Primary Outcomes

Description: The changes of oxysterols content in serum/plasma after 8 weeks of phytosterols intervention compared to placebo. After the dietary intervention, we expect to observe a change of -20% in circulating 27-hydroxycholesterol content (marker of oxysterols systemic levels). Concentration of oxysterols using LC-MS/MS measurement of plasma in 50 subjects after placebo and after intervention.

Measure: To change circulating oxysterols levels after phytosterols intervention.

Time: Serum/plasma oxysterols concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Secondary Outcomes

Description: Concentration of oxysterols using LC-MS/MS measurement of host cells in 50 subjects after placebo and after intervention. Effect of phytosterols enriched foods consumption compared to placebo intervention on migratory and chemoresistance properties of breast cancer cell lines (MDA.MB.231, MDA.MB.468, MCF7 and T47D) when in co-culture with the host-cells collected in each step of the trial.

Measure: Change intra-cellular adipocyte and macrophages oxysterols concentrations

Time: Serum/plasma/medium oxysterols concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Effect of phytosterols enriched foods consumption compared to placebo intervention on migratory and chemoresistance properties of breast cancer cell lines (MDA.MB.231, MDA.MB.468, MCF7 and T47D) when in co-culture with the host-cells collected in each step of the trial. Changes in proteins expression of oxysterols target genes.

Measure: Study of adipocytes and macrophages interaction with breast cancer cell lines

Time: Protein expression will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Effect of phytosterols enriched foods consumption compared to placebo intervention on migratory and chemoresistance properties of breast cancer cell lines (MDA.MB.231, MDA.MB.468, MCF7 and T47D) when in co-culture with the host-cells collected in each step of the trial. Changes in gene expression of oxysterols target genes.

Measure: Study of adipocytes and macrophages interaction with breast cancer cell lines

Time: Gene expression will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Study of the effect of phytosterols on LDL-C concentration in 50 subjects after placebo and after intervention using Alere Afinion™.

Measure: Study the effect of phytosterols on LDL-C

Time: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Study of the effect of phytosterols on HDL-C concentration in 50 subjects after placebo and after intervention using Alere Afinion™.

Measure: Study the effect of phytosterols on HDL-C

Time: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Study of the effect of phytosterols on Total Cholesterol concentration in 50 subjects after placebo and after intervention using Alere Afinion™.

Measure: Study the effect of phytosterols on Total Cholesterol

Time: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Study of the effect of phytosterols on Triglycerides concentration in 50 subjects after placebo and after intervention using Alere Afinion™.

Measure: Study the effect of phytosterols on Triglycerides

Time: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Study of the effect of phytosterols on non-HDL-C concentration in 50 subjects after placebo and after intervention using Alere Afinion™.

Measure: Study the effect of phytosterols on non-HDL-C

Time: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Phytosterols panel serum/plasma levels after phytosterols enriched food or placebo intervention during all the steps of the trial.

Measure: Quantify phytosterols in blood samples from volunteers.

Time: Serum/plasma phytosterols and lipid concentrations will be measured during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Other Outcomes

Description: RNA sequence will be measured with RNA-seq techniques before and after phytosterols intervention to identify the molecular effectors of the paracrine regulatory systems in the oxysterols, LDL-C and secondary BCa pattern.

Measure: Study RNA sequences changes in the oxysterols/LDL-C pathway and secondary breast cancer before and after phytosterols intervention .

Time: RNA will be studied during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Description: Changes in interactions between proteins and DNA and using Chip/seq will be measured before and after phytosterols intervention to identify the molecular effectors of the paracrine regulatory systems in the oxysterols, LDL-C and secondary BCa pattern.

Measure: Study changes in the interactions between proteins and DNA in the oxysterols/LDL-C pathway and secondary breast cancer before and after phytosterols intervention .

Time: interactions between proteins and DNA will be studied during all the steps of the trial (baseline, 8th week, 12nd week, 20th week)

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Primary Outcomes

Description: Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery, evaluating if there is a decrease in the proliferating index (Ki-67 expression by immunohistochemistry). Positive response: differences higher than 30%.

