER2 overexpression. RESULTS: HER2 overexpression in MCF7 cells leads to an increase in HIF-2α but not HIF-1α expression in normoxia and an increased upregulation of HIF-2α in hypoxia. Global gene expression analysis showed that HER2 overexpression in these cells promotes an exaggerated transcriptional response to both short-term and long-term hypoxia, with increased expression of numerous hypoxia response genes. HIF-2α expression is frequently higher in HER2-overexpressing tumours and is associated with worse disease-specific survival in HER2-positive breast cancer patients. HER2-overexpressing cell lines demonstrate an increased sensitivity to targeted HIF-2α inhibition through either siRNA or the use of a small molecule inhibitor of HIF-2α translation. CONCLUSIONS: This study suggests an important interplay between HER2 expression and HIF-2α in breast cancer and highlights the potential for HER2 to drive the expression of numerous hypoxia response genes in normoxia and hypoxia. Overall, these findings show the importance of understanding the regulation of HIF activity in a variety of breast cancer subtypes and points to the potential of targeting HIF-2α as a therapy for HER2-positive breast cancer.

On-treatment biomarkers can improve prediction of response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Neoadjuvant chemotherapy is increasingly given preoperatively to shrink breast tumours prior to surgery. This approach also provides the opportunity to study the molecular changes associated with treatment and evaluate whether on-treatment sequential samples can improve response and outcome predictions over diagnostic or excision samples alone. METHODS: This study included a total of 97 samples from a cohort of 50 women (aged 29-76, with 46% ER+ and 20% HER2+ tumours) with primary operable breast cancer who had been treated with neoadjuvant chemotherapy. Biopsies were taken at diagnosis, at 2 weeks on-treatment, mid-chemotherapy, and at resection. Fresh frozen samples were sequenced with Ion AmpliSeq Transcriptome yielding expression values for 12,635 genes. Differential expression analysis was performed across 16 patients with a complete pathological response (pCR) and 34 non-pCR patients, and over treatment time to identify significantly differentially expressed genes, pathways, and markers indicative of response status. Prediction accuracy was compared with estimations of established gene signatures, for this dataset and validated using data from the I-SPY 1 Trial. RESULTS: Although changes upon treatment are largely similar between the two cohorts, very few genes were found to be consistently different between responders and non-responders, making the prediction of response difficult. AAGAB was identified as a novel potential on-treatment biomarker for pathological complete response, with an accuracy of 100% in the NEO training dataset and 78% accuracy in the I-SPY 1 testing dataset. AAGAB levels on-treatment were also significantly predictive of outcome (p = 0.048, p = 0.0036) in both cohorts. This single gene on-treatment biomarker had greater predictive accuracy than established prognostic tests, Mammaprint and PAM50 risk of recurrence score, although interestingly, both of these latter tests performed better in the on-treatment rather than the accepted pre-treatment setting. CONCLUSION: Changes in gene expression measured in sequential samples from breast cancer patients receiving neoadjuvant chemotherapy resulted in the identification of a potentially novel on-treatment biomarker and suggest that established prognostic tests may have greater prediction accuracy on than before treatment. These results support the potential use and further evaluation of on-treatment testing in breast cancer to improve the accuracy of tumour response prediction.

Molecular changes during extended neoadjuvant letrozole treatment of breast cancer: distinguishing acquired resistance from dormant tumours.

