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Vitamin D And Estrogen Positive Breast Cancer

Second Harmonic Generation Microscopy

High Levels of Vitamin D Linked to Improved Breast Cancer Survival

SHG images of collagen fibers and two photon excitation fluorescence images of epithelial structures were obtained using a Leica TCS SP8 confocal microscope equipped with a tunable titanium-sapphire laser . Non-descanned low-noise Leica hybrid detectors collected light in the 460+/25nm and 525+/25nm ranges at an excitation wavelength of 920nm. In this study, we used a water-immersion 40x objective . Images with a size of 512×512 were acquired at an interval of 1 um along the z-axis. While efforts were made to only include one epithelial structure in a 3D stack, it was not always possible especially at the higher calcitriol doses given the contraction of the gels and the consequent crowding of the structures. Reconstruction of 3D images was performed using FIJI .

Vitamin D Through Sunlight Exposure And Diet

Findings from studies on vitamin D and decreased breast cancer risk are mixed.

Studying vitamin D with measures of sunlight exposure and diet has some challenges. Its hard to measure sunlight exposure. And, because so many foods that contain vitamin D also contain calcium, its hard to single out the effects of vitamin D alone.

Description Of Study Participants

Participants were sampled from a prospective cohort study, the Sister Study, which included 50,884 women who had never had breast cancer when they enrolled. To be eligible, women had to have at least 1 sister previously diagnosed with breast cancer, be aged 3574 years, and live in the United States. During enrollment , participants completed a computer-assisted telephone interview, providing data on demographic characteristics, reproductive history, personal and familial health histories, and other topics. Trained medical examiners collected biospecimens and took body measurements, and all participants provided written informed consent. The study was approved and overseen by the institutional review boards of the National Institute of Environmental Health Sciences and the Copernicus Group.

Sister Study participants are recontacted annually for updates on their health. More detailed questionnaires are completed every 23 years. Women with incident cancer are asked to provide a copy of the pathology report and to authorize release of their medical records. All analyses conducted here were based on data collected through September 2016 .

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Breast Cancer : Much Progress But Work Remains

Mention that statistic, and many women in the U.S. immediately know it refers to their lifetime risk of getting breast cancer.

Although the statistic may stir up anxiety, those diagnosed with breast cancer today have a more positive prognosis than ever, experts say. Thats due to better understanding of the disease, wider choices of treatments, and more individualized treatment designed to reduce the risk of recurrence and lessen side effects.

While breast cancer incidence has risen by 0.5% per year in recent years, and it remains the second leading cause of cancer death in women, outpaced only by lung cancer, there are now more than 3.8 million breast cancer survivors in the U.S.

If the disease is caught early, women with breast cancer have a survival rate of an astounding 99%, though that may dip to 28% if the cancer has spread.

But despite the progress, much work remains. Read on to see how far weve come in the fight against breast cancer and what experts say needs to happen next.

Breast Cancer: Not a Single Disease

Breast cancer is increasingly viewed as multiple different diseases, says Harold J. Burstein, MD, a breast oncologist at the Dana-Farber Cancer Institute in Boston.

That discovery, in turn, has helped to individualize treatment and predict exactly how much treatment is needed for a specific patient, he and other experts say.

Molecular Diagnostics and ER-Positive Cancers

New Hope for HER2-Positive Cancers

Expanded Genetic Testing

Which Breast Cancer Is Fed By Estrogen

Progesterone and Breast Cancer

Asked by: Nicholaus Beahan

In ER-positive breast cancer, cancerous cells receive their growth signals from the hormone estrogen. Estrogen receptors are the most common type of hormone receptor on breast cells. For this reason, ER-positive breast cancer is more common than other types of breast cancer.

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What Types Of Breast Cancer Have The Highest Recurrence Rates

A study published in the Journal of Clinical Oncology found the risk of recurrence for all breast cancers was highest in the first five years from the initial cancer diagnosis at 10.4%. This was highest between the first and second years after the initial diagnosis. During the first five years after the initial diagnosis, patients with oestrogen receptor positive breast cancer had lower rates of recurrence compared with those with ER negative disease. However, beyond five years, patients with ER positive disease had higher rates of recurrence.