Measure: Measurable decrease in tumor cell proliferation from baseline to time of surgery

Time: Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

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Secondary Outcomes

Description: Treatment efficacy will be assessed by comparing tissue samples from the baseline biopsy and tissue samples collected from the day of surgery, evaluating if there is an increase in apoptotic cells measuring TUNNEL and caspase 3 expression. Positive response: difference higher than 30%.

Measure: Measurable increases in apoptotic markers from baseline to time of surgery

Time: Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

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Description: MFP action will be measured evaluating the expression of downstream markers related to PR activation such as CCND1, MYC, pSTAT5 and other proteins by immunohistochemistry. Positive response: differences higher than 30%

Measure: Measurable changes in signaling pathways downstream PR

Time: Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

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Other Outcomes

Description: Measured by ecographic imaging. Twenty per cent of decrease in overall tumor size will be considered as a significant change.

Measure: Changes in tumor size

Time: Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

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Description: Differences in gene expression between biopsy core and surgery sample higher than 20 % will be considered as an effective drug response.

Measure: RNAseq analysis of gene expression

Time: Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

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Description: Levels of Mifepristone will be measured by HPLC in the blood sample after treatment and correlate these levels with response to treatment (outcome 1).

Measure: Measure serum Mifepristone levels after 14 days Mifepristone treatment

Time: Baseline to time of surgery (14 days of treatment between biopsy core and surgery)

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Primary Outcomes

Description: To evaluate Ki67 changes. The Ki-67 protein is a cellular marker for proliferation. It is strictly associated with cell proliferation. Ki67 has been shown to be a surrogate marker of biological activity and treatment response in estrogen receptor positive breast cancer treated with endocrine therapy.

Measure: Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design

Time: after 10-28 days of single agent lenvatinib

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Description: To evaluate histological response such as the improvement in the appearance of microscopic tissue specimens after treatment with lenvatinib. The improved appearance of biopsy specimens after treatment often suggests the patient's prognosis will improve as well.

Measure: Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design

Time: after 10-28 days of single agent lenvatinib

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Description: To evaluate apoptosis. Apoptosis is the death of cells which occurs as a normal and controlled part of an organism's growth or development. The presence of apoptosis indicates anti-cancer effects.

Measure: Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design

Time: after 10-28 days of single agent lenvatinib

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Description: To evaluate RET. RET is an estrogen response gene. RET is associated with resistance to tamoxifen and aromatase inhibitors, and increased RET expression has been demonstrated in hormone resistant cell lines and primary tumors.

Measure: Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design

Time: after 10-28 days of single agent lenvatinib

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Description: To evaluate downstream targets such as AKT. AKT /protein kinase B (PKB) is a cardinal node in diverse signaling cascades important in both normal cellular physiology and various disease states. AKT signaling regulates cell proliferation and survival, cell growth (size), glucose metabolism, cell motility and angiogenesis. Aberrant regulation of these processes results in cellular perturbations considered hallmarks of cancer, and numerous studies testify to the frequent hyperactivation of AKT signaling in many human cancer.

Measure: Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design

Time: after 10-28 days of single agent lenvatinib

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Description: To evaluate downstream targets such as ERK. ERK is Extracellular signal-regulated kinase. Deregulation of ERK signalling pathway is linked to many other aspects of the tumour phenotype.

Measure: Biological effects of short-course single agent lenvatinib in estrogen receptor positive breast cancer using a window-of-opportunity design

Time: after 10-28 days of single agent lenvatinib

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Secondary Outcomes

Description: to obtain the percentage change in primary breast tumor dimension measured by ultrasound

Measure: Changes in the primary tumor dimensions

Time: after 10-28 days of single agent lenvatinib

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Description: to obtain the proportion of subjects with tumor reduction of at least 10%

Measure: The proportion of subjects with tumor reduction

Time: after 10-28 days of single agent lenvatinib

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Description: To compare clinical response of lenvatinib in RET negative versus RET positive, ER positive breast cancers

Measure: Comparison of the clinical response of lenvatinib in RET negative versus RET positive, ER positive breast cancers

Time: after 10-28 days of single agent lenvatinib

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Description: : Comparison of the number of patients with Ki67 changes, histological response, apoptosis, RET and downstream targets such as AKT and ERK, between RET negative versus RET positive, ER positive breast cancers.

Measure: Comparison in the overall average changes in biological effects of lenvatinib between RET negative and RET positive, ER positive breast cancers.

Time: after 10-28 days of single agent lenvatinib

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