BACKGROUND: The risk of recurrence for endocrine-treated breast cancer patients persists for many years or even decades following surgery and apparently successful adjuvant therapy. This period of dormancy and acquired resistance is inherently difficult to investigate; previous efforts have been limited to in-vitro or in-vivo approaches. In this study, sequential tumour samples from patients receiving extended neoadjuvant aromatase inhibitor therapy were characterised as a novel clinical model. METHODS: Consecutive tumour samples from 62 patients undergoing extended (4-45 months) neoadjuvant aromatase inhibitor therapy with letrozole were subjected to transcriptomic and proteomic analysis, representing before (≤ 0), early (13-120 days), and long-term (> 120 days) neoadjuvant aromatase inhibitor therapy with letrozole. Patients with at least a 40% initial reduction in tumour size by 4 months of treatment were included. Of these, 42 patients with no subsequent progression were classified as "dormant", and the remaining 20 patients as "acquired resistant". RESULTS: Changes in gene expression in dormant tumours begin early and become more pronounced at later time points. Therapy-induced changes in resistant tumours were common features of treatment, rather than being specific to the resistant phenotype. Comparative analysis of long-term treated dormant and resistant tumours highlighted changes in epigenetics pathways including DNA methylation and histone acetylation. The DNA methylation marks 5-methylcytosine and 5-hydroxymethylcytosine were significantly reduced in resistant tumours compared with dormant tissues after extended letrozole treatment. CONCLUSIONS: This is the first patient-matched gene expression study investigating long-term aromatase inhibitor-induced dormancy and acquired resistance in breast cancer. Dormant tumours continue to change during treatment whereas acquired resistant tumours more closely resemble their diagnostic samples. Global loss of DNA methylation was observed in resistant tumours under extended treatment. Epigenetic alterations may lead to escape from dormancy and drive acquired resistance in a subset of patients, supporting a potential role for therapy targeted at these epigenetic alterations in the management of resistance to oestrogen deprivation therapy.

Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer models.

BACKGROUND: The natural polyphenol myricetin induces cell cycle arrest and apoptosis in preclinical cancer models. We hypothesised that myricetin-derived flavonoids with enhanced redox properties, improved cell uptake and mitochondrial targeting might have increased potential as antitumour agents. METHODS: We studied the effect of a second-generation flavonoid analogue Oncamex in a panel of seven breast cancer cell lines, applying western blotting, gene expression analysis, fluorescence microscopy and immunohistochemistry of xenograft tissue to investigate its mechanism of action. RESULTS: Proliferation assays showed that Oncamex treatment for 8 h reduced cell viability and induced cytotoxicity and apoptosis, concomitant with increased caspase activation. Microarray analysis showed that Oncamex was associated with changes in the expression of genes controlling cell cycle and apoptosis. Fluorescence microscopy showed the compound's mitochondrial targeting and reactive oxygen species-modulating properties, inducing superoxide production at concentrations associated with antiproliferative effects. A preliminary in vivo study in mice implanted with the MDA-MB-231 breast cancer xenograft showed that Oncamex inhibited tumour growth, reducing tissue viability and Ki-67 proliferation, with no signs of untoward effects on the animals. CONCLUSIONS: Oncamex is a novel flavonoid capable of specific mitochondrial delivery and redox modulation. It has shown antitumour activity in preclinical models of breast cancer, supporting the potential of this prototypic candidate for its continued development as an anticancer agent.

Quantification of tumour budding, lymphatic vessel density and invasion through image analysis in colorectal cancer.

BACKGROUND: Tumour budding (TB), lymphatic vessel density (LVD) and lymphatic vessel invasion (LVI) have shown promise as prognostic factors in colorectal cancer (CRC) but reproducibility using conventional histopathology is challenging. We demonstrate image analysis methodology to quantify the histopathological features which could permit standardisation across institutes and aid risk stratification of Dukes B patients. METHODS: Multiplexed immunofluorescence of pan-cytokeratin, D2-40 and DAPI identified epithelium, lymphatic vessels and all nuclei respectively in tissue sections from 50 patients diagnosed with Dukes A (n = 13), Dukes B (n = 29) and Dukes C (n = 8) CRC. An image analysis algorithm was developed and performed, on digitised images of the CRC tissue sections, to quantify TB, LVD, and LVI at the invasive front. RESULTS: TB (HR =5.7; 95% CI, 2.38-13.8), LVD (HR =5.1; 95% CI, 2.04-12.99) and LVI (HR =9.9; 95% CI, 3.57-27.98) were successfully quantified through image analysis and all were shown to be significantly associated with poor survival, in univariate analyses. LVI (HR =6.08; 95% CI, 1.17-31.41) is an independent prognostic factor within the study and was correlated to both TB (Pearson r =0.71, p <0.0003) and LVD (Pearson r =0.69, p <0.0003). CONCLUSION: We demonstrate methodology through image analysis which can standardise the quantification of TB, LVD and LVI from a single tissue section while decreasing observer variability. We suggest this technology is capable of stratifying a high risk Dukes B CRC subpopulation and we show the three histopathological features to be of prognostic significance.