Actions Of Vdr Agonists On Breast Cancer Cells And Tumors

Animal models of established breast cancer have demonstrated that VDR agonists can reduce tumor growth with minimal effects on calcemia . In experimental metastasis paradigms, the vitamin D analog EB1089 inhibited secondary tumors, blocked skeletal metastases and improved survival . More recently, dietary modifications have been shown to alter breast tumor growth and progression. Increasing dietary vitamin D3 from 1000 IU/kg diet to 5000 IU/kg diet significantly reduced growth of established MCF-7 xenografts, with equivalent potency to 1,252D3 . In another study, vitamin D deficiency sufficient to enhance bone turnover promoted the skeletal growth of breast cancer metastases . For further details on these and other in vivo studies, several recent comprehensive reviews on vitamin D and breast cancer are available .

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Vitamin D Levels Versus Breast Cancer Prognostic Parameters

An equal number of premenopausal and postmenopausal women were in the two groups. No significant difference was observed between serum 25-OH vitamin D levels in postmenopausal women and premenopausal women . Women who did not fall into the clear-cut category of premenopausal or postmenopausal were classified into the perimenopausal group, and seven of such women were not included in the analysis. No patients presented in stages I and IV. The clinical stage of a tumor did not bear any statistically significant relationship with the serum 25-OH vitamin D levels in this study. A statistically significant association was observed between serum 25-OH vitamin D levels and histological grades of breast cancer. Patients with poorly differentiated breast cancer had lower 25-OH vitamin D levels than patients with moderately and well-differentiated tumors .

Vitamin D Pathway Expression In Established Breast Cancer

What Is the Role of Vitamin D in Breast Cancer Treatment?

Table 1. Frequency of genomic alterations in VDR and CYP24A1 derived from The Cancer Genome Atlas dataset of human breast tumors.

Despite these data, in vitro studies have demonstrated that specific oncogenes can deregulate VDR expression. For instance, comparison of VDR expression in a series of isogenic, progressively transformed human mammary epithelial cell lines indicated that VDR expression and function was reduced more than 70% in HME cells expressing SV40 and/or RAS compared to the non-transformed HME cells from which they were derived . Likewise, SV40 and RAS have been shown to reduce VDR activity in other breast cancer cell model systems . Transcriptional repressors linked to the epithelial mesenchymal transition such as SNAIL and SLUG have also been shown to down-regulate VDR . Thus, it is clear that there are distinct mechanisms targeting both the VDR gene itself and its protein product. Data on receptor expression derived from whole tumors may be somewhat misleading since cancer progression is driven by genetic instability and outgrowth of cells with advantageous mutations, such as activation of oncogenes. These studies indicate that abrogated expression and/or function of VDR may be limited to certain subsets of cells within individual tumors that have sustained specific molecular genetic alterations.

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Regulation Of Proliferation Apoptosis Invasion And Metastasis

Calcitriol inhibits the growth of both ER+ and ER-negative human BCa cell lines ]. In general ER+ BCa cell lines appear to be more sensitive to the growth inhibitory effects of calcitriol than the ER-negative cell lines . In most BCa cells calcitriol induces cell cycle arrest by increasing the expression of cyclin-dependent kinase inhibitors and decreasing cyclin-dependent kinase activity . In some cells calcitriol promotes apoptosis by modulating the expression of the bcl-2 family of genes and in other BCa cells potentiates the induction of apoptosis through the death receptor pathway . Calcitriol and its analogs also inhibit the growth of BCa cells by regulating the expression of oncogenes such as c-myc and c-fos and modulating the actions of the genes that encode several growth factors including epidermal growth factor , transforming growth factor and insulin-like growth factor-I ]. Further, calcitriol and its analogs induce a more differentiated phenotype in some BCa cells reversing the myoepithelial features associated with more aggressive forms of BCa .

Phytoestrogens And Soy: The Debate

Phytoestrogens are compounds that have a mild estrogenic effect and are found in whole grains, nuts and seeds, and many other botanicals, fruits and vegetables. These foods are associated with a reduced risk of breast cancer as well as reduced cancer reoccurrence.

The controversy becomes heated in the debate over soy-containing foods. This issue is complex, with some studies showing that eating soy early in life can reduce breast cancer risk. On the other hand, the consumption of concentrated soy extracts showed increased proliferation of breast cancer cells. Finally, other studies show a protective or neutral effect from whole soy foods.

