Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

Diana, Anna; Carlino, Francesca; Franzese, E.; Oikonomidou, Olga; Criscitiello, Carmen; Vita, Ferdinando De; Ciardiello, Fortunato; Orditura, Michele

doi:10.3390/cancers12040819

Cited by 70 publications

(55 citation statements)

References 122 publications

(132 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most relevant recent clinical trials about NAC treatment with pCR as endpoint are described in Table 1 . Specific recent reviews on clinical trials evaluating NAC in TN and HER2+ BC give a good account of them [ 17 , 18 ].…”

Section: Neoadjuvant Chemotherapy In Breast Cancer Treatmentsmentioning

confidence: 99%

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Chica-Parrado

Godoy-Ortiz

Jiménez

et al. 2020

Cancers

View full text Add to dashboard Cite

Neoadjuvant Chemotherapy (NAC) in Breast Cancer (BC) has proved useful for the reduction in tumor burden prior to surgery, allowing for a more extensive breast preservation and the eradication of subjacent micrometastases. However, the impact on prognosis is highly dependent on the establishment of Pathological Complete Response (pCR), in particular for Triple Negative (TN) and Hormonal Receptor negative/Human Epidermal growth factor Receptor 2 positive (HR−/HER2+) subtypes. Several pCR predictors, such as PAM50, Integrative Cluster (IntClust), mutations in PI3KCA, or the Trastuzumab Risk model (TRAR), are useful molecular tools for estimating response to treatment and are prognostic. Major evolution events during BC NAC that feature the Residual Disease (RD) are the loss of HR and HER2, which are prognostic of bad outcome, and stemness and immune depletion-related gene expression aberrations. This dynamic nature of the determinants of response to BC NAC, together with the extensive heterogeneity of BC, raises the need to discern the individual and subtype-specific determinants of resistance. Moreover, refining the current approaches for a comprehensive monitoring of tumor evolution during treatment, RD, and eventual recurrences is essential for identifying new actionable alterations and the integral best management of the disease.

show abstract

Section: Neoadjuvant Chemotherapy In Breast Cancer Treatmentsmentioning

confidence: 99%

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Chica-Parrado

Godoy-Ortiz

Jiménez

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Intrinsic genomic and molecular differences between different breast cancer subtypes explain their distinct clinical course and general differences in their drug sensitivities [ 17 , 18 , 19 ]. The breast cancer subtype with the least therapeutic options and therefore the poorest outcome is triple-negative breast cancer (TNBC) [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells

Marczyk

Patwardhan

Zhao

et al. 2020

Cancers

View full text Add to dashboard Cite

Cancer cells employ various defense mechanisms against drug-induced cell death. Investigating multi-omics landscapes of cancer cells before and after treatment can reveal resistance mechanisms and inform new therapeutic strategies. We assessed the effects of navitoclax, a BCL2 family inhibitor, on the transcriptome, methylome, chromatin structure, and copy number variations of MDA-MB-231 triple-negative breast cancer (TNBC) cells. Cells were sampled before treatment, at 72 h of exposure, and after 10-day drug-free recovery from treatment. We observed transient alterations in the expression of stress response genes that were accompanied by corresponding changes in chromatin accessibility. Most of these changes returned to baseline after the recovery period. We also detected lasting alterations in methylation states and genome structure that suggest permanent changes in cell population composition. Using single-cell analyses, we identified 2350 genes significantly upregulated in navitoclax-resistant cells and derived an 18-gene navitoclax resistance signature. We assessed the navitoclax-response-predictive function of this signature in four additional TNBC cell lines in vitro and in silico in 619 cell lines treated with 251 different drugs. We observed a drug-specific predictive value in both experiments, suggesting that this signature could help guiding clinical biomarker studies involving navitoclax.

show abstract

“…Overall, it has been hypothesized that the modulation of the immune system is a candidate for the development of more effective therapies in breast cancer. However, breast cancer is a heterogeneous disease, with HER2 + and TNBC being more immunogenic compared to hormone receptor (HR)-positive subtypes ( 90 – 92 ). HER2 + and TNBC are more likely to be infiltrated by tumor-infiltrating lymphocytes (TILs) and to express programmed death ligand-1 (PD-L1) in the TME than ER- or PR-expressing luminal tumors ( 93 – 95 ).…”

Section: Discussionmentioning

confidence: 99%

Physical Activity and Breast Cancer Prevention: Possible Role of Immune Mediators

Rogers

2020

Front. Nutr.

View full text Add to dashboard Cite

There is strong evidence that physical activity (PA) reduces risk, recurrence, and mortality from breast cancer. Emerging data suggest that PA induces changes in inflammatory and immune mediators that may contribute to beneficial effects on breast cancer outcomes. Thus, the goal of this review was to evaluate the evidence linking the protective benefit of PA to modulation of immune responses in breast cancer. A literature search was conducted to identify studies that evaluated the impact of PA on tumor and immune outcomes in breast cancer patients and in mammary tumor models. Nineteen studies investigated the effect of PA interventions on cancer immune outcomes using preclinical breast cancer models. Tumor growth was reduced in 11 studies, unchanged in three studies, and increased in one study. Spontaneous metastasis was reduced in two studies and survival was improved in four studies. Frequently assessed immune outcomes include splenic cell number and function, circulating inflammatory cytokines, and intratumoral immune cells and inflammatory markers. Circulating inflammatory cytokine responses were heterogeneous in preclinical models. Within the tumor microenvironment (TME), several studies documented a change in the infiltration of immune cells with an increase in effector cells and a reduction in immune suppressive cells. Twenty-three studies investigated the effect of PA interventions on immune outcomes in breast cancer patients. Thirteen studies used aerobic PA interventions and 10 studies used a combination of aerobic and resistance exercise interventions. Cycling and treadmill activities were the most commonly used PA modalities. Circulating immune cells and inflammatory cytokines were the most frequently assessed immune outcomes in the clinical studies. Among the 19 studies that evaluated a PA intervention during the post treatment period, 10 reported a reduction in the levels of at least one inflammatory cytokine. No inflammatory cytokines were quantified in the three studies that evaluated a PA intervention during treatment with chemotherapy. Immune outcomes within the tumor were assessed in only one study performing a PA intervention prior to surgery. Results from preclinical and clinical studies suggest that PA exerts heterogeneous effects on inflammatory cytokines, but may alter the gene expression profile and immune infiltrates in the tumor which may result in a reduction in immunosuppressive factors. However, additional studies are needed to better understand the effect of PA on immune outcomes in the TME.

show abstract

Early Triple Negative Breast Cancer: Conventional Treatment and Emerging Therapeutic Landscapes

Cited by 70 publications

References 122 publications

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Resistance to Neoadjuvant Treatment in Breast Cancer: Clinicopathological and Molecular Predictors

Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells

Physical Activity and Breast Cancer Prevention: Possible Role of Immune Mediators

Contact Info

Product

Resources

About