Basal-epithelial subpopulations underlie and predict chemotherapy resistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by extensive intratumoral heterogeneity, high metastasis, and chemoresistance, leading to poor clinical outcomes. Despite progress, the mechanistic basis of these aggressive behaviors remains poorly understood. Using single-cell and spatial transcriptome analysis, here we discovered basal epithelial subpopulations located within the stroma that exhibit chemoresistance characteristics. The subpopulations are defined by distinct signature genes that show a frequent gain in copy number and exhibit an activated epithelial-to-mesenchymal transition program. A subset of these genes can accurately predict chemotherapy response and are associated with poor prognosis. Interestingly, among these genes, elevated ITGB1 participates in enhancing intercellular signaling while ACTN1 confers a survival advantage to foster chemoresistance. Furthermore, by subjecting the transcriptional signatures to drug repurposing analysis, we find that chemoresistant tumors may benefit from distinct inhibitors in treatment-naive versus post-NAC patients. These findings shed light on the mechanistic basis of chemoresistance while providing the best-in-class biomarker to predict chemotherapy response and alternate therapeutic avenues for improved management of TNBC patients resistant to chemotherapy.

Neoadjuvant endocrine therapy in postmenopausal women with HR+/HER2- breast cancer.

INTRODUCTION: While endocrine therapy is the standard-of-care adjuvant treatment for hormone receptor-positive (HR+) breast cancers, there is also extensive evidence for the role of pre-operative (or neoadjuvant) endocrine therapy (NET) in HR+ postmenopausal women. AREAS COVERED: We conducted a thorough review of the published literature, to summarize the evidence to date, including studies of how NET compares to neoadjuvant chemotherapy, which NET agents are preferable, and the optimal duration of NET. We describe the importance of on-treatment assessment of response, the different predictors available (including Ki67, PEPI score, and molecular signatures) and the research opportunities the pre-operative setting offers. We also summarize recent combination trials and discuss how the COVID-19 pandemic led to increases in NET use for safe management of cases with deferred surgery and adjuvant treatments. EXPERT OPINION: NET represents a safe and effective tool for the management of postmenopausal women with HR+/HER2- breast cancer, enabling disease downstaging and a wider range of surgical options. Aromatase inhibitors are the preferred NET, with evidence suggesting that longer regimens might yield optimal results. However, NET remains currently underutilised in many territories and institutions. Further validation of predictors for treatment response and benefit is needed to help standardise and fully exploit the potential of NET in the clinic.

The Role of Nodes and Nodal Assessment in Diagnosis, Treatment and Prediction in ER+, Node-Positive Breast Cancer.

The majority of breast cancers are oestrogen receptor-positive (ER+). In ER+ cancers, oestrogen acts as a disease driver, so these tumours are likely to be susceptible to endocrine therapy (ET). ET works by blocking the hormone's synthesis or effect. A significant number of patients diagnosed with breast cancer will have the spread of tumour cells into regional lymph nodes either at the time of diagnosis, or as a recurrence some years later. Patients with node-positive disease have a poorer prognosis and can respond less well to ET. The nodal metastases may be genomically similar or, as is becoming more evident, may differ from the primary tumour. However, nodal metastatic disease is often not assessed, and treatment decisions are almost always based on biomarkers evaluated in the primary tumour. This review will summarise the evidence in the field on ER+, node-positive breast cancer, including diagnosis, treatment, prognosis and predictive tools.

Mondor's disease of the breast: A cutaneous thromboembolic manifestation of Covid-19?

BACKGROUND: Mondor's disease is a rare disorder characterised by thrombosis of superficial veins within the subcutaneous tissue of the breast and other organs. While factors such as trauma, infection, physical exertion, breast cancer and breast surgery have been implicated, in the majority no cause is identified. PATIENTS: Twenty patients presented with a clinical diagnosis of Mondor's disease to the Edinburgh Breast Services in 2020. We present the etiopathogenic data as well as clinical and imaging diagnostic findings. RESULTS: During 2020, the annual incidence of Mondor's disease, in the UK's largest breast unit, increased five-fold compared to data from the previous year. This variation in the frequency of cases corresponded to trends in the frequency of Covid-19 infection during the pandemic. None of the patients had diagnosed COVID and few had any known etiopathogenic causes for their Mondor's. CONCLUSION: Several recent studies have provided evidence for links between Covid-19 and thromboembolic events. Isolated reports have proposed a link between Covid-19 and Mondor's disease of the penis. Here we present data on a large series of Mondor's disease of the breast supporting a link between breast Mondor's and Covid-19.