My recommendation for soy is to eat whole soy foods in moderation no more than several servings per week, preferably fermented soy foods such as miso or tempeh. Avoid soy protein isolates and supplements containing concentrated soy isoflavones.

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Vdr And Breast Cancer Mortality

The present study showed a statistically significant association between BCM and VDR tumor expression among breast cancer patients , which has not been reported previously. Previous studies have not used BCM as endpoint when evaluating breast cancer prognosis , and associations found between VDR expression and different endpoints are not conclusive. The most recent and largest study, by Al-Azhri et al., reported very similar results to ours as regards to covariation with tumor prognostic factors, but showed no association between VDR expression and overall survival, progression-free survival, or breast cancer-specific survival . Differences in study population such as a shorter follow-up time and differing tumor characteristics and that they might have included women with metastatic disease in their study population may explain some of these discrepancies. The earlier and smaller studies have used different approaches on retrieving information on VDR expression and have not associated VDR expression with any differences in survival although Berger et al. noted that VDR-positive tumors were associated with a longer disease-free interval . Ditsch et al. showed that VDR expression was associated with a between better progression-free survival, and overall survival in univariate analyses , which strengthens our results.

What Are Estrogen And Progesterone Receptors

How Vitamin D Stops Cancer Stem Cells

Estrogen and progesterone are two hormones that can help breast cancer grow. These hormones bind to estrogen and progesterone receptors.

Following a breast biopsy, a pathologist will perform a test called an immunohistochemical staining assay on the tissue sample. The test can detect the presence of estrogen and progesterone receptors.

Hormone receptor status provides a lot of information on how the cancer is likely to behave. Its also a key factor in determining the best possible treatment.

HR-positive breast cancer typically responds well to hormone therapy. These therapies block the production of the hormones or interfere with their effects on breast cancer cells. On the other hand, HR-negative breast cancers dont respond to hormone therapy, so other treatment options will be more effective.

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Dos And Donts For Estrogen

Breast cancer is not just one disease it comes in many variations.

One of the primary factors in determining the type of breast cancer is the sensitivity of the tumor cells to estrogen. If a breast tumor is hormone-sensitive or estrogen receptor-positive, it means there are specific estrogen receptors on the tumor cells, and when estrogen binds with these receptors, it transfers a message to the cancer cells. Like a lock and key effect, the breast tumor cells are stimulated by estrogen to grow and reproduce. Therefore, one of the main goals of therapy or intervention with hormone-positive cancer is to reduce hormonal stimulation as much as possible.

Minimize Exposure To Heavy Metals

Heavy metals including copper, cobalt, arsenic, cadmium, mercury and lead have been found to stimulate estrogen receptors. Sources of arsenic include some brands of rice, seafood, well water cadmium is high in cigarettes and can be found in some soils mercury is mainly prevalent in larger fish and old dental amalgams and lead contamination is a component of air pollution, paint and dyes, and ceramic glazes among other sources.

Essentially, heavy metal and toxin exposure is hard to completely avoid in our world, even with careful choices. Because of this, I advise my patients to use compounds that provide safe, gentle detoxification of heavy metals and other contaminants, on a daily or periodic basis.

Modified citrus pectin, is derived from the pith of citrus fruit and has been shown in human studies to remove harmful heavy metals and reduce toxic body burden over time. MCP is able to cross the intestinal barrier and circulate in the bloodstream, where it binds to toxins and heavy metals and helps safely excrete them, without removing essential minerals. I also recommend ingredients such alpha-lipoic acid, N-acetyl cysteine, garlic, cilantro and other herbs and nutrients that provide support for our bodys complex detoxification systems.

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Effects Of 1252d3 On Emt And Metastasis

In total, 20â30% of patients with early-stage BC develop metastatic disease. The most common site of metastatic lesions for BC is bone, followed by brain, liver and lung. However, which organ is affected by BC metastasis is highly dependent on the BC subtype .

Tumoural VDR expression is reported to protect against BC metastasis in an orthotopic transplantation model of murine 168FARN BC cells, in which Vdr expression was silenced with shRNA. Tumours from Vdr KD cells not only grew significantly faster than tumours from control or Vdr rescue cells but also metastasized to the liver. Gene analysis identified Id1 as a direct mediator of VDR signalling in murine BC cells, and this relationship was confirmed in humans .

An association between vitamin D signalling and the EMT process was demonstrated by the finding that the EMT-TF SLUG, member of the SNAIL zinc finger family, repressed the VDR gene in human BC cells, and reduced their sensitivity to the anti-tumour activity of 1,252D3. Indeed, introduction of SLUG expression in MDA-MB-468 and MCF7 cells resulted in significant reduction of VDR levels. Moreover, the invasive TNBC BT549 cell line has a high SLUG expression, whereas VDR is not expressed .

Research Table: Vitamin D And Breast Cancer Risk

Clinically sufficient vitamin D levels at breast cancer diagnosis and survival outcomes
This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, its important to understand some key concepts. Learn how to read a research table.

Introduction: Whether or not vitamin D is linked to a decreased risk of breast cancer is under study.

Most of the vitamin D a person gets comes from the sun and a small amount comes from their diet.

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Vitamins And Minerals In Supplements

Your doctor may recommend certain vitamins and supplements to help you stay healthy after treatment.

Calcium.Chemotherapy can weaken your bones. A calcium supplement with vitamin D, which helps your body absorb calcium, may protect your bones from changes due to treatment.

Multivitamin. A regular multivitamin may help you get essential vitamins and minerals to improve your overall health.

Probiotics. Probiotics help boost immunity, says Tara Scott, MD, a womens health specialist in Akron, OH. This may help you stay healthy after your treatment. Probiotics have anti-inflammatory effects, which may help protect against cancer. But there isnt enough research yet to know for sure.

Vitamin D. Experts say theres a link between low levels of vitamin D and breast cancer. Theres no evidence a vitamin D supplement will lower your risk of recurrence, but your doctor may recommend it for your overall health.


Overall Survival According To Clinicopathological Factors And Vitamin D Groups

Among clinicopathological factors, pre-perimenopausal status, luminal types, and four groups were associated with worse OS in univariate analysis . In the multivariate analysis, four groups were adjusted for age, because there was an imbalance between the four groups. Accordingly, pre-perimenopausal status, triple negative luminal types and 25 D groups had a statistically independent effect on OS. Among the four groups, only group 2, defined as initial insufficient 25D level and insufficient after supplementation, showed worse OS than group I . If sufficient 25D levels were achieved after vitamin D replacement in patients who had insufficient 25D levels at baseline, better OS was obtained, as in patients who had sufficient 25D level at baseline .

0.8410.6 0.091
  • Group 1: adequate 25D level at baseline and follow-up Group 2: insufficient levels of 25D initially and insufficient after supplements Group 3: insufficient initially, but adequate 25D levels after supplementation Group 4: adequate 25D levels in the beginning but insufficient in follow-up. IDC: invasive ductal carcinoma ILC: invasive lobular carcinoma. OR: odds ratio, CI: confidence interval. Multivariate analysis was performed for 25D level groups, luinal types, age, and menopausal status. Menopausal status and age were included because there was imbalance among 25D level groups as was shown in Table 1. Values in italic are p < 0.05 statistically significant values.

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    A Practical Alternative To Estrogen

    This study suggests that vitamin D supplementation may be a practical alternative to estrogen-lowering drugs for overweight and obese women to reduce their breast cancer risk, McTiernan said.

    âMedications to lower blood estrogens, such as aromatase inhibitors, reduce the risk of developing breast cancer in women at increased risk, but those medications are expensive and can have adverse effects,â she said. âSo itâs important to identify other ways to safely lower blood estrogens for all women.

    âWeâve shown in the past that weight loss significantly lowers blood estrogens. Now we know that vitamin D can add to that, but only if a woman takes enough of it to increase her vitamin D blood levels to a normal range,â she continued.

    The optimal circulating range of vitamin D is thought to be between 20 and 50 ng/ml. Blood levels lower than that may be inadequate for bone health and levels higher than that are associated with potential adverse effects, such as an increased risk of kidney stones.

    There is no consensus, however, regarding the optimal blood level of vitamin D necessary for lowering sex hormones, Mason said. âWe saw benefit for the women whose levels increased the most, but we donât know whether we might have seen even more benefit had the women taken more vitamin D or had increased their blood levels to a higher threshold.â


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