Characterisation of the Stromal Microenvironment in Lobular Breast Cancer.

Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of ILC. We used laser-capture microdissection to separate tumor epithelium from stroma in 23 ER+ ILC primary tumors. Gene expression analysis identified 45 genes involved in regulation of the extracellular matrix (ECM) that were enriched in the non-immune stroma of ILC, but not in non-immune stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets, with PAPPA and TIMP2 being associated with better survival in ILC but not IDC. PAPPA, a gene involved in IGF-1 signaling, was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. Analysis of PAPPA- and IGF1-associated genes identified a paracrine signaling pathway, and active PAPP-A was shown to be secreted from primary CAFs. This is the first study to demonstrate molecular differences in the TME between ILC and IDC identifying differences in matrix organization and growth factor signaling pathways.

The IL6-like Cytokine Family: Role and Biomarker Potential in Breast Cancer.

IL6-like cytokines are a family of regulators with a complex, pleiotropic role in both the healthy organism, where they regulate immunity and homeostasis, and in different diseases, including cancer. Here we summarise how these cytokines exert their effect through the shared signal transducer IL6ST (gp130) and we review the extensive evidence on the role that different members of this family play in breast cancer. Additionally, we discuss how the different cytokines, their related receptors and downstream effectors, as well as specific polymorphisms in these molecules, can serve as predictive or prognostic biomarkers with the potential for clinical application in breast cancer. Lastly, we also discuss how our increasing understanding of this complex signalling axis presents promising opportunities for the development or repurposing of therapeutic strategies against cancer and, specifically, breast neoplasms.

Tissue- and Liquid-Based Biomarkers in Prostate Cancer Precision Medicine.

Worldwide, prostate cancer (PC) is the second-most-frequently diagnosed male cancer and the fifth-most-common cause of all cancer-related deaths. Suspicion of PC in a patient is largely based upon clinical signs and the use of prostate-specific antigen (PSA) levels. Although PSA levels have been criticised for a lack of specificity, leading to PC over-diagnosis, it is still the most commonly used biomarker in PC management. Unfortunately, PC is extremely heterogeneous, and it can be difficult to stratify patients whose tumours are unlikely to progress from those that are aggressive and require treatment intensification. Although PC-specific biomarker research has previously focused on disease diagnosis, there is an unmet clinical need for novel prognostic, predictive and treatment response biomarkers that can be used to provide a precision medicine approach to PC management. In particular, the identification of biomarkers at the time of screening/diagnosis that can provide an indication of disease aggressiveness is perhaps the greatest current unmet clinical need in PC management. Largely through advances in genomic and proteomic techniques, exciting pre-clinical and clinical research is continuing to identify potential tissue, blood and urine-based PC-specific biomarkers that may in the future supplement or replace current standard practices. In this review, we describe how PC-specific biomarker research is progressing, including the evolution of PSA-based tests and those novel assays that have gained clinical approval. We also describe alternative diagnostic biomarkers to PSA, in addition to biomarkers that can predict PC aggressiveness and biomarkers that can predict response to certain therapies. We believe that novel biomarker research has the potential to make significant improvements to the clinical management of this disease in the near future.

Corrigendum: Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines.

[This corrects the article DOI: 10.3389/fvets.2020.00439.].

The Signal Transducer IL6ST (gp130) as a Predictive and Prognostic Biomarker in Breast Cancer.

Novel biomarkers are needed to continue to improve breast cancer clinical management and outcome. IL6-like cytokines, whose pleiotropic functions include roles in many hallmarks of malignancy, rely on the signal transducer IL6ST (gp130) for all their signalling. To date, 10 separate independent studies based on the analysis of clinical breast cancer samples have identified IL6ST as a predictor. Consistent findings suggest that IL6ST is a positive prognostic factor and is associated with ER status. Interestingly, these studies include 4 multigene signatures (EndoPredict, EER4, IRSN-23 and 42GC) that incorporate IL6ST to predict risk of recurrence or outcome from endocrine or chemotherapy. Here we review the existing evidence on the promising predictive and prognostic value of IL6ST. We also discuss how this potential could be further translated into clinical practice beyond the EndoPredict tool, which is already available in the clinic. The most promising route to further exploit IL6ST's promising predicting power will likely be through additional hybrid multifactor signatures that allow for more robust stratification of ER+ breast tumours into discrete groups with distinct outcomes, thus enabling greater refinement of the treatment-selection process.

A Novel Approach for the Discovery of Biomarkers of Radiotherapy Response in Breast Cancer.

Radiotherapy (RT) is an important treatment modality for the local control of breast cancer (BC). Unfortunately, not all patients that receive RT will obtain a therapeutic benefit, as cancer cells that either possess intrinsic radioresistance or develop resistance during treatment can reduce its efficacy. For RT treatment regimens to become personalised, there is a need to identify biomarkers that can predict and/or monitor a tumour's response to radiation. Here we describe a novel method to identify such biomarkers. Liquid chromatography-mass spectrometry (LC-MS) was used on conditioned media (CM) samples from a radiosensitive oestrogen receptor positive (ER+) BC cell line (MCF-7) to identify cancer-secreted biomarkers which reflected a response to radiation. A total of 33 radiation-induced secreted proteins that had higher (up to 12-fold) secretion levels at 24 h post-2 Gy radiation were identified. Secretomic results were combined with whole-transcriptome gene expression experiments, using both radiosensitive and radioresistant cells, to identify a signature related to intrinsic radiosensitivity. Gene expression analysis assessing the levels of the 33 proteins showed that 5 (YBX3, EIF4EBP2, DKK1, GNPNAT1 and TK1) had higher expression levels in the radiosensitive cells compared to their radioresistant derivatives; 3 of these proteins (DKK1, GNPNAT1 and TK1) underwent in-lab and initial clinical validation. Western blot analysis using CM samples from cell lines confirmed a significant increase in the release of each candidate biomarker from radiosensitive cells 24 h after treatment with a 2 Gy dose of radiation; no significant increase in secretion was observed in the radioresistant cells after radiation. Immunohistochemistry showed that higher intracellular protein levels of the biomarkers were associated with greater radiosensitivity. Intracellular levels were further assessed in pre-treatment biopsy tissues from patients diagnosed with ER+ BC that were subsequently treated with breast-conserving surgery and RT. High DKK1 and GNPNAT1 intracellular levels were associated with significantly increased recurrence-free survival times, indicating that these two candidate biomarkers have the potential to predict sensitivity to RT. We suggest that the methods highlighted in this study could be utilised for the identification of biomarkers that may have a potential clinical role in personalising and optimising RT dosing regimens, whilst limiting the administration of RT to patients who are unlikely to benefit.

The Importance of the Tumor Microenvironment and Hypoxia in Delivering a Precision Medicine Approach to Veterinary Oncology.

Treating individual patients on the basis of specific factors, such as biomarkers, molecular signatures, phenotypes, environment, and lifestyle is what differentiates the precision medicine initiative from standard treatment regimens. Although precision medicine can be applied to almost any branch of medicine, it is perhaps most easily applied to the field of oncology. Cancer is a heterogeneous disease, meaning that even though patients may be histologically diagnosed with the same cancer type, their tumors may have different molecular characteristics, genetic mutations or tumor microenvironments that can influence prognosis or treatment response. In this review, we describe what methods are currently available to clinicians that allow them to monitor key tumor microenvironmental parameters in a way that could be used to achieve precision medicine for cancer patients. We further describe exciting novel research involving the use of implantable medical devices for precision medicine, including those developed for mapping tumor microenvironment parameters (e.g., O2, pH, and cancer biomarkers), delivering local drug treatments, assessing treatment responses, and monitoring for recurrence and metastasis. Although these research studies have predominantly focused on and were tailored to humans, the results and concepts are equally applicable to veterinary patients. While veterinary clinical studies that have adopted a precision medicine approach are still in their infancy, there have been some exciting success stories. These have included the development of a receptor tyrosine kinase inhibitor for canine mast cell tumors and the production of a PCR assay to monitor the chemotherapeutic response of canine high-grade B-cell lymphomas. Although precision medicine is an exciting area of research, it currently has failed to gain significant translation into human and veterinary healthcare practices. In order to begin to address this issue, there is increasing awareness that cross-disciplinary approaches involving human and veterinary clinicians, engineers and chemists may be needed to help advance precision medicine toward its full integration into human and veterinary clinical practices.